WO2025008440A1

WO2025008440A1 - Electric field therapy

Info

Publication number: WO2025008440A1
Application number: PCT/EP2024/068812
Authority: WO
Inventors: Christopher Bullock; Ashwin Narayanan; Jinwei ZHAO; Oluwatomisin OLUKOGA
Original assignee: QV Bioelectronics Ltd
Current assignee: QV Bioelectronics Ltd
Priority date: 2023-07-05
Filing date: 2024-07-04
Publication date: 2025-01-09
Anticipated expiration: 2026-01-05
Also published as: AU2024289516A1; GB2631521A; CN121444171A; GB202310323D0

Abstract

A method for improving electric field therapy for delivering to a patient with a tumor, wherein the regimen parameters are selected for the profile of the tumour. Also described are methods of electric field therapy, methods for treating tumours employing electric field therapy, and devices programmed to deliver electric field therapy regimens.

Description

ELECTRIC FIELD THERAPY

FIELD

The present specification relates to electric field therapy. More specifically the present specification relates to a method of improving electric field therapy for administering to a patient with a tumour employing regimen parameters selected for the profile of the tumour.

BACKGROUND

Electric field therapy (EFT), sometimes referred to as electrotherapy, involves the use of electrical energy in medical treatment and can apply to a variety of treatments, including the use of electrical devices such as deep brain stimulators (DBS) for neurological disease such as Parkinson's disease. Electric field therapy can also be used as a physical therapy for muscle stimulation, pain management and wound healing for example, and may be used for the treatment of psychological symptoms for example anxiety, insomnia, depression, hypervigilance, and obsessive compulsive disease.

Electric field therapy, typically involving the use of an electrical waveform in order to generate low-intensity electric fields alternating at an intermediate frequency (generally 10 to 600 kHz) using electric field of strength (E) ~ 1-5 Vcm^-1, is currently being investigated as a treatment modality for several types of solid malignant tumours including lung cancer, liver cancer, gastric cancer, pancreatic cancer, malignant pleural mesothelioma and ovarian cancer. Electric fields are believed to interfere with mitosis, where dipole molecules like tubulin dimers of microtubules align with the applied field leading to improper polymerization and early metaphase exit. Furthermore, cells in the final stage of mitosis (telophase) are subject to non-uniform E that create dielectrophoretic (DEP) forces moving particles toward the furrow, prompting DNA damage and cellular suicide. (Jenkins et al.; Adv. Sci.2021,8, 2100978; https://doi.org/10.1002/advs.202100978). Electric field therapy has also been employed in combination with chemotherapy.

Electric field therapy has been demonstrated clinically to be an effective treatment for glioblastoma (GBM) (previously glioblastoma multiforme), the most common type of primary brain tumours in adults. In phase III multi-centre clinical trials, electric field therapy has been shown to increase patient overall survival to 21 months when used as an addition to surgery (for example surgical resection), chemotherapy and radiotherapy (Stupp et al.; JAMA; 2017; 318(23):2306-16; doi: 10.1001/jama.2017.18718.). The electric field therapy delivers alternating sinusoidal electrical fields at specific frequencies (50 - 300 kHz) to the head slowing the growth of recurrent tumours and extending patient survival (Kirson et al.; PNAS; 2007; 104(24):10152-7; doi:10.1073/pnas.0702916104). Malignant tumours have highly diverse profiles both at the inter-tumour level (between different tumours) and intra-tumour level (within the same tumour) including within the tumour microenvironment itself. Regional differences within the tumour impose different selective pressures on tumour cells, leading to a wider spectrum of dominant subclones in different spatial regions of the tumour. Tumours may exhibit a combination of genetic, epigenetic, molecular and/or transcriptomic variabilities: genetic variability is either the presence of, or the generation of, genetic differences; epigenetic variation refers to modifications to DNA that do not alter the underlying nucleotide sequence, but can influence behaviour, morphology, and physiological phenotypes by affecting gene expression and protein synthesis; molecular variability is the changes in the nucleic acids (DNA/RNA) and/or proteins as well as in their interactions, which can affect the biological activity within a cell and/or tissue; and transcriptomic variability refers to the to changes in gene expression dues to changes in the RNA molecules which includes protein coding (mRNA) as well as non-coding RNAs produced in a particular cell or tissue. Tumour variability introduces significant challenges for effective drug treatment strategies.

Traditionally, glioblastoma has been categorised according to three molecular subtypes; proneural, classical, and mesenchymal with many patients exhibiting multiple subtypes within the same tumour. Variability increases with time, and not only can more than one subtype be found within the same tumour at the same time, but they may also occupy spatially distinct regions. In multiple biopsies taken from the same tumour, the proneural subtype was predominantly found at the leading edge and in regions of invasion, whilst the mesenchymal subtype was mostly found in more hypoxic regions such as pseudopalisades or the necrotic core (Heiland et al, Mol. Cancer Res. 2018, 16, 655). This heterogeneity of glioblastoma adds to the complexity of treatment and poor overall survival times.

The present inventors have found that different tumour profiles react differently to different electric field therapy regimens, where the regimen involves for example the selection of parameters including the frequency, amplitude (current or voltage), electric field strength, direction of the current, and/or duration of treatment. Altering one or more of these parameters can change the biological effect seen in cancer cells through the activation of various signalling pathways. For therapeutic purposes, it is desirable to cause the death of cancer cells or inhibition of their division as this will have a beneficial effect on patient survival. The present inventors have found that the response of an individual patient's tumour to a set of treatment regimen parameters can depend on the profile of the tumour, for example the genetic and/or epigenetic and/or molecular and/or transcriptomic profile of the tumour. It is therefore possible to optimise and improve the therapeutic effect of the regimen through the selection of parameters with respect to the profile of the tumour. The optimal parameters may alter with respect to time during the course of treatment. SUMMARY

This specification describes, in part, a method for improving electric field therapy for delivering to a patient with a tumor which comprises:

(i) receiving, by a processor of a computer system, a genetic and/or epigenetic and/or molecular and/or transcriptomic profile of the tumour;

(ii) generating an analysis of the tumour from the received data;

(iii) determining electric field therapy regimen parameters selected for the analysis of the tumour; and

(iv) configuring an electric field therapy device to deliver electric field therapy employing those parameters.

