Cycles Of Polychemotherapy Research Articles

Therapy of chronic pain in cancer patients: Tafalgin use experience. Case report

Background. Chronic pain is the most common and severe condition associated with cancer, causing peripheral and central nervous system disorders Inadequate pain control can be destructive and negatively affect patients' quality of life and daily activity. Therefore, developing new drugs for complete pain control during antitumor therapy and palliative care is an urgent problem in modern oncology. One of these directions is the search for selective molecules that interact with 1-opioid receptors without many side effects of opioids.
 Aim. To evaluate the effectiveness of a new selective 1-opioid analgesic, Tafalgin, in treating chronic pain in a patient with pancreatic cancer.
 Materials and methods. Tafalgin was used to control chronic pain in a 60-year-old patient with stage IV pancreatic cancer, pT2 N0M1, with liver metastases, state after 10 cycles of polychemotherapy, and distal subtotal resection of the pancreas with splenectomy, progression in October 2022, liver metastases; state after 4 cycles of polychemotherapy, severe chronic pain.
 Results. The initial pain severity was evaluated using a visual analog scale: 7 points at rest and 9 points on exertion. The patient developed pain during FOLFIRINOX polychemotherapy, for which he received tramadol at a daily dose of 400 mg in combination with paracetamol, with an effect for 1.5 months. The pain severity increased with breakthrough pain. The patient was prescribed long-acting morphine at 60 mg/day, with good effect. However, the patient experienced nausea and vomiting. The morphine dose was reduced to 20 mg, thus resolving side effects and decreasing the effectiveness. Tafalgin was administered at a dose of 4 mg TID. The pain severity decreased to 11.2 points. No adverse events were reported. The patient has been receiving the drug for 52 days. His sleep and appetite have improved, physical activity has increased, and no weight loss has been reported.
 Conclusion. When switching a patient to Tafalgin, continuous adequate pain control is maintained, not inferior to morphine. Tafalgin is associated with a favorable safety profile.

Radiation-induced soft tissue sarcoma of the neck after radiation therapy for Hodgkin's lymphoma: a clinical case

Background. Radiation-induced malignancies are one of the long-term complications of radiation therapy, which is widely used to treat some tumors. The latency period before a second tumor develops varies from 3 to 60 years. Epithelial tumors and hemoblastoses occur after low-dose radiation therapy and sarcomas after high-dose radiation therapy.
 Aim. To present a case of radiation-induced soft tissue angiosarcoma of the neck after the cure of Hodgkin's disease.
 Materials and methods. A 41-year-old patient with Hodgkin's nodular lymphoma with the lymphoid predominance of stage IIIA with involvement of the right cervical and clavicular lymph nodes, mediastinum, and abdominal lymph nodes was followed-up. In 2004 the patient underwent four cycles of polychemotherapy per ABVD regimen followed by radiotherapy of the right cervical and clavicular lymph nodes and mediastinum, with a total focal dose of 40 Gy.
 Results. Seventeen years after the treatment for Hodgkin's disease, including radiation therapy, the patient presented with painful swelling of the neck soft tissues in the radiation area with the transition to the anterior thoracic wall and an enlarged cervical lymph node. A lymph node dissection was performed. According to the combined positron emission tomography and X-ray computed tomography (PET/CT), histological and immunohistochemical studies, epithelioid angiosarcoma of soft tissues of the neck and thoracic wall stage IV cT2N1M1G3 with metastases to the skeleton bones, neck lymph nodes, left adrenal gland was established. Surgical treatment was not performed due to advanced disease. The patient received six cycles of polychemotherapy with doxorubicin + ifosfamide. PET/CT confirmed partial tumor regression.
 Conclusion. Radiation-induced soft tissue sarcoma is a late iatrogenic complication of radiation therapy for Hodgkin's lymphoma. The tumor occurred in the radiation area. PET/CT is the method of choice in diagnosing and evaluating the extent of cancer and response to treatment. Chemotherapy, as an option for complex treatment, can achieve adequate disease control when surgery is not feasible.

EVALUATION OF THE EFFICIENCY OF ALPHA-LIPOIC ACID AND IPIDACRINE HYDROCHLORIDE FOR THE PREVENTION OF PACLITAXEL-INDUCED PERIPHERAL NEUROPATHY ACCORDING TO THE TOTAL NEUROPATHY SCORE.

