NanoTherm® Therapy System (NTTS)

The treatment with the NanoTherm® Therapy System (NTTS) is based on superparamagnetic iron oxide nanoparticles that are applied locally to the tumor (recurrent glioblastoma). Inside the tissue, they convert the energy of the alternating magnetic field of the NanoActivator® into heat. This heat is released into the adjacent (tumor) tissue leading to local destruction or damage of the tumor cells (thermal ablation, T ≥ 46°C) or to a higher susceptibility to concomitant chemotherapy or radiotherapy (hyperthermia, T ≤ 46°C) which depends on the local temperatures reached. The recommended thermotherapy schedule includes six one-hour treatments (minimum interval of 48 hours) in the NanoActivator® over a period of three weeks. The first activation should take place after sufficient wound healing and at least 3 days after neurosurgery.

Hyperthermia and thermal ablation

Therapy with NTTS leads to heat in tissue. Depending on the local temperatures, the heat kills the recurrent glioblastoma tumor cells (thermal ablation) or makes them more susceptible for concurrent radiotherapy or chemotherapy (hyperthermia).

Clinical benefit of the treatment with the NanoTherm® Therapy System is as follows:

In addition to the significantly well tolerated and localized treatment, the main clinical benefit that must be mentioned is the increase in the probability of a potential extension of the expected overall survival time for the patient. This likelihood of increased survival for individuals continues to depend on the tumor and subjective characteristics of the patient, including genetic and hereditary factors, as well as age and Karnofsky Performance Status.

 

Products

The NanoTherm® Therapy System (NTTS) consists of the following medical devices:

  • NanoTherm® AS1
  • NanoActivator®
  • NanoPlan®
  • Thermometry
  • Hyperthermia Catheter 3F

The precise description of functionality and mode of operation of the medical devices can be found in the relevant instructions for use supplied with these products.

NanoTherm® AS1

NanoTherm® AS1 is used for local thermotherapy of recurrent glioblastomas. NanoTherm® AS1 is applied to the treatment area and remains in the patient after treatment. The administration of NanoTherm® AS1 and the implementation of the therapy is subject to the discretion of the treating physician. NanoTherm® AS1 is intended to be applied exclusively by a neurosurgeon who is trained in this field. The subsequent activations of the NanoTherm® AS1 nanoparticles in the NanoActivator® can be performed by medical technicians trained in this procedure. NanoTherm® AS1 is intended for single use and must not be reprocessed.

NanoActivator®

The NanoActivator® is designed only for the thermotherapy of biological tissue in combination with the active implantable medical device NanoTherm® AS1. For this purpose, the NanoActivator® generates a homogeneous alternating magnetic field that is intended to activate the previously implanted NanoTherm® AS1 nanoparticles. Thus, locally heating the brain cancer tissue (recurrent glioblastoma) in the target area to hyperthermia and/or thermal ablation temperatures).

NanoPlan®

NanoPlan® as medical device software (accessory to the NanoActivator®) is used for postoperative simulation of the temperature distribution in the treatment area and for the purpose of providing the corresponding magnetic field strength. The simulation is based on CT imaging data of the treatment area with implanted NanoTherm® AS1.

Thermometry

Thermometry as an accessory to the NanoActivator® is intended to determine, display, and record the treatment temperature in the brain tumor (recurrent glioblastoma) during the (at least initial) treatment with the NanoActivator®.

The calibration trolley as an accessory to the thermometry is used to provide reference temperature values for the purpose of calibration or offset adjustment of the temperature sensors.

Hyperthermia Catheter 3F

The closed end Hyperthermia Catheter 3F as an accessory to the Thermometry is inserted into the treatment area during application procedure of NanoTherm® AS1 and is used as a sterile sheath and guide for the (unsterile) fiber-optical temperature sensor (probe) of the Thermometry. The probe is inserted directly prior to the first treatment session into a Hyperthermia Catheter 3F.

Indications and target populations

Recurrent Glioblastoma multiforme.

Contraindications

The following contraindications apply for the treatment with NTTS:

Electronic or metallic implants

Electronic or metallic implants can heat up during treatment in the NanoActivator® leading to a stop of functioning or causing burn injuries. Patients with such implants must not be treated unless the implant(s) can be removed or are located at more than 40 cm away from the rim of the alternating magnetic field. For this reason, patients with a cardiac pacemaker, an implanted defibrillator, or neurostimulation electrodes must not be treated in the NanoActivator® and are excluded from therapy with the NanoTherm® Therapy System. Metallic dental restorations must be removed before treating brain tumors.

Hypersensitivity

NanoTherm® AS1 is contraindicated in patients with hypersensitivity to:

  • iron oxide
  • amino silanes
  • acetic acid

Pregnancy and breastfeeding

Animal studies have shown no toxicity or teratogenicity with consequences for pregnancy or embryonic development. However, the medical device must not be used in these patients due to the lack of clinical experience with the use of NanoTherm® AS1 in pregnant and breast-feeding women.

Children and adolescents

There is no clinical experience for the use of NanoTherm® Therapy System in patients under 18 years old. The use of NanoTherm® Therapy System is therefore not recommended in these patients.

Body height and weight

Treatment with the NTTS is contraindicated for:

  • Patients taller than 190 cm
  • Patients heavier than 120 kg

Multifocality

Treatment for patients with more than 3 lesions is contraindicated, because every lesion is exposed to the same magnetic field, requiring individual temperature measurements at the same time. However, volume and concentration of the NanoTherm deposits can be different and thus compromise on the magnetic field strength to be applied in terms of the intratumoural temperature.