Modulated Electrohyperthermia: A New Hope for Cancer Patients

Table 1

Clinical trials that used mEHT in combination with other treatments.

No.	Tumor site	Number of patients	Treatment used	Results	Reference
1	Relapsed high-grade gliomas	15	mEHT + alkylating chemotherapy	Tolerable and safe for patients with relapses even with a high escalation of the dose.	[96]
2	Advanced gliomas	12	Chemotherapy + radiotherapy + mEHT	CR = 1, PR = 2, RR = 25%. Median duration of response = 10 m. Median survival = 9 m, 25% survival rate at 1 year.	[97]
3	Relapsed malignant gliomas	24	mEHT	Median survival = 19.5 m, 55% survival rate at 1 year, 15% at 2 years.	[98]
4	Advanced glioblastoma	60	mEHT + immunotherapy	No added toxicity by immunotherapy. Median progression-free survival (PFS) = 13 m. Median follow-up 17 m, median OS was not reached. Estimated OS at 30 m was 58%.	[87]
5	Various brain-gliomas	140	Chemotherapy + radiotherapy + mEHT	OS = 20.4 m. mEHT was safe and well tolerated.	[99]
6	High-grade gliomas	179	mEHT + radiotherapy + chemotherapy	Longstanding complete and partial remissions after recurrence in both groups.	[100]
7	Glioblastoma & astrocytoma	149	mEHT + radiotherapy + chemotherapy (BSC, palliative range)	5 y-OS = 83% (AST) in mEHT vs. 5 y-OS = 25% by BSC. 5 y-OS = 3.5% in mEHT vs. 5 y-OS = 1.2% by BSC for GBM. Median OS = 14 m of mEHT for GBM and OS = 16.5 m for AST.	[101]
8	Advanced hepatocell. carcinoma	21	Chemotherapy + mEHT	PR = 1, CR = 0, SD = 11. Combined therapy was effective, and no major complications were observed.	[102]
9	Refractory hepatocell. carcinoma	22	mEHT + thermo-active agents (TAA) or mEHT without TAA	CR = 1, PR = 0. Median OS = 20.5 weeks. 50% showed evidence of increasing QoL and minimal toxicity.	[103]
10	Small-cell lung cancer (SCLC)	22	Chemotherapy + mEHT	mEHT-enhanced destruction of the cancer cells. Improved the OS of patients, too.	[104]
11	Advanced cervical cancer	236	Random. Phase III chemoradiation alone CHR and mEHT group (mEHT + CHR) [preliminary data]	Preliminary data for the first 100 participants. A positive trend in survival and local disease control by mEHT. No significant differences in acute adverse events or QoL between the groups.	[105]
12	Advanced cervical cancer	38	Chemotherapy ± mEHT	The overall response (CR + PR + SD vs. PD) was significantly greater with mEHT. No complications or extra adverse effects by mEHT.	[106]
13	Advanced cervical cancer	72	Radiotherapy + chemotherapy + mEHT	CR + PR = 73.5%, SD = 14.7%. The addition of mEHT increased the QoL and OS.	[107]
14	Advanced cervical carcinoma	20	mEHT + radiotherapy + chemotherapy	mEHT increased the peritumor temperature and blood flow in human cervical tumors, promoting the radiotherapy + chemotherapy.	[55]
15	Advanced cervical carcinoma	108	mEHT + chemoradiotherapy	The complete metabolic response (CMR) of disease outside the radiation field at 6 m posttreatment shows the abscopal effect, significantly associated with the addition of mEHT.	[82]
16	Advanced cervical carcinoma	206	Random. Phase III chemoradiation alone [108] and mEHT group (mEHT + CHR) [preliminary data]	Compliance to mEHT treatment was high (97% completed ≥8 treatments) with no significant differences in CRT-related toxicity between treatment groups or between HIV-positive and HIV-negative participants.	[86]
17	Advanced cervical carcinoma	202	mEHT + chemoradiotherapy	Six-month local disease-free survival (LDFS) = 38.6% for mEHT and LDFS = 19.8% without mEHT (). Local disease control (LDC) = 45.5% with mEHT LDC = 24.1% without mEHT; ().	[85]
18	Stage III-IV NSCLC	15	Ascorbic acid (AA) infusion + mEHT	AA safely synergises with mEHT and was well tolerated with no major adverse effects.	[109]