To evaluate the efficacy of combination of alpha-lipoic acid and acetylcholinesterase inhibitor (ipidacrine hydrochloride) to prevent the development and improve the course of paclitaxel-induced peripheral neuropathy (PIPN) in patients with breast cancer according to the Total Neuropathy Score. 32patients with breast cancer T1-4N0-3M0received six cycles of polychemotherapy according to the AT scheme (paclitaxel, doxorubicin) or ET scheme (paclitaxel, epirubicin). Patients were randomized into two groups- without (group I) or with (group II) medication for prevention of neuropathy. A comprehensive neurological examination of patients was performed according to all ten parameters of the Total Neuropathy Score before chemotherapy, and after third and sixth cycles of chemotherapy. Each parameter was evaluated from 0 (no deficit) to 4 (no function/the most severe deficit). The scores obtained from the scale were summarized to obtain a total score from 0to 40. The use of alpha-lipoic acid in combination with an acetylcholinesterase inhibitor (ipidacrine hydrochloride) significantly reduces the symptoms and severity of PIPN. The manifestations of PIPN in patients of the control group were significantly more severe compared to the group in which the study drugs were used. The average severity of neuropathy after 3and 6cycles was 1.75and 2.62in groupI, and 1.12and 1.62- in group II, respectively (improvement by 15.75% (p < 0.05) and 25.00% (p < 0.001) after3and 6cycles). Proposed combination of alpha-lipoic acid and ipidacrine hydrochloride led to a statistically significant reduction in the severity of PIPN, and thus to improvement of the functional capacity and quality of life of patients.

Pulmonary toxicity induced by the use of bleomycin in patients with germ cell testicular tumors

Introduction. Pulmonary toxicity induced by bleomycin is a dangerous complication of polychemotherapy in patients with germ cell tumors. It occurs with a frequency of up to 46%, and in 14% of cases it is fatal.&#x0D; Aim. To present cases of pulmonary toxicity during polychemotherapy with the inclusion of bleomycin for testicular germ cell tumors.&#x0D; Materials and Methods. Two patients aged 43 and 33 years old with testicular germ cell tumors were under observation after orchifuniculectomy who underwent chemotherapy according to the BER scheme (bleomycin + etoposide + cisplatin) in the steady-state mode in 4 and 6 cycles respectively. Positron emission tomography combined with computer tomography (PET/CT) with 18F-fluorodeoxyglucose was performed when clinical symptoms appeared at the end of treatment.&#x0D; Results. Histologically, the tumor in a 33-year-old patient was a mixed tumor seminoma, embryonal cancer with teratoid cancer elements. Abdominal spiral computed tomography revealed metastases to retroperitoneal lymph nodes. In a 43-year-old patient, the tumor had the structure of fetal cancer with multiple metastases to the lungs, mediastinal lymph nodes and retroperitoneal lymph nodes. Six and four cycles of polychemotherapy according to the BER regimen were administered, respectively. The cumulative dose of bleomycin was 540 and 360 mg in 18 and 12 injections. Treatment was accompanied by the development of febrile neutropenia with G-CSF correction. These risk factors should be considered the most significant. The appearance of respiratory symptoms during treatment should be regarded as a manifestation of pulmonary toxicity. PET/CT is the method of choice for diagnosis. The clinical picture in the observed patients, as well as changes on PET/CT, were detected 2 weeks after chemotherapy was completed.&#x0D; Conclusion. Pulmonary toxicity induced by the use of bleomycin in patients with germ cell testicular tumors is a very dangerous complication, sometimes with a lethal outcome. Therefore, its early diagnosis taking into account risk factors is of great importance in clinical practice. Among medical imaging methods, a special role is played by PET/CT, which allows predicting toxicity before the clinical and radiological debut.

Management of a patient diagnosed with ovarian cancer during pregnancy

Insufficient diagnosis of ovarian tumors during pregnancy and decreased oncological alertness constitute huge problems that can subsequently have an unfavorable outcome for both the pregnant woman and the fetus. The difficulties of diagnosing and treating ovarian cancer during pregnancy were demonstrated on the following clinical case example. In pregnant patient A. at 19-20 weeks of pregnancy, a lesion was found in the area of the right appendages (100.9 55.4 93.4 mm, V = 273 cm3), with many tissue partitions and parietal tissue inclusions. The growth of the neoplasm was noted (CA-125 884 U / ml) and the pain syndrome occurred in the patient at 23-24 weeks of pregnancy. Magnetic resonance imaging revealed a solid-cystic neoplasm of the right ovary (cystadenoma?) and surgery was performed in November 2019. Based on the results of histological examination, a high-grade serous ovarian cancer was diagnosed without signs of microsatellite instability MSI-H/dMMR (in the right ovary, in the biopsy of the left fallopian tube). The patient. received two cycles of polychemotherapy (TC scheme). The treatment was tolerated satisfactorily (CA-125 287.3 U / ml). At a gestational age of 34 6/7 weeks (January 2020), a simultaneous operation was performed, including a lower midline laparotomy, a lower uterine segment caesarean section, extirpation of the uterus with appendages, and an omentectomy. A boy was born (weight 2280 g, height 44 cm) with the Apgar score of 7/7 points, with no complications noticed in the postpartum period. Postoperative histological examination showed metastasis of carcinoma in the left ovary with signs of therapeutic pathomorphosis. The treatment was completed in March 2020 after six cycles of polychemotherapy.

