Cold Plasma in Cancer: Clinical Update

October 1, 2025

Understanding Cancer and Treatment Challenges

Current Cancer Treatment Landscape

Standard oncology practice relies on four primary modalities: surgical resection, systemic chemotherapy, radiation therapy, and immunotherapy. Despite decades of refinement, these approaches face fundamental limitations constraining treatment success^[4]. Systemic toxicity from chemotherapy affects healthy rapidly-dividing cells alongside cancer, causing myelosuppression, nausea, alopecia, neuropathy, and organ damage in the majority of patients. Radiation therapy accumulates tissue damage limiting cumulative doses and carries 1-5% lifetime risk of secondary malignancies.

Critical challenges include:

Local regional recurrence (LRR) representing primary failure mechanism for solid tumors after surgery
Microscopic residual disease at surgical margins impossible to visualize intraoperatively
Drug resistance development through cancer stem cell populations and genetic evolution
Deep tissue tumor penetration difficulties with topical or injected therapies
Quality of life deterioration from treatment side effects (hair loss, immunosuppression, fatigue)

Approximately 65% of solid tumor resections leave residual microscopic cancer cells at surgical margins, contributing directly to LRR and poor survival outcomes^[2]. This represents the unmet medical need cold plasma technology specifically addresses through intraoperative margin treatment.

Unmet Medical Needs in Oncology

The cancer treatment landscape requires selective therapies eliminating malignant cells while preserving healthy tissue function. Drug-resistant cancer cells—particularly cancer stem cells with slow proliferation rates—evade conventional chemotherapy designed targeting rapidly dividing populations. Advanced or recurrent solid tumors offer limited therapeutic options beyond palliative care once first-line treatments fail.

Economic burden reaches staggering proportions:

Annual US cancer treatment costs: $150-$200 billion
Individual patient expenses: $50,000-$200,000+ for chemotherapy regimens
Long-term care and monitoring: ongoing imaging, laboratory testing, supportive medications
Productivity losses: inability to work during toxic chemotherapy cycles
Healthcare system strain: emergency visits, hospitalizations for treatment complications

One pioneering technology addressing these challenges is cold atmospheric plasma. The Mirari Cold Plasma system, developed by General Vibronics and commercialized by Mirari Doctor, applies this fourth state of matter for therapeutic applications. While primarily developed for wound care, dermatology, and pain management, the underlying plasma technology shares mechanistic principles with oncology applications—generating controlled reactive species that modulate cellular responses.

What Is Cold Plasma in Cancer Treatment?

Definition and Scientific Principles

Cold atmospheric plasma represents ionized gas generated at ambient atmospheric pressure maintaining temperatures below 40°C—safe for direct tissue contact^[1]. This fourth state of matter (beyond solid, liquid, gas) achieves partial ionization through electrical discharges including dielectric barrier discharge (DBD), plasma jets, and atmospheric pressure devices. The technology produces energetic electrons and ions while keeping bulk gas temperature near room level.

The critical distinction from thermal plasma used in industrial cutting/welding applications lies in non-equilibrium conditions. Electron temperatures exceed 10,000K (approximately 1 eV) while neutral gas atoms remain at 35-40°C. This temperature differential enables direct application to living tissue without burns or thermal damage.

Generation methods include:

Plasma jets: directed streams of ionized gas from handheld devices (Canady Helios, kINPen)
Dielectric barrier discharge: alternating current across insulating materials creating uniform surface treatment
Atmospheric pressure systems: operation at normal pressure (760 Torr) eliminating vacuum requirements
Microwave-induced plasma: electromagnetic energy at 2.45 GHz for electrode-free generation

How Cold Plasma Kills Cancer Cells

Cold atmospheric plasma induces cancer cell death through multiple coordinated mechanisms creating synergistic anti-tumor effects^[1]. The primary driver involves reactive oxygen and nitrogen species (RONS) generation—hydrogen peroxide (H₂O₂), hydroxyl radicals (OH), nitric oxide (NO), peroxynitrite (ONOO⁻), and superoxide (O₂⁻).