19	Advanced NSCLC	97	mEHT + radiotherapy + chemotherapy	Median OS = 9.4 m with mEHT OS = 5.6 m without mEHT; (). Median PFS = 3 m for mEHT and PFS = 1.85 m without mEHT; .	[110]
20	Advanced NSCLC	311 (61 + 197 + 53)	Radiotherapy + chemotherapy + mEHT	Two centres PFY (), HTT (), control (). 80% (PFY), 80% (HTT) had distant metastases, conventional therapies failed. Median OS = 16.4 m (PFY), 15.6 m (HTT), 14 m (control); first-year survival 67.2% (PFY), 64% (HTT), 26.5% (control).	[89, 111]
21	Advanced NSCLC	44	Chemotherapy + ketogenic diet + hyperbaric oxygen + mEHT	Mean OS = 42.9 m, PFS = 41 m. No problems were encountered due to fasting, hypoglycemia, ketogenic diet, mEHT, or hyperbaric oxygen therapy.	[112]
22	Peritoneal carcinomatosis with malignant ascites	260	mEHT + traditional Chinese medicine (TCM) compared to intraperitoneal chemoinfusion [19]	The objective response rate (OPR) = 77.7% in study group (mEHT + TCM) vs. OPR = 63.8% in the ICI group. The QoL = 49.2% vs. 32.3% in the active and control group. Adverse effect rate (AER) = 2.3% vs. 12.3%.	[113]
23	Advanced rectal cancer	76	mEHT + radiotherapy + chemotherapy	Downstaging + tumor regression, ypT0, and ypN0 was better with mEHT than without. No statistical significance.	[114]
24	Liver metastasis from colorectal cancer	80	Chemotherapy + mEHT	Median OS = 24.5 m, and expected (historical) OS = 11 m.	[115]
25	Various types of sarcoma	13	Radiotherapy + chemotherapy + mEHT	Primary, recurrent, and metastatic sarcomas responded to mEHT. The masses regressed.	[116]
26	Soft tissue sarcoma	24	Chemotherapy + mEHT	Pathological response rate (pRR) = 42% in neoadjuvant chemo-hyperthermia treatment median OS = 31 m.	[117]
27	Advanced pancreas carcinoma	25	mEHT + chemotherapy + ketogenic diet + oxygen therapy	Mean follow-up = 25.4 m, median OS = 15.8 m, median PFS = 15.8 m.	[118]
28	Advanced pancreas carcinoma	26	Chemotherapy + mEHT	SD = 9 (48%), PR = 4 (21%) PD = 6 (31%).	[119]
29	Advanced pancreas	106	mEHT + radiotherapy + chemotherapy	After 3 m, PR = 22 (64.7%), SD = 10 (29.4%), PD = 2 (8.3%) with mEHT after 3 m of the therapy. In group without mEHT in the same time: PR = 3 (8.3%), SD = 10 (27.8%), PD = 23 (34.3%). The median OS = 18 m with mEHT and OS = 10.9 m without mEHT.	[101]
30	Advanced pancreas carcinoma	20	Enzyme-therapy + immunolo-modulation + hormone therapy + mEHT	. Most patients experienced partially excellent improvement of QoL.	[55]
31	Advanced pancreas carcinoma	133 ()	Radiotherapy + chemotherapy + mEHT	Two centres PFY (), HTT (), control (). 59% (PFY), 88% (HTT) had distant metastases, conventional therapies failed. Median OS = 12.0 m (PFY), 12.7 m (HTT), 6.5 m (control); first-year survival 46.2% (PFY), 52.1% (HTT), 26.5% (control). QoL was improved.	[120]
32	Ovarian cancer	19	mEHT with dose escalation	The mEHT treatment was feasible in patients with recurrent or progressive ovarian cancer without any complications.	[121]
33	Metastatic cancers (colorectal, ovarian, breast)	23	mEHT + radiotherapy + chemotherapy	OS and time to progression (TTP) were influenced by the number of chemotherapy cycles () and mEHT sessions (). Bevacizumab-based chemotherapy with mEHT had a favourable tumor response, was feasible and well-tolerated in metastatic cancer patients.	[122]
34	Different types of metastatic/recurrent cancers	33	mEHT + radiotherapy	CR = 2 (6.1%), very good PR = 5 (15.2%), PR = 13 (39.4%), SD = 9 (27.3%), PD = 4 (12.1%). Three patients (9.1%) developed autoimmune toxicities. All three patients had long-lasting abscopal responses outside the irradiated area.	[93]
35	Advanced gastric cancer	24	mEHT + chemotherapy + ketogenic diet + oxygen therapy	CR = 22 (88%). Mean follow-up = 23.9 m, mean OS = 39.5 m, mean PFS = 36.5 m.	[123]