Epidural compression in infants less than 6 months of life with neuroblastoma: experience of Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

Neuroblastoma (NB) can manifest through neurological symptoms caused by tumor extension into the spinal canal and the resulting epidural compression (EC). Clinical symptoms and management in patients with epidural compression depend on its level and duration, the severity of spinal cord compression, the patient's age and other factors. One of the biggest challenges is the diagnosis and treatment of EC in infants in the first months of life. Our retrospective analysis included 13 patients with NB complicated by spinal cord EC who had been diagnosed at the age of 0–6 months and treated at the D. Rogachev NMRCPHOI over the period from 01.01.2012 to 01.12.2018 (82 months). The study was approved by the Independent Ethics Committee and the Scientific Council of the D. Rogachev NMRCPHOI of the Ministry of Healthcare of the Russian Federation. The diagnosis of NB was based on the international diagnostic criteria. The tumors were staged in accordance with the INSS classification. The patients were stratified into risk groups and treated according to the modified NB-2004 protocol of the German Oncology Group. All the patients underwent diagnostic testing for neurogenic tumors as well as contrast-enhanced magnetic resonance imaging of the spinal cord with the assessment of the level of tumor invasion and the degree of spinal cord compression. The children were evaluated by a neurologist at admission and at follow-up visits. The median age at diagnosis of NB was 3.9 (0.5–6) months. At disease onset, 53.8% of patients had neurological symptoms, with motor deficiencies being the most common ones. In this group of patients, the median time from first neurological symptoms to diagnosis of NB was 1.56 months. Neurological symptoms at disease onset were not present or diagnosed at local healthcare facilities in 46.2% of infants. Extra-organic retroperitoneal primary tumors were found in 61.6% of patients; 30.7% of primary tumors were located in the posterior mediastinum, and 7.7% of primary tumors – in the lesser pelvis. No patients had MYCN-amplified tumors; in 1 case the MYCN gene status was evaluated as Gain; neither 1p nor 11q deletions were detected. The distribution of patients by INSS stages was as follows: stage 2 – 15.3%, stage 3 – 46.1%, stage 4 – 23.3% and stage 4S – 15.3%. The majority of patients (77.7%) were stratified into an observation group, the remaining patients (23.3%) were allocated to a medium risk group in accordance with the NB-2004 protocol. The level of tumor invasion into the spinal cord canal varied. Tumor invasion at the level of the cervicothoracic spine was observed in 15.4% of patients, at the level of the thoracic spine – in 15.4%, at the level of the thoracolumbar spine – in 46.2%, at the level of the lumbar spine – in 15.4%, and at the level of the sacral spine – in 7.7%. Neurosurgical intervention (laminotomy) was performed in 4 cases (30.7%). In one patient, laminotomy was the only treatment option (chemotherapy was not given). In two patients, neurosurgery was performed because of the deterioration of neurological symptoms caused by the start of the first polychemotherapy (PCHT) cycle. Chemotherapy was carried out in 92.3% patients. The patients from the observation group received 1–3 PCHT cycles (the median number of cycles was 2). Only one patient from the observation group did not receive PCHT. This patient underwent 2 surgeries. Currently, 10/13 (77%) patients are alive, 3/13 (33%) patients are dead (2/3 patients died of therapy-related infectious complications, and 1/3 – of acute heart failure in the early postoperative period). The median follow-up was 37.3 months. According to the assessment of late effects, neurological disorders were found in all the analyzed patients (n = 9), and orthopedic disorders were found in 66.6% (6/9) patients. The results of our analysis illustrate both the difficulty of diagnosis and management of EC in patients with NB and the need¬ for uniform testing and treatment standards with established follow-up and rehabilitation strategies for this group of patients.

