RU2185102C1 - Method for treating seminomatous testicle tumors - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: method involves introducing 37-74 MBK 99Tc-colloid under the tunica albuginea of the testicle affected by tumor or into spermatic cord stump. Propagation paths are marked and radiation treatment is applied to the areas. EFFECT: enhanced effectiveness and low toxicity of treatment.

Description

 The invention relates to medicine, more specifically to oncology, and may find application in the treatment of malignant neoplasms of the testicle.

 Testicular tumors are relatively rare, accounting for 0.5-3% of all oncological diseases, but they occupy the 4th place among the causes of death from cancer of young men. As a rule, testicular cancer affects men of working age, the predominant age of patients from 20 to 40 years. The most common signs of a primary testicular tumor are pain, resizing, or swelling of the organ with the appearance of a tumor in it. These symptoms occur in 80-90% of patients. And although all the signs of a testicular tumor are evident, the delay in its diagnosis is due to the fault of the patient, who postpones the visit to the doctor. In this regard, 30-50% of patients with a testicular tumor entering the hospital already have metastases. Symptoms associated with the presence of metastases prevail over the symptoms of testicular damage - these are severe back pain, gastrointestinal upsets, weight loss, and sometimes a tumor is found in the abdominal cavity by palpation.

 Tumors of the testis are seminomic and non-seminomic.

 The most common (more than 50% of all germ cell tumors) are seminomic testicular tumors. In stages I and II of the disease, they affect mainly retroperitoneal lymph nodes, and with adequate treatment for such patients, a positive therapeutic effect is observed in 75-90% of cases. Distant metastases in seminoma tumors are much less common. These tumors are sensitive to both chemotherapy and radiation therapy (RT).

 Non-seminomic tumors are more aggressive, they metastasize early, not only to the lymph nodes, but also to the lungs, brain, liver, bones, and bone marrow. Non-seminomic tumors are insensitive to radiation therapy, only chemotherapy is used to treat them.

 The present invention relates to the treatment of seminoma tumors.

 They, as mentioned above, are sensitive to both chemo- and radiation therapy. In terms of effectiveness, these methods are almost equivalent, but radiation therapy is less toxic and, therefore, is currently being used more widely in the treatment of seminomic tumors in stages I and II of the disease.

 Detection of a testicular tumor is possible already upon examination of the patient, since the testicle becomes denser and increases in size. It is much more difficult to determine the state of regional metastasis zones. The closest lymph nodes, according to the WHO classification, are retroperitoneal, inguinal, and intralase. If inguinal lymph nodes are accessible by palpation, then it is necessary to use a tomographic examination to identify retroperitoneal and intra-pelvic lymph nodes, and depending on the equipment of the clinic, computer or magnetic resonance imaging is used. This allows you to detect an increase in lymph nodes and suggest the malignancy of their lesions, but only the histological examination of it confirms the nature of the tumor.

 Treatment of a testicular tumor begins with an orchofuniculectomy operation, and further therapy depends on a laboratory (blood test using tumor markers) and histological examination of the tumor. If metastases are detected or for the purpose of their prevention in stages I and II of the disease, chemotherapy courses or irradiation of the retroperitoneal lymph nodes are carried out, which, as mentioned above, in case of seminomic testicular tumors, are the primary zones of regional metastasis. In the III stage of the disease (the presence of distant metastases), combined chemoradiotherapy is most often carried out / Guide "Combined and complex treatment of patients with malignant tumors" edited by V.I. Chissova, M., Medicine, 1989, p. 448-449 /.

 Closest to the proposed is a method of treating patients with testicular seminoma, described in the Guide "Radiation therapy of malignant tumors" edited by prof. E.S. Kiseleva, M., Medicine, 1996, p. 315-319.

 The method consists in the fact that after orchifuniculectomy, LT is performed either as an adjuvant (prophylactic) effect, or as a means of causing the destruction of macroscopic metastases.

 When irradiating patients with stage I diseases, paraaortic lymph nodes and iliac nodes on the side of the tumor location are included in the radiation exposure zone. Usually 4 oncoming fields (front and back) or two L-shaped fields are used. The upper boundary of the fields is between THP and L1, the width of the fields is 8-9 cm.