Mechanism	Cellular Target	Effect	Selectivity Basis
RONS Generation	DNA, proteins, lipids	Double-strand breaks, oxidation	Cancer cells near oxidative stress threshold
Mitochondrial Disruption	Energy production	Cytochrome C release, ATP depletion	Higher baseline ROS in cancer mitochondria
Membrane Damage	Cell membranes	Permeability increase, ion dysregulation	Elevated aquaporin expression (24-48% more)
Electromagnetic Fields	Membrane potential	Action potential disruption	Altered ion channels in malignant cells

Multiple cell death pathways activate simultaneously^[3]:

Apoptosis: Programmed cell death through caspase activation and DNA fragmentation
Ferroptosis: Iron-dependent lipid peroxidation overwhelming cellular defenses
Pyroptosis: Inflammatory programmed death releasing danger signals
Necrosis: Direct cellular rupture in heavily damaged areas
Immunogenic cell death (ICD): Release of damage-associated molecular patterns (DAMPs) activating immune system

Recent 2025 research identified short-lived molecules—particularly peroxynitrite—as key drivers penetrating several millimeters into tumor tissue^[5]. This breakthrough contradicts previous beliefs that hydrogen peroxide alone mediated effects, expanding potential applications to deeper tissue masses.

Why Cancer Cells Are More Vulnerable Than Healthy Cells

The remarkable selectivity—3 to 10 times greater toxicity to malignant versus normal cells—stems from fundamental biological differences between cell populations^[3]. Cancer cells operate near oxidative stress thresholds due to elevated baseline reactive oxygen species from robust metabolic activity (Warburg effect). Additional ROS stress from plasma treatment overwhelms compromised antioxidant defenses.

Cancer cell vulnerabilities:

Elevated baseline ROS: 2-5 times higher than normal cells from altered metabolism
Weaker antioxidant systems: Lower glutathione, catalase, superoxide dismutase (SOD) levels
Increased aquaporin expression: Facilitates 24-48% faster H₂O₂ cellular uptake
Higher proliferation rates: Rapidly dividing cells more sensitive to oxidative damage
Altered mitochondria: Dysfunctional electron transport chains more vulnerable to disruption
p53 status: Wild-type p53 cells more sensitive; mutated p53 shows resistance

Healthy cells maintain stronger antioxidant buffers providing protection against transient ROS exposure. Lower proliferation rates and intact DNA repair mechanisms enable recovery from sub-lethal oxidative stress. This therapeutic window allows effective cancer treatment while preserving surrounding normal tissue—a critical advantage over chemotherapy and radiation causing indiscriminate cellular damage.

Types of Cancer Treated with Cold Plasma

Solid Tumors with Clinical Evidence

The FDA Phase I clinical trial established cold plasma efficacy across multiple solid tumor types^[2]. Twenty patients with stage IV or recurrent advanced cancers received intraoperative Canady Helios Cold Plasma (CHCP) treatment at surgical margins following tumor resection.

Clinical trial tumor types and results:

Breast cancer: Triple-negative and other subtypes; R0 patients achieved 69% overall response rate with 86% survival at 28 months
Ovarian cancer: Peritoneal dissemination cases; R0-MPM (microscopic positive margins) patients demonstrated 100% response rate
Colon/colorectal cancer: Exceptional local regional recurrence control preventing disease return at surgical sites
Lung cancer: Non-small cell carcinoma (NSCLC) showing apoptosis induction and tumor shrinkage
Sarcoma: Myxofibrosarcoma and other subtypes responding to margin treatment

Plasma-activated medium (PAM)—solutions irradiated with plasma acquiring anti-cancer properties—enables treatment of deeper or surgically inaccessible tumors. Melanoma, pancreatic cancer, and glioblastoma show promising responses in preclinical and early clinical investigations. For comprehensive information on cold plasma applications, visit cold plasma in cancer resources.

Tumor Characteristics Predicting Response

Not all cancers respond equally to cold plasma treatment. Understanding predictive biomarkers helps identify optimal candidates and personalize treatment approaches^[3].

Better CAP response associated with:

Higher tumor proliferation rates (Ki-67 >30%)
Wild-type p53 gene status (not mutated)
Elevated baseline intracellular ROS levels
Increased aquaporin expression on cell membranes
Accessible tumor location for direct plasma application

Resistance factors include:

p53 gene mutations (found in 50% of human cancers)
Lower proliferation rates (<10% Ki-67)
Strong antioxidant enzyme expression
Deep tissue location without PAM access
Prior extensive chemotherapy/radiation potentially altering cellular responses

Biomarker development represents active research priority. Measuring baseline ROS levels, antioxidant enzyme expression, and proliferation markers may predict treatment response before initiating therapy.