Molecular Remission in PML/RARα-Positive Acute Promyelocytic Leukemia by Combined All-trans Retinoic Acid and Idarubicin (AIDA) Therapy

AbstractTwo hundred fifty-three patients with newly diagnosed acute promyelocytic leukemia (APL) were eligible to enter the multicentric GIMEMA-AIEOP “AIDA” trial during the period July 1993 to February 1996. As a mandatory prerequisite for eligibility, all patients had genetic evidence of the specific t(15; 17) lesion in their leukemic cells confirmed by karyotyping or by reverse transcription-polymerase chain reaction (RT-PCR) of the PML/RARα fusion gene (the latter available in 247 cases). Median age was 37.8 years (range, 2.2 to 73.9). Induction treatment consisted of oral all-trans retinoic acid (ATRA), 45 mg/m2/d until complete remission (CR), given with intravenous Idarubicin, 12 mg/m2/d on days 2, 4, 6, and 8. Three polychemotherapy cycles were given as consolidation. Hematologic and molecular response by RT-PCR was assessed after induction and after consolidation. At the time of analysis, 240 of the 253 eligible patients were evaluable for induction. Of these, 11 (5%) died of early complications and 229 (95%) achieved hematologic remission. No cases of resistant leukemia were observed. Of 139 cases studied by RT-PCR after induction, 84 (60.5%) were PCR-negative and 55 (39.5%) PCR-positive. One hundred sixty-two patients were evaluable by RT-PCR at the end of consolidation. Of these, 159 (98%) tested PCR-negative and 3 (2%), PCR-positive. After a median follow up of 12 months (range, 0 to 33), the estimated actuarial event-free survival for the whole series of 253 eligible patients was 83% ± 2.6% and 79% ± 3.2% at 1 and 2 years, respectively. This study indicates that the AIDA protocol is a well-tolerated regimen that induces molecular remission in almost all patients with PML/RARα-positive APL. Preliminary survival data suggest that a remarkable cure rate can be obtained with this treatment.

METHOD OF TREATMENT FOR ANAL CANCER AFFECTING THE SKIN

The extent of surgery for anal rectal cancer (ARC) is determined by the clinical efficacy of neoadjuvant chemoradiotherapy (CRT). An approach using medium intensity ultrasound combined with chemotherapy was developed. Advantages of sonodynamic chemotherapy (SD CT) were evaluated to improve the CRT efficacy and the quality of life of patients with ARC affecting the skin.Material and methods. 34 patients with morphologically verified сТ2–3N0–1M0 ARC received 2 cycles of polychemotherapy (PCT): intravenous bolus of mitomycin C 10 mg/m2 on days 1 and 29 + continuous infusion of 5-fluorouracil 1000 mg/m2 daily on days 1–4 and 29–32. Patients received CRT 3 weeks after the second PCT cycle. Prior to each session of standard external and intracavitary irradiation, 18 patients of the main group received a 2-hour extemporaneous mixture to the primary tumor site: 5 mg of the Coletex SP-1 hydrogel material with propolis based on sodium alginate plus 100 mg of gemcitabine-medac together with mid-frequency ultrasound (0.88 MHz, I =1.0 Вm/cm2, Patent No. 2638616). 16 controls received capecitabine 825 mg/m2 orally twice a day with 12-hour intervals during the radiation course.Results. Controlled general clinical effect after external irradiation + SD CT in the main group was 25.7 % (p&lt;0.05) higher than in controls, and complete regression was 1.4 times more frequent (77.8 % vs. 56.2 %). Radical surgery after CRT was necessary only in 11.1 % cases in the main group vs. 43.8 % in controls (p&lt;0.05). No local recurrences were observed during 612 months in 16 patients of the main group without surgery, while 22.2 % (p&lt;0.05) of controls showed local recurrence. The rates of pelvic relapses and distant metastases were similar in both groups.Conclusion. The positive effect of the proposed method for ARC treatment is determined by the combination of therapeutic factors including the action of a radiosensitizing agent introduced into tumor tissues.

Circulating tumor cells in patients with locally advanced breast cancer in evaluation of antitumor treatment efficacy.

