Method and device for treating microscopic residual tumors remaining in tissues following surgical resection
This invention concerns treating apparently normal tissue surrounding sites of cancerous tumors so as to reduce both the probability of a recurrence of cancer at and near the site of a cancerous tissue, and to reduce the amount of apparently healthy tissue that is usually excised along with the tumor, thereby providing a substantial benefit to the cancer patient by eliminating or delaying tumor recurrence and sparing normal tissue for its functionality and for avoiding unnecessary disfigurement.
1. A method of reducing recurrence of tumor cell growth in a mammalian tissue, the method comprising:
(a) providing a source for applying an electroporative electric pulse to an unexcised tumor mass and a margin tissue around the unexcised tumor mass;
(b) providing an agent capable of reducing tumor cell growth;
(c) injecting the agent into the unexcised tumor mass and the margin tissue around the unexcised tumor mass; and
(d) applying the electroporative electric pulse by the source to the unexcised tumor mass and the margin tissue around the unexcised tumor mass, thereby delivering the agent into cells of the unexcised tumor mass and the margin tissue around the unexcised tumor mass;
wherein recurrence of tumor cell growth in the mammalian tissue is reduced.
2. The method of claim 1 , wherein the agent is selected from the group consisting of Bleomycin, cisplatin, a polypeptide, an antibody, an RNAi, an antisense nucleic acid, an expressible gene encoding a therapeutically active polypeptide, a chemokine, and a cytokine.
3. The method of claim 2 , wherein the RNAi, the antisense nucleic acid, or the expressible gene is formulated in poly-L-glutamate solution.
4. The method of claim 1 , wherein the tumor cell is selected from the group consisting of: a cancer cell in cutaneous tissue, a cancer cell located on the head or neck of a mammal, a squamous cell carcinoma, a colon carcinoma, and a melanoma cell.
5. The method of claim 1 , wherein the electroporative electric pulse comprises a pulse having a nominal field strength selected from the group consisting of: between 800 and 1500 V/cm, between 600 and 1500 V/cm, between 600 and 1400 V/cm, between 200 and 800 V/cm, between 1 and 600 V/cm, between 200 to 600 V/cm, between 400 and 600 V/cm, 1200 V/cm, and 1500 V/cm.
6. The method of claim 1 , wherein the source comprises: an array of a multiplicity of electrodes capable of channeling a fluid volume from at least one variable volume reservoir to the unexcised tumor mass and the margin tissue around the unexcised tumor mass when the multiplicity of electrodes are positioned in the unexcised tumor mass and the margin tissue around the unexcised tumor mass, wherein said multiplicity of electrodes can be further energized in a predetermined format selected from the group consisting of energizing single pairs of electrodes, energizing opposed pairs of electrodes, energizing a selected portion of said electrodes sequentially, and energizing a selected portion of said electrodes simultaneously.
7. The method of claim 1 , wherein the source comprises:
(a) an array of a multiplicity of electrodes comprising lumens running therethrough for transporting a fluid medium;
(b) an array of compartments capable of containing a fluid medium and in fluid communication with said lumens;
(c) an array of plungers corresponding to said array of compartments wherein a plunger is fit into each compartment of said array of compartments and wherein said array of plungers are capable of slidably adjustable positioning in their respective compartments;
(d) an actuator for slidably adjusting positioning of said plungers; and
(e) a source of electrical energy connectable to said multiplicity of electrodes for imparting to said multiplicity of electrodes the electroporative electric pulse.
8. The method of claim 7 , wherein the actuator is a thumb wheel.
9. The method of claim 7 , wherein the actuator is a wing nut.
10. The method of claim 7 , wherein the actuator is an electric motor.
11. The method of claim 7 , wherein the actuator is screw driven.
12. The method of claim 1 , wherein the unexcised tumor mass has been liquified after step (d).
13. The method of claim 12 , wherein the unexcised tumor mass has undergone liquefactive necrosis after step (d).
14. The method of claim 13 , wherein the unexcised tumor mass has been debulked after step (d).
15. The method of claim 1 , wherein the unexcised tumor mass has been softened after step (d).
16. The method of claim 15 , wherein the unexcised tumor mass is softened within about 24 hours.
17. The method of claim 16 , wherein the unexcised tumor mass is softened within about 15 minutes.
18. The method of claim 1 , further comprising administering one or more additional cancer therapies.
19. The method of claim 18 , wherein the one or more additional cancer therapies is selected from the group consisting of: radiation, chemotherapy, and antibody therapy.
20. The method of claim 1 , wherein (d) further comprises treating microtumor seeding in the margin tissue.