This specification also describes, in part, an electric field therapy device comprising a processor configured to deliver the electric field therapy treatment regimen generated by steps (i)-(iv) of the method for improving electric field therapy as described herein.

This specification also describes, in part, an electric field therapy device configured to deliver the electric field therapy treatment regimen generated by steps (i)-(iv) of the method for improving electric field therapy as described herein.

This specification also describes, in part, a computer system comprising a processor configured to perform steps (i)-( iv) of the method for improving electric field therapy as described herein.

This specification also describes, in part, a computer program comprising instructions which, when the program is executed by a computer, cause the computer to carry out steps (i )-( iv) of the method for improving electric field therapy as described herein.

This specification also describes, in part, a computer-readable storage medium comprising instructions which, when executed by a computer, cause the computer to carry out steps (i)-(iv) of the method for improving electric field therapy as described herein.

This specification also describes, in part, an electric field therapy regimen for administering to a patient with a tumour, wherein the regimen parameters are selected for the profile of the tumour.

This specification also describes, in part, a method of electric field therapy which comprises an electric field therapy regimen as described herein.

This specification also describes, in part, a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein.

This specification also describes, in part, electric field therapy for use in the treatment of a patient with a tumour wherein the electric field therapy comprises administering to the patient a therapeutically effective electric field therapy regimen as described herein. This specification also describes, in part, an electric field therapy device programmed to deliver an electric field therapy regimen as described herein.

DETAILED DESCRIPTION OF THE INVENTION

Many embodiments of the invention are detailed throughout the specification and will be apparent to a reader skilled in the art. The invention is not to be interpreted as being limited to any of the recited embodiments.

"A" means "at least one". In any embodiment where "a" is used to denote a given material or element, "a" may mean one.

"Comprising" means that a given material or element may contain other materials or elements. In any embodiment where "comprising" is mentioned the given material or element may be formed of at least 10% w/w, at least 20% w/w, at least 30% w/w, or at least 40% w/w of the material or element. In any embodiment where "comprising" is mentioned, "comprising" may also mean "consisting of" (or "consists of") or "consisting essentially of" (or "consists essentially of") a given material or element.

"Consisting of" or "consists of" means that a given material or element is formed entirely of the material or element. In any embodiment where "consisting of" or "consists of" is mentioned the given material or element may be formed of 100% w/w of the material or element.

"Consisting essentially of" or "consists essentially of" means that a given material or element consists almost entirely of that material or element. In any embodiment where "consisting essentially of" or "consists essentially of" is mentioned the given material or element may be formed of at least 50% w/w, at least 60% w/w, at least 70% w/w, at least 80% w/w, at least 90% w/w, at least 95% w/w or at least 99% w/w of the material or element.

In any embodiment where "is" or "may be" is used to define a material or element, "is" or "may be" may mean the material or element "consists of" or "consists essentially of" the material or element.

Claims are embodiments.

Electric field therapy

Electric field therapy (EFT) involves the use of electrical energy in medical treatment.

In one embodiment, the electric field therapy as described herein comprises an electric field therapy device (charge delivery device) which may be a stimulator/battery pack. In one embodiment the electric field therapy device may be surgically implanted. In one embodiment the electric field therapy device may be surgically implanted into the chest cavity. Suitable electric field therapy devices include implanted pulse generators (IPGs) for example those used in deep brain stimulation for the alleviation of Parkinson's Disease tremors.

In one embodiment there is provided an electric field therapy device programmed to deliver an electric field therapy regimen as described herein. In one embodiment there is provided an electric field therapy device comprising a processor configured to deliver the electric field therapy treatment regimen generated by steps (i)-(iv) of the method for improving electric field therapy as described herein.

In one embodiment there is provided an electric field therapy device configured to deliver the electric field therapy treatment regimen generated by steps ( i)-(iv) of the method for improving electric field therapy as described herein.

In one embodiment, the electric field therapy comprises at least one electrode.

In one embodiment the electric field therapy comprises non-implanted electrodes, e.g. transducer arrays, placed on the skin close to the tumour, e.g. by the Optune® apparatus.

In one embodiment the electric field therapy comprises multiple electrodes. These cooperating electrodes pass current between them, either in one direction under direct current conditions, or in both directions under alternating current conditions.

In one embodiment the electric field therapy comprises multiple implanted electrodes.

In one embodiment the electric field therapy comprises one or more implanted electrodes.

In one embodiment the electric field therapy comprises two implanted electrodes.

In one embodiment the electric field therapy comprises three implanted electrodes.

In one embodiment the electric field therapy comprises four implanted electrodes.

In one embodiment the electric field therapy comprises five implanted electrodes.

In one embodiment the electric field therapy comprises six implanted electrodes.

In one embodiment the electric field therapy comprises seven implanted electrodes.

In one embodiment the electric field therapy comprises eight implanted electrodes.

In one embodiment the electric field therapy comprises multiple electrodes implanted into the tumour or, following surgical resection, the tumour resection margin.

In one embodiment the electric field therapy comprises one electrode implanted into the tumour or, following surgical resection, the tumour resection margin.

In one embodiment the electric field therapy comprises two electrodes implanted into the tumour or, following surgical resection, the tumour resection margin.

In one embodiment the electric field therapy comprises three electrodes implanted into the tumour or, following surgical resection, the tumour resection margin.

In one embodiment the electric field therapy comprises four electrodes implanted into the tumour or, following surgical resection, the tumour resection margin.

In one embodiment the electric field therapy comprises five electrodes implanted into the tumour or, following surgical resection, the tumour resection margin.

In one embodiment the electric field therapy comprises six electrodes implanted into the tumour or, following surgical resection, the tumour resection margin. In one embodiment the electric field therapy comprises seven electrodes implanted into the tumour or, following surgical resection, the tumour resection margin.

In one embodiment the electric field therapy comprises eight electrodes implanted into the tumour or, following surgical resection, the tumour resection margin.

In one embodiment the electric field therapy comprises multiple external electrodes. An external electrode is an electrode that is not implanted.

In one embodiment the electric field therapy comprises one or more external electrodes.

In one embodiment the electric field therapy comprises two external electrodes.

In one embodiment the electric field therapy comprises three external electrodes.

In one embodiment the electric field therapy comprises four external electrodes.

In one embodiment the electric field therapy comprises five external electrodes.

