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The issues discussed in this paper provide for further development of studies in the sphere of imaging spectroscopy and laser vision. In terms of forming the information fields (radiation fields), the electro-optical systems are subdivided into the passive and active ones. Passive electro-optical systems use the information fields formed by natural radiation sources, whereas the active ones suggest using artificial sources. Comparative analysis of mathematical and physical issues of designing the electro-optical systems with dynamic spectral processing of optical radiation of the passive and active types has been performed. It has been shown that the controlled dynamic spectral processing of optical radiation can be implemented within the passive and active electro-optical systems on the basis of the same algorithm that represents operation of the optical processor performing the mathematical operation of dot product. The authors have developed the block diagram of an active electro-optical system with dynamic spectral processing. The algorithm for optimal detection of optical signals has been developed using basics of the signal detection theory. Mathematical modeling of target detection against an inhomogeneous background has been performed. It has been shown that the optimal dynamic spectral processing of optical radiation in active electro-optical system enables to separate the desired optical signal by suppressing the background signal.

The article is devoted to the study of the properties of the electro-optical systems with matched spectral dynamic filtration. It is usually supposed that the optimal optical signal detector is synthesized under the assumption of a priori information about the statistical characteristics of the target and background signals and the equality of the target and the background correlation matrices. However, in practice, there is always a mismatch between the input and the reference (expected) optical signals. The purpose of this article is to generalize and develop the methods for estimation of matching of the optimal signal processing in electro-optical systems with dynamic spectral filtration, which makes it possible to study the effect of the difference between the input and reference signals on the processing quality. In this paper, the information criterion – the normalized Kullbak–Leibler divergence, which is the ratio of the divergences at the output and input of the dynamic spectral filter – is used as a measure of matching of the optimal signal processing in electro-optical systems with dynamic spectral filtration. The analysis of the properties of the suggested information matching indicator and its comparison with the probability of correct detection is carried out. A mathematical model of the process of optimal dynamic spectral filtration in electro-optical systems is constructed. The examples show the extent to which the differences in the statistical characteristics of input and reference signals affect the information matching indicator. In particular, the article poses and solves three problems that illustrate the process of optimal spectral filtration in the following situations: 1) the statistical properties of the input and the reference signals coincide completely; 2) the mean brightness of the optical radiation of the target and the background at the input of the electro-optical system has changed; 3) the statistical characteristics of the background input signal differ from the reference values.

This paper generalizes and develops the principles of dynamic spectral filtration, which is a further development of imaging spectroscopy. Electro-optical systems with dynamic spectral filtration in contrast to imaging spectrometers realize controlled spectral filtration, which ensures maximum suppression of the spectral components of background radiation with a minimum attenuation of the target optical signal in the pre-detector area. The purpose of the article is to generalize and develop the principles of dynamic spectral filtration in the interests of creating electro-optical systems of targets detection by spectral features. The problem of optimal selection of optical signals from background noise has been reduced to solving a problem of signal detection with a priori known parameters used in radiolocation theory. The article states the principles of dynamic spectral filtration of optical radiation. It also describes an algorithm for optimal detection of targets by spectral characteristics and carries out a synthesis of an optimal optical signal detector. The paper defines the quantitative characteristics of the detector, that for a given false alarm level allows to determine the conditional probability of correct detection of the targets of observation depending on the signal-to-interference ratio. The quantitative characteristics of the detector were obtained on the assumption that the signals of the target and the background obey the normal distribution law, and their correlation characteristics (the correlation matrices of the background and the target) are equal. The work experimentally establishes the possibility of creating a controlled acoustooptic selection device providing a spectral selection of two optical signals differing in spectral composition by varying the amplitude of the frequency components of an ultrasonic wave. In this case, three lasers operating in the red, green and blue regions of the spectrum were used as the source of optical radiation. In the course of the experiment, spectral selection was provided by diffraction of polychromatic laser radiation by multifrequency ultrasound. The efficiency of the filtration process was determined by the contrast value before and after filtration. It was experimentally established that, in the presence of three spectral channels of selection, it is possible to increase the contrast at the output in several times.