 With a seminoma of stage II, the volume of radiation exposure is increased due to the inclusion of opposite iliac lymph nodes in the treatment area, and 2-4 weeks after the end of irradiation of the abdominal cavity, adjuvant radiotherapy begins on the lymph nodes of the mediastinum and supraclavicular region.

 According to the authors of the prototype method, as well as according to other authors, as a result of treatment for 5 years, 93-100% of patients with stage I disease and 87-93% with stage II live.

 However, it was noted in (p. 316) that with the used volume of radiation exposure, errors are possible when choosing the radiation fields. So, using a stimulator, it was found that in 8% of patients not all groups of lymph nodes located in the area of the most likely metastasis fell into the radiation exposure zone. In addition, the inclusion of adjuvant radiation in the stage II disease of the mediastinal lymph nodes and supraclavicular region is considered by some authors to be unjustified, based on data obtained from a large number of clinical observations, which showed that additional radiation exposure does not improve treatment results, but significantly increases toxic effect on the body.

 Thus, RT according to the prototype method is 10-15% ineffective, and with unreasonable expansion of the irradiation zone is quite toxic.

 The technical task of the present invention was to increase the effectiveness of treatment and reduce toxicity due to an adequate RT.

 This problem is solved in that in the known method for the treatment of seminomic testicular tumors, including surgical removal of the primary tumor site, tomographic examination of the abdominal cavity and small pelvis and subsequent radiation therapy of the regions of regional metastasis, according to the invention, additionally under the protein membrane of the tumor affected testicle before surgical removal of the tumor site or 37-74 MBK of 99Tc-colloid are injected into the stump of the spermatic cord after surgical intervention, the ways of its distribution and Teaching effect on these areas.

 Studying for many years RT of testicular tumors, we noticed that the absence of a positive therapeutic effect of RT in patients was usually associated with anomalies in the development of their urogenital system or in cases of previous operations on the scrotum, pelvic organs, and in retroperitoneal areas. This served as the basis for paying special attention to these facts when collecting an anamnesis and examining a patient. It is known, for example, that in 8% of men, due to individual characteristics, lymph drainage from the right testicle is directed to the retroperitoneal lymph nodes on the left. It is also known that in childhood, boys often (up to 2%) have cryptorchidism - an undescended testicle in the scrotum. According to various authors, this fact increases the risk of testicular cancer by about 5 times compared with the population. This risk becomes significantly higher (more than 10 times) in men with bilateral cryptorchidism. Performing orchidhexia (testicular reduction) at 5-10 years of age significantly reduces this risk [Abstract of the conference "Germ cell tumors of the testis: biology, clinic, diagnosis and treatment", M., March 2-3, 2000, pp. 10-11] .

 At the same time, according to our observations, orchipexia, as well as operations on the organs of the scrotum, inguinal canal and pelvis, unpredictably change the direction of lymphatic outflow from the testicles. This, in our opinion, explains the decrease in the effectiveness of radiation therapy according to the generally accepted technique, including by the prototype method.

 This prompted us to examine the pathways of lymphatic drainage from the affected testicle in each patient. For this purpose, we used radiopharmaceuticals, in particular, 99Tc, although it is known from the literature that radionuclide methods for the diagnosis of affected lymph nodes are ineffective and have no practical value [Guide "Combined and complex treatment of patients with malignant tumors" edited by V.I. Chissova , M., Medicine, 1989, p.448].

 Research Shiryaeva S.V. [Abstracts of the conference "Possibilities of modern radiation diagnostics in medicine", M., 1985, p.142-143], devoted to scintigraphy with 67Ga-citrate in the differential diagnosis of metastasis of testicular tumors into retroperitoneal lymph nodes, and Matveeva B.P. [Abstract of the Ph.D. thesis "Lymphography in urooncological diseases", 1968] on the implementation of lower lymphoscintigraphy with 99Tc can not be called specific methods, since neither 67Ga nor 99Tc are tumor drugs. Moreover, intravenous administration of 67Ga - citrate provides visualization of retroperitoneal lymph nodes larger than 5 cm, and with lower indirect lymphoscintigraphy with 99Tc-colloid, only external lymphatic collectors (inguinal, external iliac, paraaortic) above the renal pedicle can be visualized. The remaining retroperitoneal lymph nodes are not visible.