In one embodiment the electric field therapy comprises six external electrodes.

In one embodiment the electric field therapy comprises seven external electrodes.

In one embodiment the electric field therapy comprises eight external electrodes.

In one embodiment the electric field therapy comprises a magnetic coil.

In one embodiment the electric field therapy comprises an injectable electrode, for example those described in WO 2022/184896 which is incorporated herein in its entirety.

In one embodiment the electric field therapy comprises an injectable electrode, for example those described in WO 2022/184896, injected into a tumour cavity following surgical resection.

In one embodiment the electric field therapy comprises a biphasic injectable electrode which comprises a plurality of solid particles and a transporter phase, wherein both the solid particles and the transporter phase comprise poly(3,4-ethylenedioxythiophene)polystyrene sulfonate.

In one embodiment the electric field therapy comprises a biphasic injectable electrode which comprises a plurality of solid particles and a transporter phase, wherein both the solid particles and the transporter phase comprise poly(3,4-ethylenedioxythiophene)polystyrene sulfonate, injected into a tumour cavity following surgical resection.

Regimen

A regimen, as used herein is a set of electric field therapy parameters to be delivered, i.e. suitable for delivery, to a patient for the electric field treatment of their tumour. The method for improving electric field therapy generates optimised regimen parameters selected for the analysis of the tumour. In one embodiment the regimen parameters remain constant during treatment. In one embodiment a regimen may involve cycling through sets of parameters over time during treatment. An electric field therapy device as described herein may be programmed with the regimen parameters and delivers the electric field therapy to the tumour, e.g. via electrodes. In one embodiment an electric field therapy regimen may be used in a method of electric field therapy.

Tumour

A tumour is a mass or group of abnormal cells that form in the body. It may be benign or malignant; and comprises the primary tumour, tumour resection margin, residual tumour, recurrent tumour, and/or tissue that might be reasonably suspected of containing tumour cells.

In one embodiment, the tumour is a solid tumour.

In one embodiment, the tumour is a malignant solid tumour.

In one embodiment, the tumour is:

• a brain tumour (including Grade I, II, III or IV glioma; pilocytic astrocytoma; subependymal giant cell astrocytoma; diffuse astrocytoma; oligodendroglioma; oligodendroglioma NOS; anaplastic astrocytoma; anaplastic oligodendroglioma; anaplastic oligodendroglioma NOS; glioblastoma; giant-cell glioblastoma; glioblastoma; subependymal giant cell astrocytoma; pilomyxoid astrocytoma; pleomorphic xanthoastrocytoma; ganglioglioma; oligoastrocytoma; meningiomas (including grade I, II or III meningioma and other neoplasms related to the meninges (for example haemangiopericytoma)); paediatric brain tumours (including ependymoma, medulloblastoma, atypical teratoid/rhabdoid tumour (AT/RT); choroid plexus papilloma; choroid plexus carcinoma; intracranial teratoma; and embryonal tumours with multilayered rosettes (ETMR)), pineal region tumours (for example pineoblastoma), pituitary region tumours (for example pituitary adenoma, craniopharyngioma, and chordoma), brain metastases or diffuse midline glioma;

• metastases of any cancer origin (for example brain metastasis including those from lung cancer, breast cancer, genitourinary tract cancer, osteosarcoma and melanoma);

• lung cancer (including mesothelioma, malignant pleural mesothelioma, non-small cell-lung cancer and small cell lung cancer)

• pancreatic cancer (for example locally advanced pancreatic adenocarcinoma);

• ovarian cancer (for example ovarian cancer resistant to chemotherapy);

• liver cancer (for example advanced hepatocellular cancer);

• breast cancer;

• cervical cancer;

• colorectal carcinoma;

• gastric cancer (including gastric adenocarcinoma);

• spinal nerve sheath tumours (including schwannoma, neurofibroma and ganglioneuroma);

• malignant melanoma;

• renal adenocarcinoma; or • urinary transitional cell carcinoma.

In one embodiment, the tumour is a brain tumour.

In one embodiment, the tumour is a Grade I, II, III or IV glioma.

In one embodiment, the tumour is a Grade I glioma.

In one embodiment, the tumour is pilocytic astrocytoma.

In one embodiment, the tumour is a Grade II glioma.

In one embodiment, the tumour is diffuse astrocytoma or oligodendroglioma.

In one embodiment, the tumour is a Grade III glioma.

In one embodiment, the tumour is anaplastic astrocytoma or anaplastic oligodendroglioma.

In one embodiment, the tumour is a Grade IV glioma.

In one embodiment, the tumour is diffuse midline glioma.

In one embodiment, the tumour is brain metastases.

In one embodiment, the tumour is giant-cell glioblastoma or glioblastoma.

In one embodiment, the tumour is glioblastoma.

In one embodiment, the tumour is recurrent glioblastoma.

In one embodiment, the tumour is a brain tumour that has been surgically resected.

In one embodiment, the tumour is a Grade I, II, III or IV glioma that has been surgically resected.

In one embodiment, the tumour is a Grade I glioma that has been surgically resected.

In one embodiment, the tumour is pilocytic astrocytoma that has been surgically resected.

In one embodiment, the tumour is a Grade II glioma that has been surgically resected.

In one embodiment, the tumour is diffuse astrocytoma or oligodendroglioma that has been surgically resected.

In one embodiment, the tumour is a Grade III glioma that has been surgically resected.

In one embodiment, the tumour is anaplastic astrocytoma or anaplastic oligodendroglioma that has been surgically resected.

In one embodiment, the tumour is a Grade IV glioma that has been surgically resected.

In one embodiment, the tumour is diffuse midline glioma that has been surgically resected.

In one embodiment, the tumour is brain metastases that has been surgically resected.

In one embodiment, the tumour is giant-cell glioblastoma or glioblastoma that has been surgically resected.

In one embodiment, the tumour is glioblastoma that has been surgically resected.

In one embodiment, the tumour is recurrent glioblastoma that has been surgically resected.