The paper is devoted to the principles of constructing active electro-optical systems with dynamic spectral processing of optical radiation in order to enhance the contrast of search objects images. In active electro-optical systems with dynamic processing the spectral composition of the polychromatic probing radiation is formed using laser signals based on a priori information about the spectral characteristics of the object and the background. The spectrum of the probing radiation is formed in such a way that at the output of the electro-optical system a minimum response is formed for the radiation reflected from the background and the maximum response of the radiation reflected from the object's surface. A block diagram of the active electro-optical systems and results of mathematical modeling of the signal processing in it are given.

Background Although chemotherapy has improved outcome of osteosarcoma, 30–40% of patients succumb to this disease. Survivors experience substantial morbidity and mortality from anthracycline-induced cardiotoxicity. We hypothesized that the cardioprotectant dexrazoxane would 1) support escalation of the cumulative doxorubicin dose (600 mg/m2) and 2) not interfere with the cytotoxicity of chemotherapy measured by necrosis grading in comparison to historical control data.9

This manuscript describes the experience from registration until randomisation for a cohort of 2260 patients with osteosarcoma who joined the EURAMOS-1 trial. This includes pre-operative chemotherapy and surgery. It sets out the practical issues in collaboration and in achieving randomisation., Background Four international study groups undertook a large study in resectable osteosarcoma, which included two randomised controlled trials, to determine the effect on survival of changing post-operative chemotherapy based on histological response. Patients and methods Patients with resectable osteosarcoma aged ≤40 years were treated with the MAP regimen, comprising pre-operatively of two 5-week cycles of cisplatin 120 mg/m2, doxorubicin 75 mg/m2, methotrexate 12 g/m2 × 2 (MAP) and post-operatively two further cycles of MAP and two cycles of just MA. Patients were randomised after surgery. Those with ≥10% viable tumour in the resected specimen received MAP or MAP with ifosfamide and etoposide. Those with

To investigate the role of insulin-like growth factor-1 (IGF-1), in localized osteosarcoma, serum levels of IGF-1, IGFBP-2, and IGFBP-3 were measured in 224 similarly treated, newly diagnosed patients. We demonstrated that younger patients had lower concentrations of IGF-1 and IGFBP-3 compared to older (P

The paper describes the results of experimental research of dynamic spectral filtration using polychromatic laser radiation interaction with multi-frequency acoustic wave. Optical radiation sources were three semiconductor lasers operating in the bands of red, green and blue portions of the spectrum and absorption filters — elements simulating the spectral properties of the reflective surfaces of the target and the background. Instrument function of managed spectral selection device was formed in such a way as to ensure the suppression of spectral components of the background radiation with minimal attenuation of the optical signal of the target

Purpose Despite efforts to intensify chemotherapy, survival for patients with metastatic osteosarcoma remains poor. Overexpression of human epidermal growth factor receptor 2 (HER2) in osteosarcoma has been shown to predict poor therapeutic response and decreased survival. This study tests the safety and feasibility of delivering biologically targeted therapy by combining trastuzumab with standard chemotherapy in patients with metastatic osteosarcoma and HER2 overexpression. Patients and Methods Among 96 evaluable patients with newly diagnosed metastatic osteosarcoma, 41 had tumors that were HER2-positive by immunohistochemistry. All patients received chemotherapy with cisplatin, doxorubicin, methotrexate, ifosfamide, and etoposide. Dexrazoxane was administered with doxorubicin to minimize the risk of cardiotoxicity from treatment with trastuzumab and anthracycline. Only patients with HER2 overexpression received concurrent therapy with trastuzumab given for 34 consecutive weeks. Results The 30-month event-free and overall survival rates for patients with HER2 overexpression treated with chemotherapy and trastuzumab were 32% and 59%, respectively. For patients without HER2 overexpression, treated with chemotherapy alone, the 30-month event-free and overall survival rates were 32% and 50%, respectively. There was no clinically significant short-term cardiotoxicity in patients treated with trastuzumab and doxorubicin. Conclusion Despite intensive chemotherapy plus trastuzumab for patients with HER2-positive disease, the outcome for all patients was poor, with no significant difference between the HER2-positive and HER2-negative groups. Although our findings suggest that trastuzumab can be safely delivered in combination with anthracycline-based chemotherapy and dexrazoxane, its therapeutic benefit remains uncertain. Definitive assessment of trastuzumab's potential role in treating osteosarcoma would require a randomized study of patients with HER2-positive disease.