Clinical Evidence and FDA Trial Results

FDA-Approved Phase I Clinical Trial

The landmark first-in-human cold plasma oncology trial (NCT04267575) enrolled 20 patients with stage IV or recurrent solid tumors between March 2020 and April 2021^[2]. All patients underwent surgical tumor resection followed immediately by intraoperative CHCP treatment of surgical margins—tissue directly adjacent to where tumors were removed.

Safety outcomes exceeded expectations:

Zero CHCP-related adverse events in all 20 patients
No impact on vital signs: Blood pressure, heart rate, oxygen saturation unchanged (p>0.05)
Selective cancer cell death: Histological analysis confirmed healthy tissue preservation
No secondary malignancies: 28-31 month follow-up showed no new cancers
Well-tolerated: Patients with advanced stage IV disease completed treatment without complications

Efficacy results at 26-28 months demonstrated exceptional outcomes:

Patient Group	Overall Response Rate	Survival at 28 Months	Key Finding
R0 (clean margins)	69%	86%	Far exceeded historical 40-60% survival
R0-MPM (microscopic positive margins)	100%	40%	Complete response preventing recurrence
All patients (n=20)	Variable	24% at 31 months	Stage IV advanced disease population

The trial definitively established CHCP treatment as safe, selective for cancer cells, and achieving exceptional local regional recurrence control—addressing the primary cause of treatment failure in solid tumors^[2]. These results support progression to Phase II efficacy trials currently underway.

Recent Research Breakthroughs (2024-2025)

Multiple 2025 publications advanced understanding of cold plasma mechanisms and clinical applications^[1]^[5]. German researchers at Leibniz Institute for Plasma Science developed 3D hydrogel tissue models mimicking real tumor architecture, enabling precise observation of molecular penetration depths.

Key 2025 discoveries:

Deep tissue penetration: Short-lived peroxynitrite molecules penetrate several millimeters into solid tumors—far deeper than previously believed possible
Hydrogen peroxide secondary role: Removing H₂O₂ from plasma treatment maintained strong anti-cancer effects, contradicting earlier assumptions
Low-dose efficacy: Even minimal plasma exposure slows tumor growth by damaging mitochondria and disrupting energy production
Triple-negative breast cancer: Helium and argon plasma induce apoptosis, reduce tumor size 50-80%, and increase survival in animal models
Ferroptosis pathway: PAM induces iron-dependent cell death providing alternative mechanism overcoming apoptosis resistance

These breakthroughs expand cold plasma applications to previously unreachable deep tissue tumors and provide mechanistic understanding supporting device optimization.

Treatment Process and Clinical Protocols

Direct CAP Treatment Protocol

Intraoperative cold plasma application follows standardized protocols established during FDA Phase I trial^[2]. Treatment occurs in operating rooms under sterile conditions after surgical tumor removal.

Pre-treatment preparation includes:

Tumor margin identification and marking by surgeon
Sterile field maintenance throughout procedure
General or local anesthesia as needed for primary surgery
Device preparation: Canady Helios or kINPen systems
Photography for documentation and research analysis

Application technique specifications:

Plasma jet positioning: 1-5mm distance from tissue surface
Treatment duration: 30 seconds to 5 minutes per site depending on tumor size and location
Surface temperature monitoring: maintains <40°C preventing thermal damage
Systematic coverage: ensuring complete margin exposure including areas not visually suspicious
Vital signs monitoring: continuous blood pressure, heart rate, oxygen saturation assessment

The procedure adds 15-30 minutes to standard surgical time. No additional hospital stay required beyond normal post-surgical recovery. Patients typically resume activities within standard surgical recovery timeframes.

Plasma-Activated Medium (PAM) Treatment

For tumors inaccessible to direct plasma application—brain tumors, peritoneal dissemination, deeply embedded masses—plasma-activated medium offers indirect treatment approach^[1]. Solutions (saline, cell culture media, buffers) undergo plasma irradiation for 3-10 minutes, acquiring anti-cancer properties lasting hours to days.