 We first made an attempt to introduce 99Tc-colloid under the white membrane of a tumor affected testicle before surgical removal or into the stump of the spermatic cord, if the patient had previously undergone an orchiectomy. Since it is known that tumor cells spread through the lymphatic vessels, we decided to see how the 99Tc-colloid distribution pathways would be visualized through them, which, in our opinion, would correspond to the path of lymphatic outflow from the testicle and, therefore, the tumor cells entering it into the corresponding lymph nodes . Our assumptions were confirmed - those lymph nodes were visualized, which corresponded to the lymphatic vessels coming from the testicle, in accordance with their anatomical orientation. This, in turn, provided us with the possibility of forming a field of radiation exposure depending on the accumulation of 99Tc colloid, i.e. conducting targeted RT to those lymph nodes that could be or were involved in the metastatic process.

 The use of orchifuniculoscintigraphy with 99Tc-colloid is especially important because a tomographic examination reveals only an increase in lymph nodes, which is a non-specific indirect sign of their malignant lesion. If it does not detect their increase, then this nevertheless does not reliably mean their non-involvement in the malignant process. The determination of the pathways of lymphatic drainage using a 99Tc colloid, as shown by us, increases the reliability of the detection of metastasis.

 Our observations of patients with seminomic testicular tumors, including with abnormal lymphatic drainage (7 people) indicate that the proposed tactics of RT provides all without exception, relapse-free survival for 3 years, and patients continue to be observed.

 The essence of the method is illustrated by examples.

 EXAMPLE 1. B. M., 1967 R. , And / b 1976, was admitted to the clinic TsNIRRI 09/09/98. with a diagnosis of testicular seminoma.

 From the anamnesis: 2 months before admission to the clinic, the patient noted an increase in the size of the right testicle. I went to the clinic at the place of residence a month later. Ultrasound examination (ultrasound) revealed a change in the structure of the testicular tissue and revealed a neoplasm on the right. 08/20/98 the patient was operated on in the Oncology Research Institute named after Petrova about a neoplasm of the abdominal cavity - a conglomerate of lymph nodes was detected, a histological examination of which showed the presence of spermatocytic seminoma. The patient was referred to TsNIRRI for further examination and treatment.

 On admission: complaints of pain in the lumbar region and in the right testicle.

 According to MRI (magnetic resonance imaging) of the abdominal cavity and pelvis from 09/10/98. - conglomerate of retroperitoneal lymph nodes of size 8 • 12 cm with compression of the ureter of the right kidney, hydronephrotic deformation of the right kidney, an increase in intrathoracic lymph nodes to 2 cm. Change in the structure of the right testicle - a suspicion of a tumor.

 09/11/98 Orchifunicular scintigraphy was performed (37 MBC of 99Tc-colloid was introduced under the white membrane of the right testicle) - 99Tc was accumulated in the testis and in the area of intrathoracic lymph nodes, a block in the area of para-aortic lymph nodes. The change in lymphatic drainage is regarded as a consequence of the operation performed on 08/20/98.

 The study using tumor markers: LDH (lactate dehydrogenase) - 736 (normal 170-480), AFP (alpha-fetoprotein) - 2 (normal to 5), hCG (human chorionic gonadotropin) - 76 (normal to 10).

 CT (computed tomography) of the lungs - without pathology.

 Based on the examination, the diagnosis was established: cancer of the right testicle, ur T • N3Mo (stage 2).

 The patient was offered an operation - an orchifuniculectomy on the right. 09/15/98 the operation was performed - the right testicle with spermatic cord was removed. Histological examination revealed a seminorm-dysgerminoma (biopsy O-122981-86), a study of the conglomerate of lymph nodes revealed metastasis of the seminoma-dysgerminoma (K-123022).

 Final diagnosis: cancer of the right testicle - T2N3Mo seminoma.

 09/27/98 RT was started on the area of retroperitoneal and intrathic lymph nodes on the right of 2 Gy per day daily 5 times a week to a total dose of 46 Gy. Clinical and biochemical blood tests were performed every week - a marked decrease in indicators (hemoglobin, red blood cells, white blood cells, platelets) did not require additional correction. During the entire course of RT, the patient received vitamins, actovegin, iron preparations, hilak-forte.

 11.16.98 the patient was discharged from the clinic in satisfactory condition under the supervision of an oncologist at the place of residence with the appearance for a follow-up examination after 2 months.

