Patent Application
20170086899
The inventions described below relate to the field of cryosurgery and the treatment of breast cancer.
The methods described below provide for optimal treatment of invasive breast carcinoma. In our prior patents, we disclosed methods and systems for treating fibroadenomas in the breast of female patients. Our experience with fibroadenoma patients has led to the development of the new procedure described below which applies cryoablation therapy as a nonoperative approach to the treatment of primary breast tumors. The new procedure is simple, readily available for use with existing cryotherapy devices and is less painless to the patient for treatment of cancer.
The methods and systems described below provide for effective cryoablation of target cancerous lesions and a margin of tissue analogous to the surgical margins of a lumpectomy. Cryoablation is performed with a treatment regimen including two freeze cycles with an intervening passive warming period, without an intervening low-power freeze cycle. When accomplished with commercially available cryoprobes such as our Visica® argon gas cryoprobes system or our Visica II™ liquid nitrogen cryoprobes system, the method entails a period of freezing, followed by a period of passive warming, followed by a repetition of these steps, and optionally followed by a warming cycle to speed removal of the cryoprobe from the iceball.
To achieve the coincident iceball, the cryoprobes are adapted to achieve an iceball, which roughly matches the typical shape of a target lesion. The cryoprobe tip is pushed into and through the target lesion so that its distal tip protrudes from the far boundary of the target lesion. The cryoprobe is then operated to create an iceball operated for a period of time, which depends on the size of the lesion, necessary to create an iceball engulfing the lesion. The treatment is achieved with two freezing periods and with a passive warming/thawing period between the two freezing periods that is determined empirically to achieve warming sufficient to exhaust known warming cell-death mechanisms. Measurements are obtained after each freezing period to ensure that sufficient margins have been achieved. In clinical practice, it depends on the length of time a cryoprobe is operated and its duty cycle, and this in turn depends on the cooling power of the cryoprobes, the shape of the iceball, and the location of the cryoprobe tip relative to the lesion.
The cryoprobe used for the procedure may be our Visica 2™ 3.4 mm cryoprobe (which uses liquid nitrogen), our Visica® cryoprobe (which uses argon gas and a Joule-Thomson cryostat), or other commercially available cryoprobes. Our Visica 2™ cryoprobe and system are described in detail in our prior U.S. Pat. No. 7,976,538, issued Jul. 12, 2011 and application Ser. No. 11/318,142 filed Dec. 23, 2005 and Ser. No. 11/406,547 filed Apr. 18, 2006 (212/846) and their corresponding PCT application PCT/US06/48863 filed Dec. 22, 2006, the entirety of each being incorporated by reference. The treatment system uses a closed system to circulate liquid nitrogen within the probe tip creating sub-freezing temperatures that result in precision cryoablation of the intended tissue target. The target lesion is first appropriately identified and then the probe is placed under ultrasound guidance into the enter of the lesion and cryoablated according to a predetermined freeze algorithm consisting of a freeze cycle followed by a thaw cycle, followed by a final freeze cycle. The probe is then warmed by an internal electrical resistance heater and removed from the patient.
This method of treating cancerous legions described below provides for fast treatment without loss of effectiveness. Once situated and positioned properly relative to the target lesion, the cryoprobe is operated for two cycles of high-power freezing, with a passive warming period interposed between the cycles and a warming period provided after the second freezing cycle, without any intervening low-power freezing periods. The periods of high-power freezing are selected depending on the size of the lesion and expected time for the cryoprobe to grow an iceball with a −20° C. isotherm. The period of passive warming between freezing periods are limited to the period necessary to allow substantial completion of known cell-death mechanisms which occur during warming. With experimentation, we have empirically determined the following freeze periods for lesions of various sizes using the liquid nitrogen cryoprobes of our Visica 2™ system:
As indicated in the table, a lesion with a major axis smaller than 1 cm is treated with two freezing cycles consisting each of 6 minutes of freezing (engulfing the mass in a −20° C. isotherm), with 10 minutes of passive warming between the freezing cycles. A lesion with a major axis of 1 to 1.5 cm diameter is treated by two cycles of freezing, each consisting of 8 minutes of freezing, with 10 minutes of passive warming between the cycles. It is necessary to ensure that the iceball diameter exceeds the calculated maximum lesion width dimension by 10 mm on all sides via ultrasound after each freezing cycle. It the 10 mm margins are not met, the freeze time is exceeded to ensure the iceball diameter exceeds the 10 mm requirement.
Thus, the method entails operating the cryoprobe for a first cooling period to create an iceball having a −20° C. isotherm defining a volume engulfing the lesion, such that the −20° C. isotherm is substantially coincident with an outer margin of the lesion along an axis of the lesion (preferably matching the minor axis of the iceball to the minor axis of the lesion) and thereafter, without substantial delay, ceasing operation of the cryoprobe for a warming period limited to the time necessary to allow the iceball to warm to 0° C. (without thawing) and allow completion of warming cell death mechanism, and thereafter, again without substantial delay, operating the cryoprobe for a second cooling period to create an iceball having a −20° C. isotherm defining a volume engulfing the lesion such that the −20° C. isotherm is substantially coincident with an outer margin of the lesion along an axis of the lesion, and thereafter, again without substantial delay, ceasing cooling operation of the cryoprobe and allowing or causing the cryoprobe to warm as necessary to remove the cryoprobe. Also, the warming necessary to remove the cryoprobe may be augmented by application of heat through the cryoprobe through any suitable active warming mechanism.
The cooling periods are preferably predetermined, in the sense that they are determined empirically based on the typical time required to create an iceball having a −20° C. isotherm defining a volume engulfing a typical lesion of the same approximate size as the lesion to be treated with a cryoprobe of similar design to the cryoprobe used to treat the lesion. The second cooling period may be determined empirically, based on the typical time required to create an iceball having a −20° C. isotherm defining a volume engulfing a typical lesion of the same approximate size as the lesion to be treated (in which case it is equivalent to the first cooling period), or based on the typical time required to cool the warmed iceball to re-create an iceball having a −20° C. isotherm (in which case it may be substantially shorter than the first cooling period, because it starts from a frozen state). In use, achievement of the appropriate size iceball is confirmed between freezing periods by ultrasound. Specifically, after the first freezing period, the iceball length and width are determined to ensure that the iceball diameter exceeds the calculated maximum lesion width dimension by 10 mm on all sides as determined by the ultrasound. If the 10 mm benchmark is not achieved, the first freezing time is extended. At the end of the second freezing period, the iceball length and width are measured again to ensure that iceball diameter exceeds the calculated maximum lesion width dimension by 10 mm on all sides as determined by the ultrasound. If the 10 mm benchmark is not achieved, the second freezing time is extended. Because cryoprobes of different design have different efficiencies and cooling powers, the predetermined cycle times may vary with the design of the cryoprobe and the operating mode of the cryoprobe.
These time periods may be varied to accomplish other regimens falling under the general description of two freezing cycles comprising creation of an iceball having a −20° C. isotherm substantially engulfing or coincident with the lesion, with a warming period between the freezing cycles. It is specifically contemplated that they be adjusted to account for cryoprobes of differing cooling power or cryoprobes from different manufacturers, and that the lesion size ranges be condensed or expanded as clinical experience dictates.
While the preferred embodiments of the devices and methods have been described in reference to the environment in which they were developed, they are merely illustrative of the principles of the inventions. The elements of the various embodiments may be incorporated into each of the other species to obtain the benefits of those elements in combination with such other species, and the various beneficial features may be employed in embodiments alone or in combination with each other. Other embodiments and configurations may be devised without departing from the spirit of the inventions and the scope of the appended claims.