Regimen Parameters

In one embodiment regimen parameters comprise the frequency, amplitude (current or voltage), electric field strength, direction of the current, and/or duration of treatment, parameters. In one embodiment selecting, or determining, the regimen parameters comprises selecting, or determining, the frequency of the waveform ("frequency"). Altering the applied frequency may result in in differing biological effects between different tumour cell profiles. These varying biological effects include the activation of different signalling pathways which can be used to optimise cell death, inhibit mitosis or improve the efficacy of applied co-therapy. The frequency may be determined based on the tumour profile and can be a single frequency and/or a combination of multiple frequencies e.g. switched between a fixed time point.

In one embodiment selecting, or determining, the regimen parameters comprises selecting, or determining, the frequency wherein the frequency is between 10kHz - 600kHz.

In one embodiment selecting, or determining, the regimen parameters comprises selecting, or determining, the frequency wherein the frequency is between 100kHz - 500kHz.

In one embodiment selecting, or determining, the regimen parameters comprises selecting, or determining, the amplitude of the waveform ("amplitude"), which could be either current or voltage. There is a dose response whereby a certain amplitude may generate a particular biological effect. Where the target cancer cells are spatially distant from the stimulating electrodes, it is helpful to consider a particular electric field strength at the location of the cancer cells in 3D space. In this instance, the minimum amplitude required is that which generates the minimum electric field strength at the point location of the cancer cells in 3D space required to generate the desired biological effect. Increasing the applied amplitude beyond this activation level should proportionally increase the degree of biological effect generated. However, there is an upper limit on the amplitude that it would be desirable to deliver. This desirable window of amplitude is primarily limited at the upper end by concerns of patient safety as increasing amplitude may generate proportional increases in induced heating. At a certain point the degree of heating generated may cause damage to patient tissue. There may also be limits imposed by the properties of the electrodes used to deliver the electrical field therapy. Above a certain upper amplitude limit, delivered electrical field therapy may result in the degradation of the electrode, which may in turn result in a loss of performance and potentially the release of degradation products from the electrode which may result in biological harm to the patient tissue through toxicity, activation of inflammatory pathways and other means. Engineering constraints may also provide a secondary consideration in setting upper limits of amplitude due to the energy requirements (which may make it difficult to power systems with portable batteries) and hardware challenges in designing systems that operate across wide amplitude ranges. Amplitude may be either monophasic (direct current) or biphasic (alternating current). The desirable window of amplitude may vary according to the design of the system (number, location and orientation of electrodes), performance of the electrodes and the tumour profile. In one embodiment selecting, or determining, the regimen parameters comprises selecting, or determining, the amplitude wherein the amplitude is ± 0.1 - 500 mA (current) and/or ± 0.5 - 50V (voltage).

In one embodiment selecting, or determining, the regimen parameters comprises selecting, or determining, the amplitude of the current.

In one embodiment selecting, or determining, the regimen parameters comprises selecting, or determining, the amplitude of the current wherein the amplitude is ± 0.1 - 500 mA.

In one embodiment selecting, or determining, the regimen parameters comprises selecting, or determining, the amplitude of the current wherein the amplitude is ± 0.1 - 15 mA.

In one embodiment selecting, or determining, the regimen parameters comprises selecting, or determining, the amplitude of the voltage.

In one embodiment selecting, or determining, the regimen parameters comprises selecting, or determining, the amplitude of the voltage wherein the amplitude is ± 0.5 - 50V.

In one embodiment selecting, or determining, the regimen parameters comprises selecting, or determining, the amplitude of the voltage wherein the amplitude is ± 0.5 - 10V.

In one embodiment selecting, or determining, the regimen parameters comprises selecting, or determining, the current or voltage amplitude in order to achieve a peak or root mean square electric field strength.

In one embodiment selecting, or determining, the regimen parameters comprises selecting, or determining, the current or voltage amplitude in order to achieve a peak or root mean square electric field strength in the range of 0.5 - 25V/cm across the tumour.

In one embodiment selecting, or determining, the regimen parameters comprises selecting, or determining, the current or voltage amplitude in order to achieve a peak or root mean square electric field strength in the range of l-5V/cm across the tumour.

In one embodiment selecting, or determining, the regimen parameters comprises selecting, or determining, the direction of the current.

In one embodiment selecting, or determining, the regimen parameters comprises selecting, or determining, the direction of the current wherein a varying phase difference is applied to the regimens delivered at each electrode.

In one embodiment selecting, or determining, the regimen parameters comprises selecting, or determining, the duration of treatment. The profile of a tumour may change with respect to time. This could be caused by pathological processes associated with the disease or through the effect of therapy (whether the electrical field therapy or other therapy). For instance, a therapy may preferentially kill particular cells within the tumour population based on their genetics or other factors. Thereby, the proportion of that particular cell population within the tumour may decrease over time. This may impact the tumour profile and therefore the expected impact of a particular regimen against that tumour. It therefore follows that the optimal regimen for the treatment of a tumour may change with respect to time. If it is the electrical field therapy itself that is driving the change in tumour profile, it may be that the particular regimen utilised is preferentially killing particular cancer cells within the tumour population based on their genetic profile or other characteristics. In this way, the regimen is selecting for cancer cells that are more resistant to the therapeutic mechanisms of the therapy. Therefore, the therapeutic impact of the employed regimen would be expected to diminish with respect to time. At a later timepoint or timepoints in the treatment period, the tumour could be re-profiled and the treatment regimen parameters adjusted according to the changed profile of the tumour.

In order to counteract this effect, the delivered regimen could be cyclically altered with respect to time, whereby a particular set of parameters are used to target one population of cells and a second set of parameters are used to target a second population of cells. Multiple sets of parameters can be used sequentially to target different cell populations in this way. The regimen could consist of cycles of these sequential sets of these varying parameters. The length of time one set of parameters is delivered before progressing to the next stage of the sequence should be factored in - it should be a long enough period of time for the desired biological effect in the target cells to take place but it not be too long as this would extend the delay in which the non-optimal cancer cell populations are not being targeted, thereby allowing those cancer cell populations time to grow or recover from the effects of the previous cycle of treatment, ultimately reducing therapeutic benefit.

In one embodiment selecting, or determining, the regimen parameters comprises selecting, or determining, different regimen parameters for different regions of the tumour and cycling between them over time.

In one embodiment selecting, or determining, the regimen parameters comprises selecting, or determining, different regimen parameters for different cell populations in the tumour and cycling between them over time. Cell populations may be dispersed across the whole tumour or present within different distinct regions of the tumour.