e12064 Background: Circulating tumor cells (CTC) are of great importance in modern cancer research. Biological characteristics of CTC allow using them as tumor markers of high prognostic value. Their quantitative evaluation during treatment can be used to monitor the response to treatment in patients receiving systemic chemotherapy (CT). The purpose of the study was to assess the role of CTC in the prognosis of treatment efficacy in patients with locally advanced Her-2 negative breast cancer. Methods: The study included 42 patients aged 30-65 years with stage IIIA, IIIB, IIIC locally advanced Her-2 negative breast cancer, ECOG-WHO Performance Status from 0 to 2, Karnofsky Performance Status from 100% to 80%. CTC were determined using the CellSearch Veridex System (Johnson &amp; Johnson, USA), taking into account morphological characteristics and expression of epithelial cell adhesion markers EpCAM, CD45 and cytokeratins 8, 18 and 19. Results: CTC were found in 86% (36 of 42 patients) before treatment. CTC were not registered in 6 (14%) patients. 1 CTC was detected in 14% (6 patients); 2-3 CTC – 33% (14 patients); more than 3 CTC – 38% (16 patients). 12% (5) patients showed more than 10 CTC, with the maximum of 64 CTC in 1 patient. After 2 cycles of polychemotherapy, CTC were detected in 50% (21 patients). Other 21 patients did not show presence of CTC. Among CTC-positive patients, 1 CTC was detected in 4 patients (19%); from 2 to 3 CTC – in 9 patients (43%); more than 3 CTC – 8 patients (38%). 2 patients (10%) still showed more than 10 CTC – 28 and 33 CTC in the peripheral blood. After 2 cycles of polychemotherapy, the number of patients with more than 1 CTC decreased from 86% to 50%. Polychemotherapy regimen was changed for patients with increasing amounts of CTC. Conclusions: Determination of the CTC number allows evaluation of the treatment efficacy and is a specific marker for the change of applied polychemotherapy for such cancer type.

Dynamics of the immune status in patients with cervical cancer receiving complex treatment with dendritic cell vaccine.

e17005 Background: The purpose of the study was to determine the influence of complex treatment with dendritic cell vaccine on the dynamics of the immune status of patients with cervical cancer. Methods: 17 patients with cervical cancer (CC) T2b-4аN0-1M0-1 received chemotherapy with combined radiotherapy to the pelvic area. Between courses of cytostatic treatment, patients underwent dendritic cell vaccination (DCV) planned individually depending on the treatment effect, which was evaluated by the results of examination, US, CT and MRI. A control group included 19 patients with locally advanced CC receiving standard polychemotherapy (PCT) and radiotherapy. Immune status of patients was evaluated by flow cytometry (FACSCantoII BD) including T, B, NK cells, Tregs (CD4+CD25+CD127dim), memory T cells (Тm) and naïve T lymphocytes (Th0) was determined in the dynamics of the treatment. Results were calculated as a percentage from the total number of lymphocytes, for Tregs – in % from CD3+CD4+ cells, for Тm and Th0 – in % from CD3+CD4+ and CD3+CD8+ cells. Results: 1 to 4 cycles of PCT with DCV caused a transient increase in Tregs after the 1st cycle, with further regression to the initial levels; other studied lymphocyte subsets remained unchanged. Only after 8 or more DCV cycles, a favorable immunological dynamics developed; however, it was not observed in controls. DCV increased levels of lymphocytes with potential cytotoxicity: CD3+CD8+ (from 19.0±2.0 to 28.8±1.5%), NK cells (from 12.0±2.0 to 21.2±1.9%). During DCV courses helper-inducer Tm amount rose from 51.7±6.3 to 69.7±4.3%, while in remission – CD8+Tm grew from 28.5±2.1 to 40.4±5.3% (p &lt; 0.05 for all cases). Repeated DCV was satisfactorily tolerated by CC patients and, when used in complex treatment, caused a pronounced clinical effect. DCV did not lead to serious adverse events. Patients in remission are still observed. Conclusions: Treatment for CC with DCV causes a positive dynamics of the immune status, with the maximal effect after 8 and more DCV cycles. Remission is apparently maintained due to an increase in the level of TmCD8+ cells.

SINGLE-FACTOR LINEAR REGRESSION MODEL OF HODGKIN’S LYMPHOMA IN ADOLESCENTS

With the use of regression and dispersion analyzes conducted in this study it was possible to identify predictive factors that significantly worsen the prognosis of Hodgkin’s lymphoma in adolescents however constructed regression equations did not pass the quality assessment of the models, which did not allow them to be used for the construction of point and interval predictions. In a cohort of patients enrolled in the study a risk-adapted treatment program based on the risk group for stratification was conducted. Negative aspects of the results of our study could be related to the already selected volume of the program for these patients. In turn our analysis proves the validity of the selection of therapeutic loads (a number of cycles of polychemotherapy, doses of radiation therapy) depending on the risk group, into which the adolescent is stratified.