Purpose: Osteosarcoma most commonly recurs in the lung. Based on preliminary data on the antitumor effects of granulocyte-macrophage colony stimulating factor (GM-CSF) in animal models, and promising phase I trials, we embarked on a feasibility study of inhaled GM-CSF in patients with first isolated pulmonary recurrence of osteosarcoma. Experimental Design: Forty-three eligible patients received inhaled GM-CSF at doses from 250 to 1,750 μg twice daily on alternate weeks. Following two cycles, patients underwent thoracotomy to resect tumor and analyze pulmonary nodules for expression of Fas/Fas ligand (Fas/FasL), and the presence of dendritic cells by immunostaining for CD1a, clusterin, and S100. Following surgery, patients received 12 additional cycles of therapy on alternating weeks or until progression. Event-free survival and survival, and feasibility of therapy delivery were evaluated. Results: Dose escalation to 1,750 μg twice daily was feasible with no dose-limiting toxicity. Mean scores for Fas/FasL in nodules from patients with bilateral recurrence who underwent unilateral thoracotomy pretreatment (using a scoring system of 0-3) were 1.3 and 0.88, respectively, compared with 0.78 and 0.62 in nodules resected following two cycles of therapy. Only 11 of 30 nodules postinhalation were positive for CD1a, 4 of 30 for S100, and 6 of 30 for clusterin. Event-free and overall survival at 3 years were 7.8% and 35.4%, respectively. Conclusions: Inhalation of GM-CSF at doses from 250 to 1,750 μg twice daily on alternate weeks was feasible with low toxicity. However, no detectable immunostimulatory effect in pulmonary metastases or improved outcome postrelapse was seen. Clin Cancer Res; 16(15); 4024–30. ©2010 AACR.

Trait self-enhancement has been consistently associated with genuine adaptive benefits, as well as some social liabilities. In the current investigation, we examined whether self-enhancement might generate social benefits. Among a sample of high-exposure survivors of the September 11th terrorist attack (Study 1), trait self-enhancement was associated with leadership behaviors during the 9/11 attack, with a larger social network, and with greater daily contact with close friends/relatives. The association between self-enhancement and social network size was replicated in a college sample (Study 2), even when social desirability was statistically controlled. A previous finding (Bonanno, Rennicke, & Dekel, 2005) linking self-enhancement with reduced social constraints against personal disclosure was also replicated in Study 2. However, when compared with actual social constraints reported by participants' friends/relatives, self-enhancers' perceptions appeared to be illusory. Together, these findings suggest...

Purpose Multiple drug resistance due to P-glycoprotein (P-gp) expression has been reported to be a cause of disease recurrence in osteosarcoma. Tumor specimens derived from children and young adults with osteosarcoma enrolled onto a national Intergroup trial (INT0133) were analyzed prospectively to determine the role of multiple drug resistance in osteosarcoma. Patients and Methods From October 15, 1992, to November 25, 1997, 685 patients with localized, high-grade osteosarcoma were enrolled onto INT0133. Paraffin-embedded diagnostic tumor specimens were assayed for P-gp using monoclonal antibodies C-494 (139 patients) and JSB-1 (133 patients). Percent necrosis at the time of definitive surgery (NEC), event-free survival (EFS), and overall survival (OS) were evaluated as outcome measures for patients with P-gp–positive disease and were compared with patients with P-gp–negative disease. Results P-gp expression in the biopsy specimen did not significantly increase the risk for adverse outcomes as measured by EFS, OS, or NEC. EFS for those patients with C-494–positive tumors was 59% at 4 years versus 61% at 4 years for patients with C-494–negative tumors (P = .79), or 58% at 4 years versus 61% at 4 years for patients with JSB-1–positive versus JSB-1–negative tumors (P = .65). OS for patients with C-494–positive tumors was 82% at 4 years versus 82% at 4 years for patients with C-494–negative tumors (P = .61). Conclusion Prospective analysis of the role of multiple drug resistance in localized osteosarcoma did not find that immunohistochemical analysis of P-gp expression predicted outcome for patients treated on INT0133.

PurposeEURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-α-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy.Patients and methodsAt diagnosis, patients age ≤ 40 years with resectable high-grade osteosarcoma were registered. Eligibility after surgery for good response random assignment included ≥ two cycles of preoperative MAP (methotrexate, doxorubicin, and cisplatin), macroscopically complete surgery of primary tumor, < 10% viable tumor, and no disease progression. These patients were randomly assigned to four additional cycles MAP with or without IFN-α-2b (0.5 to 1.0 μg/kg per week subcutaneously, after chemotherapy until 2 years postregistration). Outcome measures were event-free survival (EFS; primary) and overall survival and toxicity (secondary).ResultsGood response was reported in 1,041 of 2,260 registered patients; 716 consented to random assignment (MAP, n = 359; MAP plus IFN-α-2b, n = 357), with baseline characteristics balanced by arm. A total of 271 of 357 started IFN-α-2b; 105 stopped early, and 38 continued to receive treatment at data freeze. Refusal and toxicity were the main reasons for never starting IFN-α-2b and for stopping prematurely, respectively. Median IFN-α-2b duration, if started, was 67 weeks. A total of 133 of 268 patients who started IFN-α-2b and provided toxicity information reported grade ≥ 3 toxicity during IFN-α-2b treatment. With median follow-up of 44 months, 3-year EFS for all 716 randomly assigned patients was 76% (95% CI, 72% to 79%); 174 EFS events were reported (MAP, n = 93; MAP plus IFN-α-2b, n = 81). Hazard ratio was 0.83 (95% CI, 0.61 to 1.12; P = .214) from an adjusted Cox model.ConclusionAt the preplanned analysis time, MAP plus IFN-α-2b was not statistically different from MAP alone. A considerable proportion of patients never started IFN-α-2b or stopped prematurely. Long-term follow-up for events and survival continues.

BackgroundFour international study groups undertook a large study in resectable osteosarcoma, which included two randomised controlled trials, to determine the effect on survival of changing post-operative chemotherapy based on histological response.Patients and methodsPatients with resectable osteosarcoma aged ≤40 years were treated with the MAP regimen, comprising pre-operatively of two 5-week cycles of cisplatin 120 mg/m(2), doxorubicin 75 mg/m(2), methotrexate 12 g/m(2) × 2 (MAP) and post-operatively two further cycles of MAP and two cycles of just MA. Patients were randomised after surgery. Those with ≥10% viable tumour in the resected specimen received MAP or MAP with ifosfamide and etoposide. Those with

Although chemotherapy has improved outcome of osteosarcoma, 30-40% of patients succumb to this disease. Survivors experience substantial morbidity and mortality from anthracycline-induced cardiotoxicity. We hypothesized that the cardioprotectant dexrazoxane would (i) support escalation of the cumulative doxorubicin dose (600 mg/m(2)) and (ii) not interfere with the cytotoxicity of chemotherapy measured by necrosis grading in comparison to historical control data.Children and adolescents with nonmetastatic osteosarcoma were treated with MAP (methotrexate, doxorubicin, cisplatin) or MAPI (MAP/ifosfamide). Dexrazoxane was administered with all doxorubicin doses. Cardioprotection was assessed by measuring left ventricular fractional shortening. Interference with chemotherapy-induced cytotoxicity was determined by measuring tumor necrosis after induction chemotherapy. Feasibility of intensifying therapy with either high cumulative-dose doxorubicin or high-dose ifosfamide/etoposide was evaluated for "standard responders" (SR,98% tumor necrosis at definitive surgery).Dexrazoxane did not compromise response to induction chemotherapy. With doxorubicin (450-600 mg/m(2)) and dexrazoxane, grade 1 or 2 left ventricular dysfunction occurred in five patients; 4/5 had transient effects. Left ventricular fractional shortening z-scores (FSZ) showed minimal reductions (0.0170 ± 0.009/week) over 78 weeks. Two patients (1%) had secondary leukemia, one as a first event, a similar rate to what has been observed in prior trials. Intensification with high-dose ifosfamide/etoposide was also feasible.Dexrazoxane cardioprotection was safely administered. It did not impair tumor response or increase the risk of secondary malignancy. Dexrazoxane allowed for therapeutic intensification increasing the cumulative doxorubicin dose in SR to induction chemotherapy. These findings support the use of dexrazoxane in children and adolescents with osteosarcoma.