Profile of the tumour

In one embodiment the profile of the tumour comprises the genetic and/or epigenetic and/or molecular and/or transcriptomic profile of the tumour.

Determining, i.e. obtaining, the profile of the tumour can be carried out using known techniques, for example either RNA and/or DNA sequencing and/or array technologies including but not limited to RNA and/or DNA and/or proteomic sequencing and /or arrays.

In one embodiment, determining the profile of the tumour may be achieved by RNA sequencing.

In one embodiment, determining the profile of the tumour may be achieved by DNA sequencing. In one embodiment determining the profile could be done using MRI and/or dTI MRI and/or Contrast enhancing MRI and/or PET imaging (https://www.sciencedirect.com/science/article/abs/pii/S0950705121007528).

In one embodiment determining the profile could be done using light microscope and/or advanced microscopy with fluorescent and/or chemiluminescent probes to characterize stainings.

In one embodiment determining the profile could be done using real time PCR and/or qPCR and/or digital PCR.

In one embodiment determining the profile could be done using protein expression using western blot and/or array blots and/or mass spectroscopy and/or proteomic arrays.

In one embodiment the profile of the tumour comprises the epigenetic profile of the tumour which may be achieved by methylation sequencing and/or long read DNA sequencing and/or RNA sequencing and/or bisulphite sequencing.

In one embodiment the profile of the tumour comprises the genetic profile of the tumour.

In one embodiment the profile of the tumour comprises the epigenetic profile of the tumour.

In one embodiment the profile of the tumour comprises the molecular profile of the tumour.

In one embodiment the profile of the tumour comprises the transcriptomic profile of the tumour.

In one embodiment where the tumour is glioblastoma, the profile of the tumour comprises the proneural, classical, and/or mesenchymal subtype profile.

In one embodiment where the tumour is glioblastoma, the profile of the tumour comprises the proneural, classical, and/or mesenchymal subtype profile of a region of the tumour.

In one embodiment where the tumour is glioblastoma, the profile of the tumour comprises the proneural, classical, and/or mesenchymal subtype profile of the margins of the tumour.

In one embodiment where the tumour is glioblastoma, the profile of the tumour comprises the proneural, classical, and/or mesenchymal subtype profile of populations of cells within the tumour.

In one embodiment the profile of the tumour comprises the profile of an excised tumour following surgical resection.

In one embodiment the profile of the tumour comprises the profile of a biopsy sample.

In one embodiment the profile of the tumour comprises the profile of tumour margins following surgical resection.

In one embodiment the profile of the tumour comprises the profile of the whole tumour.

In one embodiment the profile of the tumour comprises the profile of a specific region of the tumour.

In one embodiment the profile of the tumour comprises determining the profile of one or more cell populations in the tumour. In one embodiment the profile of the tumour comprises the profile of a specific region of the tumour margin following surgical resection.

Therapeutically effective amount

Therapeutically effective amount refers to an amount electric field therapy that is capable of producing a medically desirable result in a treated subject, i.e. treatment.

As used herein, the terms "treatment" and "treat" refer to reversing, alleviating, delaying the onset of, or inhibiting the progress of a disease or disorder, or one or more symptoms thereof, as described herein. In some embodiments, treatment may be conducted after one or more symptoms have developed. In other embodiments, treatment may be conducted in the absence of symptoms. For example, treatment may be conducted to a susceptible individual prior to the onset of symptoms (e.g. in light of a history of symptoms and/or in light of genetic or other susceptibility factors). Treatment may also be continued after symptoms have resolved, for example to present or delay their recurrence. In some embodiments treatment may refer to treatment following surgical resection.

Herein where use in the treatment of a tumour is described, this may refer to treatment of cancer in early stage, actively progressing, metastatic and/or drug-resistant cancer. In some embodiments where treatment or a tumour and/or cancer is referred to, the cancer is early cancer. In some embodiments where treatment or a tumour and/or cancer is referred to, the cancer is locally advanced cancer. In some embodiments where treatment or a tumour and/or cancer is referred to, the cancer is locally advanced and/or metastatic cancer. In some embodiments where treatment or a tumour and/or cancer is referred to, the cancer is metastatic cancer. In some embodiments where treatment or a tumour and/or cancer is referred to the cancer is invasive cancer.

In one embodiment the profile of the tumour may be re-determined after treatment and the regimen parameters adjusted for additional electric field therapy treatment.

Combination

In one embodiment the electric field therapy described herein, may be administered in combination with chemotherapy and /or radiotherapy.

In one embodiment the electric field therapy described herein, may be administered in combination with chemotherapy and radiotherapy.

In one embodiment the electric field therapy described herein, may be administered in combination with chemotherapy.

In one embodiment the electric field therapy described herein, may be administered in combination with temozolomide (TMZ).

In one embodiment the electric field therapy described herein, may be administered in combination with temozolomide (TMZ) and / or radiotherapy. In one embodiment the electric field therapy described herein, may be administered in combination with temozolomide (TMZ) and radiotherapy.

In one embodiment the electric field therapy described herein, may be administered in combination with radiotherapy.

In one embodiment the electric field therapy described herein, may be administered in combination with a PARP inhibitor (an inhibitor of the enzyme poly ADP ribose polymerase).

In one embodiment the electric field therapy described herein, may be administered in combination with a PARP inhibitor wherein the PARP inhibitor is selected from olaparib, rucaparib, niraparib, talazoparib, veliparib, or pamiparib.

In one embodiment the electric field therapy described herein, may be administered in combination with a PARP inhibitor and radiotherapy.

In one embodiment the electric field therapy described herein, may be administered in combination with a PARP inhibitor and radiotherapy wherein the PARP inhibitor is selected from olaparib, rucaparib, niraparib, talazoparib, veliparib, or pamiparib.

Herein, where the term "combination" is used it is to be understood that this refers to simultaneous, separate or sequential administration. In one aspect of the present disclosure, "combination" refers to simultaneous administration. In another aspect of the present disclosure, "combination" refers to separate administration. In a further aspect of the present disclosure, "combination" refers to sequential administration. Where the administration is sequential or separate, the delay in administering the second component should not be such as to lose the beneficial effect of the combination.