Relevance of Positron-Emission Therapy for Optimization of Treatment of Advanced Hodgkin’s Lymphoma Using Intensive ЕАСОРР-14 Program

Aim. To evaluate the relevance of the positron-emission therapy (PET) for optimization of the therapy of advanced Hodgkin's lymphoma (HL) using the intensive EACOPP-14 program. Materials &amp; Methods. 91 patients with advanced HL (IIX-IIE, III-IV) received the treatment according to the “ЛХМосква1-3” protocol over the period from November 2009 to February 2015, and then the treatment was analyzed. The median age was 29 years (range: 17-50); there were 42 men (46.3 %) and 49 (53.7 %) women. The treatment included 6 cycles of polychemotherapy according to the regimen ЕА(50)С0РР-14 ± radiation therapy. The radiation therapy was performed in 66 patients (72.5 %) after the completion of the chemotherapy. The cumulative focal dose was 30 Gy onto the areas of residual lesions and/or initially large tumor masses. Results. PET performed during the initial HL diagnosing permited to identify new areas of neoplastic lesions without changes in staging and treatment scheme, as well as specify areas and field size of planned radiation consolidation. The paper confirms the prognostic value of the intermediate PET in patients with advanced HL during the intensive first-line chemotherapy. The intensive therapy at the beginning of the treatment program is associated with higher chances for survival for patients with extremely unfavorable prognosis. After completion of the drug therapy, negative PET findings had a higher prognostic value, than the positive ones. The analysis of the relevance of residual tumor dimensions in the PET negative group demonstrated that the relapses were more common, if the residual tumor was more than 4.5 cm (according to CT findings). Conclusion. This study confirmed that it reasonable to discuss the discontinuation of the radiation therapy in patients with advanced HL, negative PET findings and small (&lt; 2.5 cm) residual tumor after the intensive ЕАСОРР-14 program. This tactics permits avoiding a number of delayed complications.

Therapy for primary mediastinal large B-cell lymphoma in accordance with the R-DA-EPOCH-21 program: The first results

to evaluate the efficiency of the R-DA-EPOCH-21 + R-DHAP protocol and autologous hematopoietic stem cell transplantation (a BEAM conditioning mode) in first-line therapy for primary mediastinal large B-cell lymphoma (PMBCL). In 2013 to 2016, the investigation enrolled 57 patients with newly diagnosed PMBCL (according to the 2008 WHO criteria). The results were analyzed in 40 patients who had completed their treatment. All the 40 patients (14 men and 26 women) (median age, 27 years (19 to 67 years)) received 6 cycles of polychemotherapy (PCT) in accordance with the R-DA-EPOCH-21 regimen. After induction PCT cycles, 32/40 (80%) patients achieved complete remission. Partial remission was stated in 8/40 (20%) patients who had further 2 cycles of chemotherapy using the R-DHAP program and autologous hematopoietic stem cell transplantation (a BEAM conditioning mode). Two-year overall and relapse-free survival rates were 100% and 96%, respectively; the median follow-up was 17 months. The R-DA-EPOCH regimen allows complete remission in 80% of the cases and two-year survival in 100%. If there are unfavorable factors at onset and in partial remission, it is appropriate to intensify treatment at early stages, by using high-dose chemotherapy and autologous hematopoietic stem transplantation.

Non-Hodgkin’s Lymphomas in Children: 25-Year Clinical Experience

Background &amp; Aims. Current polychemotherapeutic protocols based on differentiated and risk-adopted approaches permitted to consider non-Hodgkin's lymphomas (NHL) potentially curable diseases although they had been considered fatal previously. The aim of this study is to summarize and analyze outcomes of NHL therapy over a 25-year period. Methods. 246 patients were enrolled in the study. They were treated in the department of chemotherapy of hemoblastoses in the Scientific Research Institute of Pediatric Oncology and Hematology under the NN Blokhin Russian Cancer Research Center over the period of 25 years: from April 1, 1991, till June 1, 2016. B-NHL-BFM 90/95 protocols and a modified B-NHL-BFM 95 protocol (with rituximab) were used for B-cell NHLs (n = 130). Patients with lymphocytic leukemia (n = 75) were treated using ALL-mBFM 90/95 and ALL IC-BFM 2002 protocols. 21 patients with anaplastic large cell lymphomas (ALCL) received treatment according to the B-NHL-BFM 90/95 protocol, and 20 patients received the НИИ ДОГ-АККЛ-2007 protocol. Results. Taking into account clinical and immunological characteristics of ALCL, the authors invented an original НИИ Д0Г-АККЛ-2007 protocol. Special attention was paid to potential modification of standard treatment regimens for B-cell NHL by adding rituximab. The article demonstrates the evolution in prescription of rituximab for B-cell NHL and possibilities for reduction of the total number of polychemotherapy cycles for late-stage tumors without deterioration of treatment outcomes. Conclusion. The obtained results permit to conclude that introduction of achievements of oncoimmunology, molecular biology, and cytogenetics will become the basis for further modification of existing treatment options for NHL.