PAM preparation and delivery:

Plasma irradiation of sterile saline or specialized media
Quality control: H₂O₂ concentration 0.5-2.0 mM, nitrite 50-200 μM (optimal therapeutic ranges)
Storage: refrigerated use within 2-48 hours depending on formulation stability
Delivery routes: intratumoral injection, intrathecal (brain/spinal), intraperitoneal (abdominal cavity), intravenous infusion
Dosing: volume and concentration calculated based on tumor size (typically 10-50 mL for localized treatment)

PAM treatment requires specialized training and facilities but enables cold plasma therapy for patients with surgically inaccessible disease. Clinical trials investigate PAM for glioblastoma, peritoneal carcinomatosis, and metastatic melanoma with encouraging preliminary results.

Safety Profile and Side Effects

Clinical Safety Data

The FDA Phase I trial and subsequent research establish cold plasma as remarkably safe compared to conventional cancer therapies^[2]. Zero treatment-related serious adverse events occurred across 20 patients with advanced stage IV disease—a population typically experiencing significant treatment complications.

No impact on physiological parameters:

Blood pressure remained stable (p>0.05 comparing pre/post-treatment)
Heart rate unchanged throughout procedures
Oxygen saturation maintained at baseline
No bleeding, infection, or wound healing complications at treatment sites
No systemic symptoms: nausea, fatigue, immunosuppression absent

Histological analysis of treated tissues confirmed selective cancer cell death while healthy cells remained intact. Long-term follow-up spanning 28-31 months identified no secondary malignancies or delayed adverse effects attributable to plasma treatment.

Comparison with Conventional Therapy Side Effects

The safety advantage becomes most apparent comparing cold plasma with standard oncology treatments. Chemotherapy causes severe side effects in 60-90% of patients including myelosuppression (requiring blood transfusions), nausea/vomiting (despite antiemetics), alopecia (complete hair loss), peripheral neuropathy (permanent in some cases), and organ toxicity (cardiac, renal, hepatic damage).

Side effect comparison:

Treatment Modality	Severe Side Effects	Systemic Toxicity	Recovery Time	Quality of Life Impact
Cold Plasma	<5% (mild redness)	None	Immediate	Minimal
Chemotherapy	60-90%	Severe	Weeks-months	Major
Radiation	40-80%	Moderate	Weeks-months	Moderate-major
Surgery Alone	10-30%	None	Days-weeks	Mild-moderate

Radiation therapy causes acute toxicity (skin burns, mucositis) and chronic effects (fibrosis, secondary cancers developing years later). Cold plasma eliminates these risks through localized, non-thermal treatment preserving surrounding tissue.

FDA Approval Status and Regulatory Landscape

Current FDA Status

The Canady Helios Cold Plasma device received FDA approval for the first Phase I clinical trial in cancer treatment during 2019-2020^[6]. Trial completion (April 2021) demonstrated safety and promising efficacy, supporting progression to Phase II studies.

Regulatory timeline:

2019: FDA Investigational Device Exemption (IDE #190165) granted
March 2020: Patient enrollment initiated at Rush University Medical Center and Sheba Medical Center
April 2021: Phase I trial completion with 20 patients
July 2023: Full results published in peer-reviewed journal Cancers
2024-2025: Phase II trials underway for specific tumor types
Projected 2027-2030: 510(k) clearance anticipated for specific indications based on Phase II/III data

Current status classifies cold plasma as investigational medical device for cancer treatment. Patients access therapy through clinical trial enrollment at participating institutions. Full FDA approval for routine clinical use requires additional Phase II/III randomized controlled trials demonstrating efficacy across larger patient populations.

Global Regulatory Approvals

European markets demonstrate more advanced regulatory acceptance. The kINPen Med device holds CE marking for medical applications including wound care with potential oncology extensions^[3]. Germany, France, and Netherlands conduct multiple clinical trials investigating cold plasma across cancer types.

Asian markets—Japan, South Korea, China—pursue preclinical research and early clinical studies. Australia’s Therapeutic Goods Administration (TGA) evaluates plasma devices for various medical applications. International regulatory harmonization efforts through ISO standards development may accelerate global access.

Cost Analysis and Healthcare Economics

Treatment Cost Estimates

Cold plasma therapy offers substantial cost advantages over conventional cancer treatments. Device capital costs range $15,000-$75,000 for clinical-grade systems—comparable to many surgical instruments and far less than radiation therapy equipment ($1-5 million).