 1/12/99 at the control examination, the patient's condition is satisfactory, no complaints, no pain.

 According to the results of ultrasound, there was an increase in the lymph node in the region of the right renal leg up to 2.5 cm.

 According to MRI, there is a single enlarged paracaval lymph node on the right, 2.2 cm in size, intratase lymph nodes up to 1 cm. Fibrously changed tissue in the form of a strand in the retroperitoneal region on the right. Conclusion MRI: the dynamics of the process compared with the data from 09/10/98. positive.

 Data of tumor markers: AFP - 2 (normal), LDH - 420 (normal), hCG 6 (normal).

 Subsequently, every 3 months, the patient was observed at the TsNIRRI polyclinic, undergoing outpatient studies, including ultrasound, MRI and tumor markers - 6 months after the treatment, complete remission was noted (all lymph nodes up to 1 cm). Relapse-free remission to date is more than 2.5 legs, the patient continues to be observed.

 EXAMPLE 2. B. Sh., B. 1954 And / b 434, was admitted to the clinic TsNIRRI 02/17/98. with a diagnosis of seminoma of the right testicle.

 From the anamnesis: considers himself ill since January 1997, when he first began to note an increase in the right testicle. Long-term treatment was carried out for inflammatory testicular diseases, but the condition was constantly worsening. Pain appeared and began to intensify, weakness increased. The patient turned to the Medical Unit No. 70, where he underwent lower indirect lymphoscintigraphy with 99Tc, and although it did not reveal any pathology, 01/15/98. the patient underwent an orchiectomy on the right. Histological examination revealed a seminoma. The patient for aftercare was sent to TsNIRRI.

 On admission: complaints of weakness.

 02/19/98 performed ultrasound pathology - not detected.

 According to CT results, there were no signs of pathological changes in the abdominal organs; a lymph node 1.2 cm in size was detected retrovasively in the pelvic cavity. Lungs without pathology.

 03/12/98 Lymphatic funicular scintigraphy was performed - 74 MBC of 99Tc-colloid were introduced into the stump of the spermatic cord. The accumulation of the radiopharmaceutical was noted in the pelvic cavity, i.e. lymphatic drainage to the lymph nodes of the pelvis.

 Tumor markers: hCG - 5.9 (normal to 15), AFP - 2.8 (normal to 10), LDH - 520 (normal to 450).

 When revising the histological material confirmed seminoma dysgerminoma (K-118676-691 from 02/18/98).

 Based on the examination, the diagnosis was established: cancer of the right testicle (seminoma), ur T1NoMo (stage 1).

 From 04/21/98 RT was started in the regimes similar to Example 1, up to an SOD of 36 Gy to the area of intrathoracic lymph nodes on the right and the stump of the spermatic cord.

 06/08/98 the patient was discharged from the clinic with a control attendance at the institute after 3 months.

 09/10/98 during the control examination - the condition is satisfactory, no complaints. According to an objective examination - without features.

 According to ultrasound, MRI and tumor markers - complete remission.

 In the future, the patient was examined every 3 months - to the present he is in remission, which is about 3 years.

 The proposed method to date, 16 people have been treated, of which there were 7 patients with abnormal lymph drainage, all with stage I or II seminoma. Relapse-free survival for all ranges from 3 months (patients continue to be observed) to 3 years.

 The method in comparison with the known has several advantages.

 1. Effective in 100% of patients with seminoma of I and II stages of the disease due to targeted RT, while known methods of treating testicular seminoma are ineffective in 10-15% of patients.

 2. The method is less toxic for the patient’s body, since radiation exposure is directed only to the lymph nodes involved in the metastatic process.

 The method was developed in the department of operative and endovascular urology of TsNIRRI and passed clinical testing in 16 people with a positive result.

Claims (1)

 A method of treating seminomic testicular tumors, including surgical removal of the primary tumor focus, tomographic examination of the abdominal cavity and pelvis and subsequent radiation therapy of regional metastasis zones, characterized in that it is additionally under the white membrane of the testis affected by the tumor before surgical removal of the tumor focus or in the stump of the spermatic cord after 37-74 MBK of 99Tc-colloid are injected with surgical intervention, the pathways of its distribution are noted, and radiation exposure is carried out on these zones.