Isolated primary central nervous system lymphoma arising from the optic chiasm

A 58-year-old previously healthy woman rapidly developed progressive bilateral visual loss. Magnetic resonance imaging revealed a bulging appearance of the optic chiasm, with homogeneous enhancement after gadolinium administration, which suggested an optic glioma or inflammatory disease. In the absence of (para)clinical clues for a specific diagnosis despite extensive investigation, a biopsy of one optic nerve was performed, resulting in a diagnosis of non-Hodgkin B-cell lymphoma. There was no evidence of any other ocular or systemic involvement, therefore the conclusion was that this immunocompetent patient had a primary central nervous system lymphoma isolated in the anterior visual pathway. Treatment included two cycles of polychemotherapy (rituximab, methotrexate, carmustine, etoposide, methylprednisolone), followed by autologous peripheral blood stem cell transplantation and rituximab plus cytarabine consolidation therapy. Subsequently, the patient exhibited significant improvement in vision, and was still disease-free at the 1-year follow-up examination. The aim of the present paper was to provide well-documented clinical, radiological, and intraoperative features of isolated primary malignant lymphoma arising from the anterior visual pathway. A better recognition of this rare pathological entity is necessary for clinicians who may encounter similar presentations, as prompt management is crucial for both a visual and vital prognosis.

FDG PET/CT Appearance of Portal Vein Tumor Thrombus in the Gastric Primitive Neuroectodermal Tumor

Gastric primitive neuroectodermal tumor (PNET) is a very rare tumor. There are only a few case reports in the literature. Although cases with FDG uptake in the portal venous tumor thrombus (PVTT) in different primary malignancies have been evaluated before, the coexistence of PNET and PVTT has not been reported yet. Herein, we report the case of a gastric PNET with PVTT, which resolved after 3 cycles of polychemotherapy except for a residual tumor focus in the gastric corpus.

Optimal postoperative radiotherapy treatment of orbital rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common sarcoma of the soft tissue, mostly affecting the region of head and neck (orbit, paranasal sinus). Histological types include embryonal (66-70%) with better prognosis, and alveolar type (20%) with poorer prognosis. There are also diffuse anaplastic and undifferentiated sarcomas (10%). Due to multimodal therapy approach (surgery, chemotherapy and radiotherapy), RMS survival rate is considerably improving. Nevertheless, early diagnosis of RMS is of crucial importance for the outcome of treatment. Standard conformal radiation therapy is very complex due to closeness of many critical structures of head and neck, thus limiting optimal tumor dose coverage. Patient aged 59 years, surgically treated for RMS of nasal cavity several times before radiation therapy treatment. Due to relapse, patient was re-operated, when subtotal re-resection of the maxilla with exenteration of the right orbit was done. The patient received IV cycles of polychemotherapy postoperatively. Standard procedure and planning for conformal radiation therapy did not lead to acceptable irradiation plan, and hence modification in the patient's preparation was done, resulting in optimal therapeutic plan according to internationally recognized recommendations. The reported case shows a rare pediatric tumor, which often occurs in children but extremely rare in adults. The problem of inadequate isodose distribution obtained by standard conformal plan was solved by placing bolus material into the orbital cavity.The outcome of the treatment plan showed much better isodose distribution and tumor bed coverage.

Primary Ewing's sarcoma of vulva: A case report and a review of the literature

Ewing sarcomas/peripheral primitive neuroectodermal tumors (ES/pPNET) are extremely rare in the vulva. A review of the literature reveals only 14 previously reported possible cases. Here we reported a case of primary extraskeletal Ewing's sarcoma (EES) of the vulva in a 37-year-old woman. Characteristic histologic features of ES/pPNET were present in this case, including a monomorphic population of small round blue cells with cytoplasmic glycogen confirmed by periodic acid-Schiff, membrane staining with CD99 and nuclear staining with FLI-1. After surgery, the patient was found to have pulmonary metastasis and then received six cycles of polychemotherapy. She is still alive with stable disease after 1 year of follow up. Our findings underline the crucial role of immunohistochemical techniques in the differential diagnosis of small round cell tumors in these unusual locations. We also give a summary about the clinical and pathological features of the primary ES/pPNET in the vulva reported previously in the literature.