Per-treatment cost breakdown:

Device operation: $50-$200 (plasma generation, gas consumption)
Staff time: $200-$500 (surgeon, nurse, technician involvement)
Facility fees: $250-$1,300 (operating room time, sterilization, documentation)
Total per treatment: $500-$2,000

Course of treatment typically involves 5-15 sessions for solid tumor management (total $2,500-$30,000) versus chemotherapy regimens costing $50,000-$200,000+. Radiation therapy ranges $10,000-$50,000. Cold plasma represents 60-85% cost reduction compared to conventional multi-drug chemotherapy.

Additional cost savings accrue from eliminated hospitalizations for treatment complications, reduced emergency visits, preserved productivity (patients maintain work capacity), and decreased supportive medication requirements (anti-nausea drugs, growth factors, antibiotics).

Access to Cold Plasma Cancer Treatment in US

Current access remains limited to clinical trial participation at approximately 20 academic medical centers conducting FDA-approved studies. Major cancer centers with research programs include Rush University Medical Center (Chicago), Memorial Sloan Kettering (New York), MD Anderson (Houston), Mayo Clinic (Rochester), and Johns Hopkins (Baltimore).

Patient enrollment process:

Search ClinicalTrials.gov for “cold plasma cancer” identifying active studies
Review eligibility criteria: typically stage IV or recurrent solid tumors
Contact trial coordinators at participating institutions
Complete screening evaluations: imaging, laboratory tests, performance status assessment
Enrollment if eligible; treatment often provided at no cost through trial insurance

Geographic availability concentrates in major metropolitan areas currently. Expansion anticipated following FDA approval with eventual integration into community oncology practices projected 2028-2032 timeframe.

Key Takeaways

Cold plasma selectively kills cancer cells through multiple death pathways while sparing healthy tissue, achieving 3-10 times greater toxicity to malignant cells.
FDA Phase I trial demonstrated zero serious adverse events with 69-100% response rates and 86% survival at 28 months for resected tumors.
Treatment costs $500-$2,000 per session versus $50,000-$200,000 for chemotherapy, representing 60-85% cost savings with superior safety profiles.
Both direct plasma application and plasma-activated medium (PAM) enable treatment of accessible and deep tumors across multiple cancer types.
Current investigational status requires clinical trial enrollment; FDA approval projected 2027-2030 pending Phase II/III trial results.
No systemic side effects occur—no nausea, hair loss, or immunosuppression—enabling maintained quality of life during treatment.
Technology addresses critical unmet need: microscopic residual disease at surgical margins causing local regional recurrence in 65% of resections.

Frequently Asked Questions

How does cold plasma selectively kill cancer cells but not healthy cells?

Cancer cells have elevated baseline ROS levels, weaker antioxidant systems, and 24-48% higher aquaporin expression facilitating reactive species uptake^[3]. Additional oxidative stress from plasma overwhelms compromised defenses causing apoptosis. Healthy cells possess stronger antioxidant buffers and lower proliferation rates providing protection. Selectivity ratio reaches 3-10 times more toxic to malignant versus normal cells.

What types of cancer can be treated with cold plasma?

FDA Phase I trial demonstrated safety and efficacy for breast, ovarian, colon, lung cancer, and sarcoma^[2]. Preclinical evidence supports melanoma, pancreatic, liver, prostate, brain, cervical, and head/neck cancers. Best results occur with solid tumors having surgical access or amenable to PAM injection. Current focus targets advanced/recurrent cancers where conventional therapies failed.

Is cold plasma therapy FDA approved for cancer treatment?

FDA approved first Phase I clinical trial (2019-2020) using Canady Helios Cold Plasma device^[6]. Phase I trial completed April 2021 demonstrating safety and promising efficacy. Current status remains investigational—not FDA-approved for routine clinical use outside trials. Anticipated timeline: Phase II/III trials underway; full FDA approval projected 2027-2030 for specific indications. Patients access through clinical trial enrollment.

How effective is cold plasma compared to chemotherapy?

Phase I trial achieved 69-100% overall response rates in completely/microscopically resected tumors^[2]. Survival reached 86% at 28 months for R0 patients versus historical 40-60% with standard therapy. Exceptional local regional recurrence control addresses primary solid tumor failure mechanism. Advantages over chemotherapy include zero systemic side effects, no drug resistance, maintained quality of life, and 60-85% cost savings.