Process

The electric field therapy regimen described herein may be identified and deployed in practice as follows:

1. The patient's tumour is characterised for example through a molecular profile (through RNA sequencing or similar techniques) of a sample or samples of the tumour tissue acquired through biopsy or from explanted tumour tissue removed during resection surgery AND/OR the tumour is characterised non-invasively (through MRI or similar techniques).

2. Characterisation data is fed into a software algorithm run on a computer system that may physically located in the treatment centre or may be located remotely. The software algorithm analyses the tumour based on the profile, maps that against a known library of the response of different cell lines, and recommends treatment regimen parameters that are expected to be effective in the treatment of that tumour. The algorithm may be based on, for example, Qiagen's® Ingenuity Pathway Analysis software, or ALASCA (based in the Python language) developed by incubate. bio. 3. An electric field therapy device is then programmed / configured to deliver a therapeutic regimen with those parameters. The programming could be performed by the clinician, a third party or automatically. Programming signals could be sent to the electric field therapy device via wired or wireless connection or through physical controls (e.g. buttons). Suitable electric field therapy devices include implanted pulse generators (IPGs) for example those used in deep brain stimulation for the alleviation of Parkinson's Disease tremors.

In one embodiment there is provided a computer system comprising a processor configured to perform steps (i)-(iii) of the method for improving electric field therapy as described herein.

In one embodiment there is provided a computer system comprising a processor configured to perform steps (i)-(iv) of the method for improving electric field therapy as described herein.

In one embodiment there is provided a computer program comprising instructions which, when the program is executed by a computer, cause the computer to carry out steps (i)-(iii) of the method for improving electric field therapy as described herein.

In one embodiment there is provided a computer program comprising instructions which, when the program is executed by a computer, cause the computer to carry out steps (i)-(iv) of the method for improving electric field therapy as described herein.

In one embodiment there is provided a computer-readable storage medium comprising instructions which, when executed by a computer, cause the computer to carry out steps (i)-(iii) of the method for improving electric field therapy as described herein.

In one embodiment there is provided a computer-readable storage medium comprising instructions which, when executed by a computer, cause the computer to carry out steps (i)-(iv) of the method for improving electric field therapy as described herein.

In one embodiment there is provided a method for configuring an electric field therapy device configured with the regimen parameters determined by steps (i)-(iii) of the method for improving electric field therapy as described herein.

In one embodiment there is provided a method of programming an electric field therapy device for delivering an electric field therapy regimen to a patient with a tumor which comprises:

(ii) generating an analysis of the tumour from the received data;

(iv) configuring the electric field therapy device to deliver electric field therapy employing those parameters. Use

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is a solid tumour.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is a malignant solid tumour.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is:

• a brain tumour (including Grade I, 11, III or IV glioma; pilocytic astrocytoma; subependymal giant cell astrocytoma; diffuse astrocytoma; oligodendroglioma; oligodendroglioma NOS; anaplastic astrocytoma; anaplastic oligodendroglioma; anaplastic oligodendroglioma NOS; glioblastoma; giant-cell glioblastoma; glioblastoma; subependymal giant cell astrocytoma; pilomyxoid astrocytoma; pleomorphic xanthoastrocytoma; ganglioglioma; oligoastrocytoma; meningiomas (including grade I, II or III meningioma and other neoplasms related to the meninges (for example haemangiopericytoma)); paediatric brain tumours (including ependymoma, medulloblastoma, atypical teratoid/rhabdoid tumour (AT/RT); choroid plexus papilloma; choroid plexus carcinoma; intracranial teratoma; and embryonal tumours with multilayered rosettes (ETMR)), pineal region tumours (for example pineoblastoma), pituitary region tumours (for example pituitary adenoma, craniopharyngioma, and chordoma), brain metastases or diffuse midline glioma;

• pancreatic cancer (for example locally advanced pancreatic adenocarcinoma);

• ovarian cancer (for example ovarian cancer resistant to chemotherapy);

• liver cancer (for example advanced hepatocellular cancer);

• breast cancer;

• cervical cancer;

• colorectal carcinoma;

• gastric cancer (including gastric adenocarcinoma);

• malignant melanoma;

• renal adenocarcinoma; or

• urinary transitional cell carcinoma.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is a brain tumour. In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is a Grade I, 11, III or IV glioma.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is a Grade I glioma.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is pilocytic astrocytoma.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is a Grade II glioma.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is diffuse astrocytoma or oligodendroglioma.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is a Grade III glioma.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is anaplastic astrocytoma or anaplastic oligodendroglioma.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is a Grade IV glioma.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is diffuse midline glioma.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is brain metastases.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is giant-cell glioblastoma or glioblastoma.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is glioblastoma.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is recurrent glioblastoma.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is a brain tumour that has been surgically resected.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is a Grade I, 11, III or IV glioma that has been surgically resected.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is a Grade I glioma that has been surgically resected. In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is pilocytic astrocytoma that has been surgically resected.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is a Grade II glioma that has been surgically resected.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is diffuse astrocytoma or oligodendroglioma that has been surgically resected.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is a Grade III glioma that has been surgically resected.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is anaplastic astrocytoma or anaplastic oligodendroglioma that has been surgically resected.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is a Grade IV glioma that has been surgically resected.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is diffuse midline glioma that has been surgically resected.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is brain metastases that has been surgically resected.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is giant-cell glioblastoma or glioblastoma that has been surgically resected.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is glioblastoma that has been surgically resected.

In one embodiment there is provided electric field therapy as described herein for use in the treatment of a patient with a tumour wherein the tumour is recurrent glioblastoma that has been surgically resected.