Purpose To determine whether the addition of ifosfamide and/or muramyl tripeptide (MTP) encapsulated in liposomes to cisplatin, doxorubicin, and high-dose methotrexate (HDMTX) could improve the probability for event-free survival (EFS) in newly diagnosed patients with osteosarcoma (OS). Patients and Methods Six hundred seventy-seven patients with OS without clinically detectable metastatic disease were treated with one of four prospectively randomized treatments. All patients received identical cumulative doses of cisplatin, doxorubicin, and HDMTX and underwent definitive surgical resection of the primary tumor. Patients were randomly assigned to receive or not to receive ifosfamide and/or MTP in a 2 × 2 factorial design. The primary end point for analysis was EFS. Results Patients treated with the standard arm of therapy had a 3-year EFS of 71%. We could not analyze the results by factorial design because we observed an interaction between the addition of ifosfamide and the addition of MTP. The addition of MTP to standard chemotherapy achieved a 3-year EFS rate of 68%. The addition of ifosfamide to standard chemotherapy achieved a 3-year EFS rate of 61%. The addition of both ifosfamide and MTP resulted in a 3-year EFS rate of 78%. Conclusion The addition of ifosfamide in this dose schedule to standard chemotherapy did not enhance EFS. The addition of MTP to chemotherapy might improve EFS, but additional clinical and laboratory investigation will be necessary to explain the interaction between ifosfamide and MTP.

BACKGROUND Recurrent osteosarcoma is a drug-resistant disease with a dismal prognosis. The objective of this Phase II study was to evaluate the activity of ecteinascidin 743 (ET-743) as a salvage therapy in these patients. METHODS Patients with recurrent osteosarcoma who had received standard chemotherapeutic agents were eligible. ET-743 was administered at a dose of 1500 μg/m2 as a 24-hour infusion every 3 weeks. Pharmacokinetic studies were performed during the first cycle. RESULTS Twenty-five patients were enrolled, 23 of whom were assessable for response (median age of 18 years; range, 12–67 years). The median number of previous chemotherapeutic agents was five (range, three to eight previous agents). Sixty-one cycles were administered (median number of cycles per patient was 2; range, 1–9 cycles per patient). Three patients (12%) achieved minor responses (49% 36% and 25%, respectively). Fifteen patients (60%) developed a transient elevation of hepatic transaminases (Grade 3 or 4 [according to the National Cancer Institute Common Toxicity Criteria]), which was not cumulative. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 12 patients (48%) and 6 patients (24%), respectively. The mean area under the curve (AUC) in 4 patients experiencing Grade 4 toxicity (76.4 ± 29.3 ng × hr/mL) was significantly greater (P = 0.034) than that in those for whom the most severe toxicity was Grade 3 (39.5 ± 17.2 ng × hr/mL [n = 12]) or Grade 1-2 (52.6 ± 15.6 ng × hr/mL [n = 5]). There were no other significant correlations found between pharmacokinetic variables and patient characteristics, toxicity, or therapeutic response. CONCLUSIONS ET-743 was found to be well tolerated in heavily pretreated osteosarcoma patients but had limited antitumor activity as a single agent. The combination of ET-743 with cisplatin or doxorubicin should be considered. Cancer 2003;98:832–40. © 2003 American Cancer Society. DOI 10.1002/cncr.11563