What are the side effects of cold plasma cancer treatment?

FDA Phase I trial reported zero treatment-related serious adverse events in 20 patients^[2]. Minimal effects include possible transient redness and mild warmth during application. No systemic toxicity occurs—no nausea, hair loss, immune suppression, or organ damage. Conventional chemotherapy causes severe side effects in 60-90% of patients. Safety profile proves superior to all existing cancer therapies.

How much does cold plasma cancer treatment cost?

Per-treatment costs $500-$2,000 including device operation and facility fees. Course of treatment totals $2,500-$30,000 for typical 5-15 session protocols. Chemotherapy regimens cost $50,000-$200,000+; radiation therapy $10,000-$50,000. Cost savings reach 60-85% versus conventional multi-drug chemotherapy. Current access primarily through clinical trials often provides treatment at no cost to qualifying patients.

Can cold plasma cure cancer or just slow it down?

Phase I trial demonstrated exceptional local regional recurrence control preventing cancer return at surgical sites^[2]. Complete responses documented in some patients with no evidence of disease at long-term follow-up. Survival reached 86% at 28 months in R0 patients (stage IV disease). Curative potential greatest for surgical margin treatment eliminating microscopic residual disease. Current positioning: fourth treatment modality complementing surgery, chemotherapy, radiation.

Where can I get cold plasma cancer treatment in the United States?

Clinical trial sites include 20+ academic medical centers conducting FDA-approved studies. Major cancer centers include Rush University Medical Center, Memorial Sloan Kettering, MD Anderson, Mayo Clinic, and Johns Hopkins. Trial enrollment requires searching ClinicalTrials.gov for “cold plasma cancer” identifying active studies. Geographic distribution concentrates in major metropolitan areas currently; expansion anticipated with FDA approval. Patient qualification: stage IV or recurrent solid tumors.

Is cold plasma treatment covered by insurance?

Current status involves limited coverage primarily through clinical trial insurance protocols. Medicare maintains investigational designation with potential Coverage with Evidence Development (CED) pathway. Private insurers conduct case-by-case evaluation requiring prior authorization. Clinical trials often provide treatment at no cost to qualifying patients. Future projections anticipate coverage expansion 2027-2030 with FDA approval and Phase II/III data.

How long does cold plasma treatment take and how many sessions are needed?

Single treatment duration spans 30 seconds to 5 minutes for direct plasma application. PAM injection requires similar time as standard injection procedures (minutes). Intraoperative CHCP adds 15-30 minutes to surgical procedures. Treatment frequency varies daily to weekly depending on protocol and cancer type. Total sessions typically range 5-15 treatments for solid tumor management; varies by indication and response.

References

Fang T, Chen Z, Chen G. (2025). Advances in cold atmospheric plasma therapy for cancer. Bioactive Materials. 53:433-458. https://pubmed.ncbi.nlm.nih.gov/40747454/
Canady J, Murthy SRK, Zhuang T, et al. (2023). The First Cold Atmospheric Plasma Phase I Clinical Trial for the Treatment of Advanced Solid Tumors: A Novel Treatment Arm for Cancer. Cancers. 15(15):3688. https://pmc.ncbi.nlm.nih.gov/articles/PMC10378184/
Holanda AGA, Sousa NVD, Gonçalves MPG, et al. (2025). Cold Atmospheric Plasma in Oncology: A Review and Future Perspectives. International Journal of Molecular Sciences. 26(7):3144. https://pmc.ncbi.nlm.nih.gov/articles/PMC11987927/
National Cancer Institute. (2025). Cancer Treatment. NIH National Cancer Institute. https://www.cancer.gov/about-cancer/treatment
Miebach L, Bekeschus S, et al. (2025). Cold plasma penetrates deep into tissue to fight cancer. Trends in Biotechnology. Medical Xpress. https://medicalxpress.com/news/2025-08-cold-plasma-penetrates-deep-tissue.html
Rush University Medical Center. (2020). Rush Performs Country’s First Ever Cold Plasma Adjuvant Therapy. Rush News. https://www.rush.edu/news/rush-performs-countrys-first-ever-cold-plasma-adjuvant-therapy