In one embodiment there is provided electric field therapy as described herein for use in provoking ferroptosis and/or apoptosis. Method of treatment

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is a solid tumour.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is a malignant solid tumour.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is:

• pancreatic cancer (for example locally advanced pancreatic adenocarcinoma);

• ovarian cancer (for example ovarian cancer resistant to chemotherapy);

• liver cancer (for example advanced hepatocellular cancer);

• breast cancer;

• cervical cancer;

• colorectal carcinoma;

• gastric cancer (including gastric adenocarcinoma);

• malignant melanoma;

• renal adenocarcinoma; or • urinary transitional cell carcinoma.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is a brain tumour.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is a Grade I, II, III or IV glioma.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is a Grade I glioma.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is pilocytic astrocytoma.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is a Grade II glioma.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is diffuse astrocytoma or oligodendroglioma.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is a Grade III glioma.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is anaplastic astrocytoma or anaplastic oligodendroglioma.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is a Grade IV glioma.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is diffuse midline glioma.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is brain metastases. In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is giant-cell glioblastoma or glioblastoma.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is glioblastoma.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is recurrent glioblastoma.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is a brain tumour that has been surgically resected.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is a Grade I, II, III or IV glioma that has been surgically resected.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is a Grade I glioma that has been surgically resected.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is pilocytic astrocytoma that has been surgically resected.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is a Grade II glioma that has been surgically resected.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is diffuse astrocytoma or oligodendroglioma that has been surgically resected.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is a Grade III glioma that has been surgically resected.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is anaplastic astrocytoma or anaplastic oligodendroglioma that has been surgically resected. In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is a Grade IV glioma that has been surgically resected.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is diffuse midline glioma that has been surgically resected.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is brain metastases that has been surgically resected.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is giant-cell glioblastoma or glioblastoma that has been surgically resected.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is glioblastoma that has been surgically resected.

In one embodiment there is provided a method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein wherein the tumour is recurrent glioblastoma that has been surgically resected.

In one embodiment there is provided a method of provoking ferroptosis and/or apoptosis the method comprising administering to the patient a therapeutically effective electric field therapy regimen as described herein.

Kits

In one embodiment there is provided a kit comprising an electric field therapy device programmed to deliver an electric field therapy regimen as described herein.

In one embodiment there is provided a kit comprising an electric field therapy device programmed to deliver an electric field therapy regimen as described herein and one or more electrodes.

In one embodiment there is provided a kit comprising an electric field therapy device programmed to deliver an electric field therapy regimen as described herein and one or more implanted electrodes.

In one embodiment there is provided a kit comprising an electric field therapy device programmed to deliver an electric field therapy regimen as described herein and one or more external electrodes. BRIEF DESCRIPTION OF THE FIGURES

Figure 1 shows the results from Experiment 1 and the percent viable cells over control for different frequencies on different primary patient derived cell lines that conform to one of the three major subtypes of GBM (tested using Alamar Blue® viability stain). The data shows that there is a variability in viability not only between the different cell lines of different subtypes, but also within a subtype depending on the frequency used. This shows that the regimen may be tailored to target different subtypes more efficiently by using different frequencies.

Figure 2 shows the results from Experiment 2 and the top 30 differentially expressed canonical pathways between two different cell lines and between two different frequencies tested within them. White and black shadings represent higher and lower relative expression levels, respectively. The Ingenuity Pathway Analysis® tool from Qiagen® highlights the differences between the top 30 canonical pathways that are differentially regulated between the different EFT regimens and different cell lines. The differences highlight that there are frequency dependent changes occurring between and within the cell lines.

EXAMPLES

Experiment 1: Effect of different frequencies on different cell lines

Four well characterised patient derived glioma stem cell lines were obtained from Dr Rossella Galli, San Raffaele Scientific Institute and cultured in serum free media supplemented with growth factors as described before (doi: 10.1158/0008-5472.CAN-04-1364; doi: 10.1007/978-l-4939-9145-7_9; doi: 10.1038/s41374-020-0437-0; doi: 10.1038/s41418-018-0248-7). Cells from all cell lines were seeded at 1.5 x 10⁴ cells/well density in 24-well plates in triplicates. The 24-well plates were then placed into an in vitro stimulation system to mimic the human clinical application of this technology. The stimulation system subjected the samples to an electric field regimen with a charge-balanced biphasic sinusoidal voltage waveform that had a frequency ranging from 25kHz - 550kHz and resulted in an electrical field strength (E) ranging from 1 - 5V/cm across each well. Cells in media alone without stimulation were used as control. Cell viability was measured using a resazurin reduction assay (Alamar Blue®, Thermofisher Scientific, UK), which was performed according to manufacturer's instructions. The results are shown in Figure 1.

Experiment 2: Ingenuity pathway analysis

Two patient derived glioma stem cell lines (classical and classical+mesenchymal mix) from Experiment 1 were seeded at 2 x 10⁵ cells/well density in 6-well plates in triplicates. The 6-well plates were then placed into an in vitro stimulation system to mimic the human clinical application of this technology. The system delivered an EFT regimen to the cells consisting of a charge-balanced biphasic sinusoidal voltage waveform that had a frequency of either 115kHz or 450khz and resulted in an electrical field strength (E) ranging from 1 -5 V/cm across each well. Cells in media alone without stimulation were used as control. Cells were harvested at the end of the EFT regimen and total RNA was extracted using the QIAGEN® RNeasy® RNA isolation kit according to manufacturer's protocol. Gene expression analysis was performed by RNA-seq. RNA was sequenced by Azenta Lifesciences® using an Illumina® Novoseq® machine as per manufacturer's protocol. Raw data were analysed using DESeq2 software. Differential gene expression analysis was calculated using the reads per kilobase million (RPKM) values of EFT treated samples vs its corresponding media control. An adjusted p-value of 0.05 was set as a cutoff and enriched pathways were determined using the Ingenuity Pathway Analysis® from Qiagen®. Comparisons were run across all conditions and the top 30 differentially expressed canonical pathway was extracted. The results are shown in Figure 2.

Statements

Statement 1. An electric field therapy regimen for administering to a patient with a tumour, wherein the regimen parameters are selected for the profile of the tumour.

Statement 2. An electric field therapy regimen as stated in statement 1 wherein the profile of the tumour comprises the profile of the whole tumour.

Statement 3. An electric field therapy regimen as stated in any one of the preceding statements wherein the profile of the tumour comprises the profile of one or more regions of the tumour. Statement 4. An electric field therapy regimen as stated in any one of the preceding statements wherein the profile of the tumour comprises the profile of one or more cell populations within the tumour.

Statement 5. An electric field therapy regimen as stated in any one of the preceding statements wherein the profile of the tumour comprises the genetic profile of the tumour.

Statement 6. An electric field therapy regimen as stated in any one of the preceding statements wherein the profile of the tumour comprises the epigenetic profile of the tumour.

Statement 7. An electric field therapy regimen as stated in any one of the preceding statements wherein the profile of the tumour comprises the molecular profile of the tumour.

Statement 8. An electric field therapy regimen as stated in any one of the preceding statements wherein the profile of the tumour comprises the transcriptomic profile of the tumour.