Purpose: Successful therapeutic interventions to prevent disease progression in patients with nonmetastatic osteosarcoma have included surgery with adjuvant chemotherapy. Presurgical chemotherapy has been advocated for these patients because of putative improvement in event-free survival (EFS). The advantages of presurgical chemotherapy include early administration of systemic chemotherapy, shrinkage of primary tumor, and pathologic identification of risk groups. The theoretic disadvantage is that it exposes a large tumor burden to marginally effective chemotherapy. The contribution of chemotherapy and surgery timing has not been tested rigorously. Patients and Methods: Between 1986 and 1993, we conducted a prospective trial in patients with nonmetastatic osteosarcoma who were assigned randomly to immediate surgery or presurgical chemotherapy. Except for the timing of surgery (week 0 or 10), patients received 44 weeks of identical combination chemotherapy that included high-dose methotrexate with leucovorin rescue, doxorubicin, cisplatin, bleomycin, cyclophosphamide, and dactinomycin. Results: One hundred six patients were enrolled onto this study. Six were excluded from analysis. Of the remaining 100 patients, 45 were randomly assigned to immediate chemotherapy, and 55 were randomly assigned to immediate surgery. Sixty-seven patients remain disease-free. At 5 years, the projected EFS ± SE is 65% ± 6% (69% ± 8% for immediate surgery and 61% ± 8% for presurgical chemotherapy; P = .8). The treatment arms had similar incidence of limb salvage (55% for immediate surgery and 50% for presurgical chemotherapy). Conclusion: Chemotherapy was effective in both treatment groups. There was no advantage in EFS for patients given presurgical chemotherapy.

PURPOSE: The objectives of this trial were to estimate the response rate, progression-free survival, and overall survival of patients who received therapy with etoposide and high-dose ifosfamide, and to define the toxicity of this combination when provided with standard chemotherapy in patients with newly diagnosed metastatic osteosarcoma. PATIENTS AND METHODS: Eligible patients received infusions of 100 mg/m2 per day of etoposide and 3.5 g/m2 per day of ifosfamide for 5 days. Therapy with granulocyte colony-stimulating factor was begun on day 6. This was repeated 3 weeks after therapy was begun. Response was determined at week 6 by both standard World Health Organization response criteria and by pathologic determination of tumor necrosis of the primary tumor. RESULTS: Forty-three patients were registered; 39 were assessable for response and 41 for toxicity and survival. Twenty-eight (68%) of 41 had metastatic sites only in the lung; 12 (29%) had metastatic sites in other bones with or without lung involvement. Four patients (10%) experienced complete response, and 19 patients (49%) experienced partial response, for an overall response rate of 59% ± 8%. The projected 2-year progression-free survival (PFS) for the 28 patients with metastases to lungs was 39% ± 11%. The projected 2-year PFS for the 12 patients with metastases to other bones (with or without pulmonary metastases) was 58% ± 17%. Two patients died as a result of therapy toxicity. Eighty-three percent of patients had grade 4 neutropenia, and 29% had grade 4 thrombocytopenia. Ten patients (24%) had sepsis. Fanconi’s syndrome was observed in five patients. CONCLUSION: The combination of etoposide and high-dose ifosfamide is effective induction chemotherapy for patients with metastatic osteosarcoma, despite significant associated myelosuppression sometimes complicated by infection and renal toxicity.

A comprehensive multidisciplinary approach has transformed osteosarcoma from a disease with a modest long-term survival to one in which at least two-thirds of patients will be cured. Surgery remains the vital modality for treating the primary tumor, whereas adjuvant chemotherapy plays an essential role in the control of subclinical metastatic disease. Complete surgical excision of the primary tumor remains an essential element of treatment. For many patients, a combination of advances in surgical technique, improved imaging modalities to accurately document tumor extent, and the effect of neoadjuvant chemotherapy has made limb salvage procedures a safe alternative to amputation. In some patients for whom complete surgical excision is impossible, the addition of radiation therapy may allow local tumor control. The most effective chemotherapy agents currently in use include high-dose methotrexate, doxorubicin, cisplatin, and ifosfamide/etoposide. The optimal schedule of therapy is still being investigated, as is the role of dose intensification. Unfortunately, some groups of patients remain at high risk of eventual relapse. Those whose tumors show relatively low degrees of necrosis after administration of chemotherapy have poorer survival than patients with more chemotherapy-responsive tumors. Similarly, patients who present with overt metastatic disease (particularly bone metastases), as well as patients with tumors that recur after treatment, continue to have an unsatisfactory outcome. These groups, in particular, may benefit from future investigations into novel agents, such as biological response modifiers, antiangiogenesis factors, and growth receptor modulation.