Early complete response during chemotherapy predicts favorable outcome in patients with primary CNS lymphoma

In primary central nervous system lymphoma (PCNSL), 2 international prognostic scores have been developed to estimate the outcome according to certain "prognostic groups". However, these scores do not predict the individual course of a single patient under therapy. In this analysis, we addressed the question of whether early tumor remission in patients still under therapy, according to magnetic resonance imaging (MRI) criteria, helps to predict long-term outcome. Eighty-eight patients treated with 6 polychemotherapy cycles within a pilot/phase II trial underwent MRI scanning within 72 hours prior to initiation of therapy, after the second chemotherapy cycle, and after completion of chemotherapy. Response was assessed by contrast-enhanced MRI of the brain according to the Macdonald criteria. Median follow-up was 42 months (range, 0-124 months). Patients achieving a complete radiographic response after 2 courses of chemotherapy (n = 18) had a significantly longer median overall survival (OS) (not reached) and median time-to-treatment failure (TTF) (not reached) than patients with complete response (CR) after termination of treatment but with only a partial response after the second cycle (n = 24) (OS: 55 months; TTF: 32 months) (P < .01). Early complete tumor response assessed by MRI after the second of sixth scheduled chemotherapy cycles was highly predictive for both OS and TTF in patients with PCNSL treated in this series.

Gene Expression Profiling of Microdissected Hodgkin Reed Sternberg Cells: Molecular Subtypes and Treatment Outcome Correlations.

Abstract 268 INTRODUCTION:Classical Hodgkin lymphoma (cHL) is unique among lymphomas due to the scarcity of the malignant Hodgkin Reed Sternberg (HRS) cells, which are derived from clonal germinal center B cells. Investigations using laser capture microdissection permit more detailed analysis of these cells. However, most recent studies were limited by low case numbers and lack of available clinical data. PATIENTS AND METHODS:We studied 29 cases of cHL and the 5 HL lines KMH2, HDLM2, L428, L540, and L1236 by gene expression profiling. All patients were treated at the BC Cancer Agency between 1984 and 2006 and received at least 4 cycles of polychemotherapy and stage-dependent radiotherapy. The cohort also included 5 biopsies taken at relapse. Treatment failure was defined as disease progression or relapse at any time (n=14) after initiation of treatment; treatment success as absence of progression (n=15). We used laser microdissection (Molecular Machines & Industries Cellcut with Nikon Eclipse TE2000-S microscope) to study the enriched HRS cell compartment separately from the microenvironment. RNA extraction was performed on pools of 1000 microdissected HRS cells in each case. Gene expression profiles were generated using Affymetrix HG UA133 2.0 Plus arrays using two-cycle labeling reactions. HRS cell profiles were compared to microdissected germinal centers (GC), and HL cell line profiles compared to enriched tonsillar CD77+ centroblasts (MACS cell separation, Miltenyi). Furthermore, we compared gene expression profiles of treatment failures to those of treatment successes. RESULTS:We identified 1342 differentially expressed probesets (fold change >5, False Discovery Rate (FDR) adjusted p value <0.001) between HRS and GC cells. Using overrepresentation analysis we found genes involved in NFκB, JAK/Stat, IL-6, IL-9 signaling, cytotoxic T lymphocyte-mediated apoptosis and IL-15 production to be significantly over-expressed in HRS cells and genes involved in B cell, T cell receptor signaling and many transcriptional regulators such as FOXO1, E2F5, IRF8, NFATC1, NFYB, POU2AF1 to be significantly under-expressed in HRS cell. Comparison of these data to differentially expressed genes in the HL cell lines (1004 genes, fold change >5, FDR-adjusted p value <0.001) showed significant overlap of genes involved in proliferation, apoptosis, IL15 signaling and B cell receptor signaling, while overrepresentation of metabolism genes was unique to the cell lines. Hierarchical clustering of all 29 primary HL cases identified 3 separate clusters characterized by 1) a cytotoxic signature, 2) TNF/TGFB receptor signaling or 3) a residual B cell signature. Dichotomizing the profiles into the two treatment outcome groups demonstrated that NFγB signaling, complement system genes and genes involved in the developmental process of hematopoietic progenitor cells, macrophages and blood vessels were overexpressed in treatment failure samples. DISCUSSION:Using microdissection of HRS cells in a large number of cases we were able to further characterize the unique expression program of HL and refine the data inventory about dysregulated cellular functions and pathways in this disease. Overexpression of genes associated with NFκB, complement and hematopoietic progenitor cells proliferation correlate strongly with treatment failure. Further study using immunohistochemistry is currently ongoing to validate these findings and to develop clinically useful biomarkers. Disclosures:Gascoyne:Roche Canada: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.