Statement 9. An electric field therapy regimen as stated in any one of the preceding statements wherein the profile of the tumour is determined by RNA sequencing.

Statement 10. An electric field therapy regimen as stated in any one of the preceding statements wherein selecting the regimen parameters comprises selecting the frequency.

Statement 11. An electric field therapy regimen as stated in any one of the preceding statements wherein selecting the regimen parameters comprises selecting the amplitude of the current. Statement 12. An electric field therapy regimen as stated in any one of the preceding statements wherein selecting the regimen parameters comprises selecting the amplitude of the voltage.

Statement 13. An electric field therapy regimen as stated in any one of the preceding statements wherein selecting the regimen parameters comprises selecting the electric field strength.

Statement 14. An electric field therapy regimen as stated in any one of the preceding statements wherein selecting the regimen parameters comprises selecting the direction of the current.

Statement 15. An electric field therapy regimen as stated in any one of the preceding statements wherein selecting the regimen parameters comprises selecting the duration of treatment.

Statement 16. An electric field therapy regimen as stated in any one of the preceding statements wherein the tumour is glioblastoma.

Statement 17. An electric field therapy regimen as stated in statement 16 wherein the profile comprises the proneural, classical, and/or mesenchymal subtype profile.

Statement 18. An electric field therapy regimen as stated in any one of the preceding statements wherein selecting the regimen parameters comprises selecting different regimen parameters for different regions of the tumour and/or different cell populations in the tumour and cycling between them over time.

Statement 19. A method of electric field therapy which comprises an electric field therapy regimen as stated in any one of statements 1-18.

Statement 20. A method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy regimen as stated in any one of statements 1-18.

Statement 21. Electric field therapy for use in the treatment of a patient with a tumour wherein the electric field therapy comprises administering to the patient a therapeutically effective electric field therapy regimen as stated in any one of statements 1-18.

Statement 22. The method or use as stated in statements 19-21 further comprising determining the profile of the tumour.

Statement 23. The method or use as stated in statements 19-22 further comprising determining the profile of the tumour after treatment and adjusting the regimen parameters for additional treatment. Statement 24. The method or use as stated in statements 19-23 wherein the regimen is administered in combination with chemotherapy and /or radiotherapy.

Statement 25. The method or use as stated in statements 19-24 wherein the electric field therapy comprises multiple electrodes implanted into the tumour or, following surgical resection, the tumour resection margin.

Statement 26. The method or use as stated in statements 19-25 wherein the electric field therapy comprises a biphasic injectable electrode which comprises a plurality of solid particles and a transporter phase, wherein both the solid particles and the transporter phase comprise poly(3,4- ethylenedioxythiophene)polystyrene sulfonate, injected into a tumour cavity following surgical resection.

Statement 27. An electric field therapy device programmed to deliver an electric field therapy regimen as stated in any one of statements 1-18.

Claims

P-000050-WO-PCT-QVB Claims What is claimed is:

1. A method for improving electric field therapy for delivering to a patient with a tumor which comprises:

(ii) generating an analysis of the tumour from the received data;

2. A method as claimed in claim 1 wherein the profile of the tumour comprises the profile of the whole tumour.

3. A method as claimed in any one of the preceding claims wherein the profile of the tumour comprises the profile of one or more regions of the tumour.

4. A method as claimed in any one of the preceding claims wherein the profile of the tumour comprises the profile of one or more cell populations within the tumour.

5. A method as claimed in any one of the preceding claims wherein the profile of the tumour comprises the genetic profile of the tumour.

6. A method as claimed in any one of the preceding claims wherein the profile of the tumour comprises the epigenetic profile of the tumour.

7. A method as claimed in any one of the preceding claims wherein the profile of the tumour comprises the molecular profile of the tumour.

8. A method as claimed in any one of the preceding claims wherein the profile of the tumour comprises the transcriptomic profile of the tumour. P-000050-WO-PCT-QVB

9. A method as claimed in any one of the preceding claims wherein the profile of the tumour is obtained by RNA sequencing.

10. A method as claimed in any one of the preceding claims wherein the regimen parameters comprise the frequency of the electric field therapy regimen.

11. A method as claimed in any one of the preceding claims wherein the regimen parameters comprise the amplitude of the current of the electric field therapy regimen.

12. A method as claimed in any one of the preceding claims wherein the regimen parameters comprise the amplitude of the voltage of the electric field therapy regimen.

13. A method as claimed in any one of the preceding claims wherein the regimen parameters comprise the electric field strength of the electric field therapy regimen.

14. A method as claimed in any one of the preceding claims wherein the regimen parameters comprise the direction of the current of the electric field therapy regimen.

15. A method as claimed in any one of the preceding claims wherein the regimen parameters comprise the duration of treatment of the electric field therapy regimen.

16. A method as claimed in any one of the preceding claims wherein the tumour is glioblastoma.

17. A method as claimed in claim 16 wherein the profile comprises the proneural, classical, and/or mesenchymal subtype profile.

18. A method as claimed in any one of the preceding claims wherein the electric field therapy comprises multiple electrodes.

19. A method as claimed in any one of the preceding claims wherein the electric field therapy comprises multiple electrodes implanted into the tumour or, following surgical resection, the tumour resection margin. P-000050-WO-PCT-QVB

20. A method as claimed in any one of the preceding claims wherein the electric field therapy comprises a biphasic injectable electrode which comprises a plurality of solid particles and a transporter phase, wherein both the solid particles and the transporter phase comprise poly(3,4- ethylenedioxythiophene)polystyrene sulfonate, injected into a tumour cavity following surgical resection.

21. A method of treating a patient with a tumour, the method comprising administering to the patient a therapeutically effective electric field therapy comprising an electric field therapy device configured according to step (iv) of the method any one of claims 1-20..

22. Electric field therapy for use in the treatment of a patient with a tumour wherein the electric field therapy comprises administering to the patient a therapeutically effective electric field therapy regimen comprising an electric field therapy device configured according to step (iv) of the method any one of claims 1-20..

23. An electric field therapy device configured to deliver the electric field therapy treatment regimen generated by steps (i)-(iii) of the method any one of claims 1-20.

24. A computer system comprising a processor configured to perform steps (i)-(iii) of the method of any one of claims 1-20.