Modulation of vascular adaptation within a tumor to increase therapy uptake within the tumor

1 . A method of delivering a dose of a therapy to an organ of a patient, comprising:

a) providing a pressure directed therapy system for delivering the therapy to a target artery feeding the organ of the patient, the system comprising,

i) a flexible tubular member having a proximal end and a distal end, an infusion lumen extending between the proximal and distal ends, the infusion lumen having a distal orifice at the distal end, wherein the flexible tubular member is configured to infuse the therapy into the target artery through the distal orifice;

ii) a deployable occluder mounted at the distal end of the tubular member, the occluder having a radially-collapsed, non-deployed configuration and a radially-expanded, deployed configuration; and

iii) a pressure sensor configured to sense fluid pressure in the target artery distal of the occluder;

b) advancing the occluder in the non-deployed configuration to the target artery of the organ;

c) sensing a first pressure in the target artery with the pressure sensor;

d) deploying the occluder into the deployed configuration within the target artery;

e) then infusing the therapy through the infusion lumen and out of the distal orifice at an infusion pressure higher than the first pressure,

f) tracking a running peak infusion pressure;

g) upon sensing, with the pressure sensor, a predetermined decrease in the infusion pressure relative to the running peak pressure, stopping infusion;

h) waiting for the pressure in the target artery to return to within ±10% of the first pressure; and

i) repeating steps e) through h) until the dose of the therapy has been delivered to the patient.

2 . The method of claim 1 , wherein the occluder of the system is a manually actuatable microvalve.

3 . The method of claim 1 , wherein the occluder of the system is an inflatable balloon.

4 . The method of claim 1 , wherein the infusing the therapy is at a constant rate.

5 . The method of claim 1 , wherein the sensing of the first pressure includes,

sensing a baseline pressure in the target artery when the occluder is in the non-deployed configuration; and

sensing a stabilized pressure in the target artery when the occluder is in the deployed configuration.

6 . The method of claim 1 , wherein deploying the occluder within the target artery at least partially reduces the fluid pressure within the target artery distal of the occluder.

7 . The method of claim 1 , wherein the predetermined decrease in infusion pressure is a decrease of at least 10% in the infusion pressure.

8 . A method of delivering a dose of a therapy to an organ of a patient, comprising:

a) providing a pressure directed therapy system for delivering the therapy to a target artery feeding the organ of the patient, the system comprising,

i) a flexible tubular member having a proximal end and a distal end, an infusion lumen extending between the proximal and distal ends, the infusion lumen having a distal orifice at the distal end, wherein the flexible tubular member is configured to infuse the therapy into the target artery through the distal orifice;

ii) an expandable occluder mounted at the distal end of the tubular member; and

iii) a pressure sensor to sense fluid pressure in the target artery distal of the occluder;

b) advancing the occluder of the system to the target artery of the organ;

c) sensing a first pressure in the target artery with the pressure sensor;

d) deploying the occluder within the target artery to at least partially reduce the fluid pressure within the target artery distal of the occluder;

e) sensing, with the pressure sensor, a stabilized pressure in the target artery after deploying the occluder;

f) then infusing the therapy through the infusion lumen and out of the distal orifice at a constant rate and a variable infusion pressure higher than the stabilized pressure, the variable infusion pressure having a peak pressure sensed by the pressure sensor;

g) upon sensing, with the pressure sensor, a decrease in the variable infusion pressure from the peak pressure by at least 3%, stopping the infusing;

h) waiting for the stabilized pressure in the target artery to return to a lower pressure determined for re-infusion; and

i) repeating steps f) through h) until the dose of the therapy has been delivered to the patient.

9 . The method of claim 8 , wherein infusing is stopped when the decrease in variable infusion pressure from the peak pressure is by at least 5%.

10 . The method of claim 8 , wherein at least one of the stabilized pressure, the variable infusion pressure, the peak pressure, and the lower pressure is an average lower pressure over time.

11 . The method of claim 8 , wherein the stabilized pressure in the target artery is an average stabilized pressure over time, the variable infusion pressure is an average running variable infusion pressure over time, the peak pressure is an average peak pressure over time, and the lower pressure is an average lower pressure over time.

12 . A method of delivering a dose of a therapy through a target artery to a solid tissue of a patient, comprising:

a) providing a pressure directed therapy system for delivering the therapy to the target artery feeding the solid tissue of the patient, the system having,

i) a flexible tubular member having a proximal end and a distal end, an infusion lumen extending between the proximal and distal ends, the infusion lumen having a distal orifice at the distal end, wherein the flexible tubular member is configured to infuse the therapy into the target artery through the distal orifice;

ii) an expandable occluder mounted at the distal end of the tubular member, the occluder having a reduced diameter first configuration for advancement through the target artery and an expanded second configuration for occluding flow of blood within the target artery, the occluder having an impermeable coating on a portion thereof that prevents passage of blood through the impermeable coating; and

iii) a pressure sensor to sense fluid pressure in the target artery distal of the occluder;

b) advancing a portion of the pressure directed therapy system into the target artery while the occluder is in the first configuration;

c) using the pressure sensor to determine a baseline pressure in the target artery; then,

d) expanding the occluder into the second configuration to effect reduction of the pressure in the target artery by at least 20 percent below the baseline pressure to a second pressure, wherein the second pressure primes the target artery for uptake of the therapy; and then,

e) infusing the therapy into the target artery at an infusion pressure exceeding the baseline pressure.

13 . The method of claim 12 , wherein:

the pressure in the target artery is reduced by at least 40 percent below the baseline pressure prior to infusing the therapy.

14 . The method of claim 12 , wherein:

the pressure in the target artery is reduced by at least 50 percent below the baseline pressure prior to infusing the therapy.

15 . A method of delivering a dose of a therapy through a target artery to a solid tissue of a patient, comprising:

a) providing a pressure directed therapy system for delivering the therapy to the target artery feeding the solid tissue of the patient, the system comprising,

i) a flexible tubular member having a proximal end and a distal end, an infusion lumen extending between the proximal and distal ends, the infusion lumen having a distal orifice at the distal end, wherein the flexible tubular member is configured to infuse the therapy into the target artery through the distal orifice;

ii) an expandable occluder mounted at the distal end of the tubular member, the occluder having a reduced diameter first configuration for advancement through the target artery and an expanded second configuration for occluding flow of blood within the target artery, the occluder having an impermeable coating on a portion thereof that prevents passage of blood through the impermeable coating; and

iii) a pressure sensor to sense fluid pressure in the target artery distal of the occluder;

b) advancing a portion of the pressure directed therapy system into the target artery while the occluder is in the first configuration;

c) using the pressure sensor to determine a baseline pressure in the target artery; then,

d) expanding the occluder into the second configuration to effect reduction of the pressure in the target artery below the baseline pressure to a second pressure, wherein the second pressure primes the target artery for uptake of the therapy; and then,

e) infusing the therapy into the target artery at an infusion pressure exceeding the baseline pressure;

f) tracking a running peak infusion pressure;

g) upon sensing, with the pressure sensor, a predetermined decrease in the infusion pressure relative to the tracked running peak infusion pressure, stopping infusion;

h) waiting for the pressure in the target artery to return to the within ±10% of the baseline pressure; and then

i) repeating steps f) through h) until the dose of the therapy has been delivered to the patient.