title: Towards treatment planning and treatment of deep-seated solid tumors by electrochemotherapy.
abstract: BACKGROUND
  Electrochemotherapy treats tumors by combining specific chemotherapeutic drugs with an intracellular target and electric pulses, which increases drug uptake into the tumor cells. Electrochemotherapy has been successfully used for treatment of easily accessible superficial tumor nodules. In this paper, we present the first case of deep-seated tumor electrochemotherapy based on numerical treatment planning.
  
  
  METHODS
  The aim of our study was to treat a melanoma metastasis in the thigh of a patient. Treatment planning for electrode positioning and electrical pulse parameters was performed for two different electrode configurations: one with four and another with five long needle electrodes. During the procedure, the four electrode treatment plan was adopted and the patient was treated accordingly by electrochemotherapy with bleomycin. The response to treatment was clinically and radiographically evaluated. Due to a partial response of the treated tumor, the metastasis was surgically removed after 2 months and pathological analysis was performed.
  
  
  RESULTS
  A partial response of the tumor to electrochemotherapy was obtained. Histologically, the metastasis showed partial necrosis due to electrochemotherapy, estimated to represent 40-50% of the tumor. Based on the data obtained, we re-evaluated the electrical treatment parameters in order to correlate the treatment plan with the clinical response. Electrode positions in the numerical model were updated according to the actual positions during treatment. We compared the maximum value of the measured electric current with the current predicted by the model and good agreement was obtained. Finally, tumor coverage with an electric field above the reversible threshold was recalculated and determined to be approximately 94%. Therefore, according to the calculations, a small volume of tumor cells remained viable after electrochemotherapy, and these were sufficient for tumor regrowth.
  
  
  CONCLUSIONS
  In this, the first reported clinical case, deep-seated melanoma metastasis in the thigh of the patient was treated by electrochemotherapy, according to a treatment plan obtained by numerical modeling and optimization. Although only a partial response was obtained, the presented work demonstrates that treatment of deep-seated tumor nodules by electrochemotherapy is feasible and sets the ground for numerical treatment planning-based electrochemotherapy.
  
  
  BACKGROUND
  EudraCT:2008-008290-54.
authors.affiliation: Institute of Oncology Ljubljana, Zaloska 2, SI-1000 Ljubljana, Slovenia.
authors.forename: Damijan
authors.initials: D
authors.lastname: Miklavcic
authors.forename: Marko
authors.initials: M
authors.lastname: Snoj
authors.forename: Anze
authors.initials: A
authors.lastname: Zupanic
authors.forename: Bor
authors.initials: B
authors.lastname: Kos
authors.forename: Maja
authors.initials: M
authors.lastname: Cemazar
authors.forename: Mateja
authors.initials: M
authors.lastname: Kropivnik
authors.forename: Matej
authors.initials: M
authors.lastname: Bracko
authors.forename: Tjasa
authors.initials: T
authors.lastname: Pecnik
authors.forename: Eldar
authors.initials: E
authors.lastname: Gadzijev
authors.forename: Gregor
authors.initials: G
authors.lastname: Sersa
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D003198:Computer Simulation; D004599:Electric Stimulation Therapy / Q000379:methods*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000628:therapy*; D008875:Middle Aged; D008954:Models, Biological; D012878:Skin Neoplasms / Q000628:therapy*; D013813:Therapy, Computer-Assisted / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents