RU2576875C1 - Method for planning high-dose interstitial radiotherapy of prostate cancer - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method involves saturation biopsy of prostate through the perineum by means of a complex designed for ultrasound-navigated needle insertion into prostate regions. That is combined with targeted sampling of biopsy materials from a paraurethral region on both sides and on the underside of the urethra. If observing neoplastic changes in the paraurethral region, radiation doses are specified up to 100-120 Gy for the entire capacity of the prostate, including the paraurethral region. If no changes are observed, radiation doses are up to 70-80 Gy to cover the paraurethral region of the prostate, and intrastat needles are inserted laterally to the urethra.

EFFECT: method enables optimising the radiation load distribution throughout the prostate while conducting the high-dose prostate brachytherapy, receiving the reliable information on the neoplastic process extent in the paraurethral region, which is ensured by sampling the biopsy materials from the prostate and paraurethral region, choosing the optimum radiation doses, inserting intrastat needles taking into account the presence or absence of tumour cells.

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Description

The invention relates to medicine, namely to surgical oncology, and can be used for planning high-dose interstitial radiation therapy for prostate cancer (PCa).

The widespread introduction in clinical practice of modern organ-preserving methods of treating patients with prostate cancer (high-dose and low-dose brachytherapy, treatment with highly focused ultrasound, cryotherapy, etc.) presents new requirements for the method of prostate biopsy. Obtaining tissue samples, aimed mainly at histological verification of the diagnosis, should also play an equally important role in choosing a treatment method and help optimize the treatment plan for each individual patient.

To date, performing a biopsy of the prostate (RV) under ultrasound guidance is a mandatory diagnostic standard and an essential element in determining the degree of local prevalence of the process. According to the current recommendations of leading urological and oncological associations (EAU 2014, NCCN 2014), the generally accepted biopsy technique involves taking 12 tissue columns predominantly by transrectal access. At the same time, in a number of clinical situations, such as: a prostate-specific antigen (PSA) level of less than 10 ng / ml, a large volume of the gland, a history of primary negative biopsies, it becomes necessary to perform a saturation biopsy (more than 18 biopsies).

The saturation biopsy technique was first described for transrectal access at the very beginning of the 21st century (Borboroglu PG, Comer SW, Riffenburgh RH, Amling CL Extensive repeat transrectal ultrasound guided prostate biopsy in patients with previous benign sextant biopsies // J. Urol. - 2000. - Vol. 163, N 1. - P. 158-162.). Attempts to use brachytherapeutic equipment that allows percutaneous perineal access to the gland in order to obtain material for pathomorphological studies are also associated with relatively recent studies. The advantages that this type of access provides are obvious: the possibility of an adequate intake of material from the apical and anterior area of the gland, a high level of accuracy in obtaining the material through the use of an ultrasound probe fixed on the stepper and a brachytherapeutic lattice. At the same time, perineal access to a greater extent than transrectal requires standardization in questions of dividing the gland into sectors (quadrants), which serves as the basis for systematicity when performing this type of procedure.

The vast majority of authors when performing saturation perineal biopsy (SPB) divide the gland from 8 to 24 zones (quadrants) (Li N., Yan W., Zhou Y., Ji Z., Chen J. Transperineal ultrasound-guided saturation biopsies using 11- region template of prostate: report of 303 cases // Urology. - 2007. - Vol. 70, No. 6. P. 1157-1161; Merrick GS, Gutman S., Andreini H. et al. Prostate cancer distribution in patients diagnosed by transperineal template-guided saturation biopsy // Eur Urol. - 2007. - Vol. 52, No. 3. - P. 715-723 .; Moran BJ, Braccioforte MH Stereotactic transperineal prostate biopsy // Urology. - 2009. - Vol. 73 , No. 2. - P. 386-388.).

An analysis of the available data suggests that the creation of new modifications of St. Petersburg is aimed at solving the following main tasks: increasing the diagnostic effectiveness of the procedure, reducing the frequency of detection of clinically insignificant cancer, identifying multifocal cases of the disease when determining candidates for focal, primarily ablative, treatment methods (Singh P .V., Anele S., Dalton E. et al. Prostate cancer tumor features on template prostate-mapping biopsies: implications for focal therapy // Eur. Urol. - 2014. - Vol. 66, No. 1, - P. 12 -19.).

There are no studies aimed at optimizing the performance of a saturation biopsy in order to conduct more radical methods of treatment, such as surgical treatment or interstitial radiation therapy.

Interstitial radiation therapy (brachytherapy) is a highly effective treatment for patients with prostate cancer. Modern methods of visualization and planning of radiation exposure make it the method of choice in many patients with localized and locally prevalent forms of the disease. There are two types of brachytherapy (BT): the more common low-dose and high-dose (VBT), which can be considered as the next stage in the development of this treatment method.

One of the significant advantages of VDBT in comparison with not only radical surgery, but also with alternative radiation techniques (low-dose brachytherapy, external radiation therapy) is a lower complication rate. The early (acute) urination disorders observed in patients in most cases pass independently or require short-term conservative therapy and do not significantly affect the quality of life of patients in the future (Kanaev S.V., Petrov SB, Nosov A.K. et al. Disorders of the function of the lower urinary tract during high-dose brachytherapy for prostate cancer // Oncology of the XXI century - from scientific research to clinical practice: Materials of the VIII Congress of Oncologists of Russia, St. Petersburg, September 11-13 I, 2013 - St. Petersburg: FSBI Research Institute of Oncology named after N.N. Petrov of the Ministry of Health of Russia - S. 844.).

However, the frequency of late complications from the lower urinary tract, according to some authors, remains at a relatively high level. So, Hindson B.R. et al. report a total risk of 8.2% of the formation of urethral stricture over the next 2 years after CBT (Hindson BR, Millar JL, Matheson B. Urethral strictures following high-dose-rate brachytherapy for prostate cancer: analysis of risk factors // Brachytherapy. - 2013. - Vol. 12, No. 1. - P. 50-55.). Moreover, depending on the absorbed dose, this frequency varied from 2.3% (18 Gy / 3 fractions) to 31.6% (20 Gy / 2 fractions). The most frequent localization was determined by the bulbous-membranous department (50.0%). Most researchers provide data indicating that the average level of the frequency of formation of urethral stricture during VBD in various modes is about 15% (Pellizzon A.S., Salvajoli JV, Maia M.A. et al. Late urinary morbidity with high dose prostate brachytherapy as a boost to conventional external beam radiation therapy for local and locally advanced prostate cancer // J. Urol. - 2004. - Vol. 171, No. 6. - P. 1105-1108.).

The most important technical feature of VDBT is the ability to create ideal conditions for controlled uneven pancreatic irradiation with the exact addition of additional radiation doses (“boost”) to areas with a high risk of recurrence of prostate cancer - an imaged tumor, peripheral zone, and at the same time reduce radiation exposure to surrounding normal tissues, primarily the prostatic part of the urethra (Hoskin PJ, Colombo A., Henry A. et al. GEC / ESTRO recommendations on high dose rate afterloading brachytherapy for localized prostate cancer: an update // Radiother. Oncol. - 2013. - Vol. 107, No. 3. - P. 325-332.).

The specified method of VDBT recommended by the European Association GEC-ESTRO, is the closest analogue of the invention.

However, due to the lack of accurate data on the localization of the tumor process in the pancreas, the authors recommend uniform irradiation of the entire pancreas, including the urethra, which significantly increases the risk of complications of radiation treatment from the urinary tract, especially when using single exposure.

On the contrary, a decrease in the radiation load on the urethra in the absence of accurate data on the topography of the tumor of the pancreas can lead to a significant increase in the risk of tumor recurrence due to unrecognized damage to the central lobe of the pancreas.

The technical result of the invention is to optimize the distribution of radiation load within the pancreas during high-dose brachytherapy of the pancreas due to reliable information about the prevalence of the tumor process in the immediate vicinity of the urethra (paraurethral zone).

The specified technical result is achieved by the fact that in the method of planning high-dose interstitial radiation therapy for prostate cancer (pancreas), including saturation biopsy of the pancreas with subsequent planning of radiation exposure to the pancreas, the area of tumor lesion of the pancreas and the prostatic part of the urethra, according to the invention when performing saturation biopsy of the pancreas with perineal access with the help of a complex designed for ultrasound-guided needle insertion into the pancreas, additionally carry out targeted bi ptats from the paraurethral zone on both sides and below the urethra and in the presence of tumor changes in the paraurethral zone, radiation doses of up to 100-120 Gy for the entire pancreas volume are selected, including the paraurethral zone, and in the absence of such changes, radiation doses to the pancreatic paraurethral zone up to 70 are chosen -80 Gy and carry out the lateral introduction of intrastatal needles with respect to the urethra.

Transperineal (perineal) sampling of biopsy specimens is performed under spinal anesthesia under operating conditions under aseptic conditions.

During the procedure, a standard 2-dimensional transrectal ultrasound imaging of the pancreas is performed using a specialized sensor with its position encoder on a holder stand equipped with a calibrated brachytherapeutic grate (template) designed to navigate invasive procedures (insertion of needles during biopsy, brachytherapy or the introduction of radiocolloids) .

Special software allows you to combine a calibrated image of the grating with transverse ultrasound scans of the pancreas in real time. Such an approach provides the ability to accurately visualize the intraprostatic section of the urethra and the paraurethral zone of the gland.

In the course of performing a standard saturation biopsy with perineal access, biopsy samples are taken from the paraurethral zone. The amount of these biopsy specimens depends on the volume of the prostate.

The material obtained for the pathomorphological examination obtained during the procedure is subject to mandatory labeling in accordance with the biopsy specimen collection scheme.

Reliable information on the presence or absence of tumor cells in the biopsy specimens obtained from the paraurethral zone allows the most optimal planning of the introduction of intrastatal needles, determining the boundaries of the boost radiation zone during high-dose brachytherapy.

In FIG. 1 shows a schematic arrangement of intrastatic needles superimposed on a transverse ultrasound scan of the pancreas: the intrastats are located at a sufficient distance from the urethra.

           In FIG. 2 shows a schematic arrangement of intrastatal needles superimposed on a transverse ultrasound scan of the pancreas: the intrastatics to the left of the urethra are located next to the urethra. Their location corresponds to the topography of positive paraurethral columns.

In FIG. Figure 3 shows the scheme for biopsy sampling from the paraurethral zone: a) a transverse pancreatic scan combined with a calibrated image (the distance between the nearest points is 5 mm) corresponding to the brachytherapy lattice, b) scheme for sampling paraurethral biopsy samples (marked with circles). The opening of the urethra corresponds to D3, the projection of the urethra on the transverse scan is indicated by a dashed line.

The method is carried out, for example, as follows.

At the first diagnostic stage, a standard urological examination of the patient is performed, which includes determining the level of PSA, digital rectal examination, ultrasound examination of the pelvic organs. Indications for performing saturation biopsy of the pancreas with perineal access are determined.

A biopsy is performed according to the following procedure.

To perform our proposed method, it is necessary to have a specialized complex of VK Medical company (Denmark) for conducting two-dimensional transrectal scanning of the pancreas, an ultrasonic sensor with a frequency of 7.5 MHz, placed on a stand ("stepper") of a calibrated grating for introducing biopsy needles into tissue pancreas, biopsy gun company "Bard" (USA). Used biopsy needles should have the following characteristics: diameter - 18G, diameter of tissue column - 1 mm and depth of shot - 22 mm.

After performing spinal or epidural anesthesia according to the standard technique, the patient is placed on the operating table in a lithotomy position, bending and maximal dilution of the lower extremities are performed. A Foley Ch 16 urethral two-way catheter is inserted into the urethra. The catheter can is filled with the aid of Categel ^® foam solution (registration number 012477/01), which allows for more accurate visualization of the basal gland and the course of the catheter (urethral border) within it. Next, a transrectal ultrasound probe is inserted into the rectum. Perform two-dimensional scanning of the pancreas. The largest pancreas size is determined by scanning in the transverse plane. The resulting image is combined with a calibrated image (the distance between the nearest points is 5 mm) corresponding to the brachytherapeutic lattice.

The operation area (perineum, scrotum and posterior thigh) is treated with betadine solution.

After determining the boundaries of the gland and the urethra during transverse scanning, a graphic fixation of these structures is carried out on a brachytherapeutic lattice diagram, presented in printed form and which is necessary for subsequent documentary registration of the biopsy site. The image of the prostatic part of the urethra for standardization of biopsy, as a rule, is installed in the center of the lattice and corresponds to the sagittal plane having the letter value D. Next, biopsy samples are collected. The control of the introduction of the needle into the tissue of the prostate is performed by scanning in the longitudinal plane in real time. With large sizes of the gland (basal-caudal distance exceeds 20 mm), obtaining tissue from one point is carried out in two stages: the first injection - taking tissue from the apical portions of the gland, the second injection is carried out from the same point after the preliminary injection of the needle to the distal border of the previous entrance of the needle in pancreatic tissue. Such a technique allows one to obtain material for pathomorphological research throughout the pancreas, including from its bedless, elusive departments. The decisive step in conducting a biopsy using this technique is to obtain biopsy samples from the paraurethral zone on both sides and below the urethra. All biopsies obtained are labeled (receiving side, apical or basal localization). Separately labeled biopsy specimens obtained from the paraurethral zone. The presence (absence) of tumor cells in biopsy specimens obtained from the paraurethral zone makes it possible to most optimally plan the introduction of intrastatal needles, to determine the boundaries of the boost radiation zone during high-dose brachytherapy.

The method is illustrated by the following clinical examples:

Example 1. Patient S., 67 years old, was admitted to the hospital with a diagnosis of pancreatic neoplasm of an uncertain nature. Given the low preoperative PSA level of 5.2 ng / ml, a saturation biopsy of the pancreas with perineal access is recommended. During the biopsy, 30 biopsy specimens were taken, including from the paraurethral zone (7 biopsy specimens). A subsequent pathomorphological study showed the presence of acinar pancreatic adenocarcinoma in 5 of 30 columns, the sum of Gleason 7 (3 + 4). All columns containing adenocarcinoma were obtained from the left lobe. No tumor cells were found in biopsy specimens obtained from the paraurethral zone. Upon further clinical and instrumental examination (pelvic MRI with contrast, osteoscintigraphy of the skeleton bones in the SPECT-CT mode), data for the spread of the tumor process outside the organ were not obtained. A clinical diagnosis of T2 in N0M0G2 has been made. According to the NCCN classification, the patient is assigned to the intermediate prognosis group. Indications are formulated for VDBT in mono mode (3 fractions of 11.5 Gy each). During the session, the introduction of the needle insertion needle was carried out taking into account the absence of involvement in the process of the paraurethral zone in order to reduce the likelihood of radiation damage to the urethra (Fig. 1).

Example 2. Patient W., 58 years old. The preoperative PSA level is 7.1 ng / ml. During saturation biopsy of the pancreas with perineal access, 35 biopsy specimens were taken, including from the paraurethral zone (8 biopsy specimens). Histological conclusion: acinar pancreatic adenocarcinoma in 12 of 35 columns, Gleason total 6 (3 + 3). Positive bars are obtained from both lobes. In 2 of 8 biopsies from the paraurethral zone (left), adenocarcinoma was detected. Based on the results of a standard examination, a clinical diagnosis of T2 with N0M0G1 was made. According to the NCCN classification, the patient is assigned to the intermediate prognosis group. Indications are formulated for conducting HPH in mono mode (3 fractions of 11.5 Gy) (Fig. 2).

An analysis of the results of using the proposed method for high-dose interstitial radiation therapy for prostate cancer showed that the absence of morphological signs of the presence of a tumor process in the paraurethral zone in 21 of 23 patients allowed us to reduce the radiation load on the urethra by 20%. None of these patients showed complications from the urethra and bladder.

The proposed method allows for detailed mapping of morphological information about the topography of the foci of prostate cancer and use the information obtained to conduct VBT. For the first time, a method has been proposed that, when conducting VBT, allows dosimetric planning and the introduction of intrastatal needles taking into account the presence or absence of tumor cells in the immediate vicinity of the urethra, which allows in 90% of cases to reduce the radiation load on the urethra and to reduce the number and severity of adverse effects radiation treatment.

Claims (1)

A method for planning high-dose interstitial radiation therapy for prostate cancer (pancreas), including saturation biopsy of the pancreas with subsequent planning of radiation exposure to the pancreas, the area of tumor of the pancreas and the prostatic part of the urethra, characterized in that when performing saturation biopsy of the pancreas with perineal access using a complex designed for ultrasound-guided introduction of needles into the pancreas, an additional biopsy specimen is taken from the paraurethral zone on both sides and from below urethra and in the presence of tumor changes in the paraurethral zone, radiation doses of up to 100-120 Gy for the entire pancreas volume are selected, including the paraurethral zone, and in the absence of such changes, radiation doses for the pancreatic paraurethral zone up to 70-80 Gy are selected and lateral injection of intrastatal needles is performed in relation to the urethra.

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