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"Abstract Purpose: High linear energy transfer particles are shown to reduce tumor radiation resistance originating from hypoxia. " Hence, we investigated the clinical implications of high LET carbon beam therapy on cervical cancer. This review involved 49 patients with stage IIIb bulky and stage IVa cervical cancer treated with high LET carbon beams between October 1995 and June 2000. Hg and pO2 > 20 mm Hg before treatment had respectively increased by 47% and 21%, respectively, with pO2 u2264 20 mm Hg and pO2 > 20 mm Hg before treatment. Conclusion: The similar disease-free survival and local control rates between hypoxic and oxygenated tumors before and during therapy demonstrated that the role of the tumor oxygenation status was not relevant in local control of carbon beam therapy. These findings indicated that elevated LET carbon beam irradiation could reduce the radiation-resistant nature of tumor hypoxia. ".
Source link: https://doi.org/10.1158/1078-0432.ccr-05-1907
"Abstract PURPOSE: Raf proteins are key components of cell signaling pathways and play a role in cancer cell resistance to radiation therapy. " Antisense oligonucleotides to c-raf-1 inhibit highly selective inhibition of the gene product and provide a method for sensitizing cancer cells to radiation therapy. We reviewed the safety of combined liposomal formulations of raf antisense oligonucleotide and radiation therapy in patients with advanced malignancies in this dose escalation study. XPERIMENTAL DESIGN: Patients with advanced solid tumors were treated with LErafAON in a phase I dose escalation trial when doing palliative radiation therapy. In peripheral blood mononuclear cells, pharmacokinetics and expression of c-raf-1 mRNA and Raf-1 protein were determined. RESULTS: This study included seventeen patients with palliative symptoms for radiation therapy. Thirteen patients received LerafAON daily infusions, and four more were given twice-weekly infusions. Twelve of the seventeen patients were evaluable for tumor response at the end of therapy; four of them had partial response, four showed stable disease, and four others had progressive disease. Six patients with partial or chronic disease were evaluable for c-raf-1 mRNA and/or Raf-1 protein expression, and/or Raf-1 protein expression. In three of five patients, c-raf-1 mRNA inhibition was observed. In four of five patients, Raf-1 protein was blocked. This is the first report of the combined modality therapy of patients with advanced cancer using antisense oligonucleotides with radiation therapy. With premedication, a dose of 2. 0 mg/kg of LerafAON is well tolerated and does not raise radiation toxicity in patients. ".
Source link: https://doi.org/10.1158/1078-0432.ccr-05-1260
"We conducted an early-phase review to establish the safety of nelfinavir with hypofractionated radiotherapy, as well as the development of tumor perfusion and radiosensitization for this combinatorial strategy. " During pelvic RT, ten patients with T3-4 N0-2 M1 rectal cancer were given 7 days of oral nelfinavir and another 7 days of nelfinavir. Tumor cell density was determined by chemists pretreatment and 7 days after the last fraction of RT were delayed. On DCE-MRI, there was a mean 42 percent rise in median Ktrans and a corresponding median 30 percent rise in mean blood flow on p-CT during RT, as well as nelfinavir. Overall, 5 of the nine evaluable patients showed acceptable tumor regression on MRI determined by tumor regression grade, according to the authors. This is the first review to analyze nelfinavir in combination with RT without concurrent chemotherapy. ".
Source link: https://doi.org/10.1158/1078-0432.ccr-15-1489
"Experimental Design: To determine immunologic differences between radiotherapy methods that save or irradiate the DLN, we created a preclinical model to compare stereotactic radiotherapy with or without ENI. " Results: Tumor RT was associated with the upregulation of an intratumoral T-cell chemoattractant chemokine signature that resulted in prolific infiltration of antigen-specific CD8+ effector T cells as well as FoxP3+ regulatory T cells. The combination of stereotactic radiotherapy and ICB resulted in long-term survival in a subset of mice and was associated with improved intratumoral density of antigen-specific CD8+ T cells, as well as improved intratumoral density. Although radiotherapy and anti-PD-1 were both effective in initial tumor prevention and recovery, the ability to refuse tumor on rechallenge was partially dependent on the ICB's intervention; although radiotherapy/anti-CTLA4 was superior to radiotherapy/anti-PD-1. When combining stereotactic radiotherapy with immunotherapy, combining stereotactic radiotherapy and immunotherapy should be considered, particularly the immunomodulatory effect of the radiotherapy program.
Source link: https://doi.org/10.1158/1078-0432.ccr-17-3427
"Abstract Objectives: Recent research has shown that cyclooxygenase-2 inhibitors have potent anti-tumor involvement in prostate cancer both in vitro and in vivo. This report examined the effectiveness of the COX-2 inhibitor celecoxib in prostate-specific antigen recurrent prostate cancer after radiation therapy or radical prostatectomy. Methods: Forty patients with biochemical relapse after XRT or radical prostatectomy were treated with celecoxib 400 mg twice per day on a daily basis. The rate of PSA rise before and after celecoxib therapy for each patient was determined by calculating the slope of the log versus time curve and determining the rate of PSA rise before and after celecoxib therapy for each patient. For both of the time points, the rate of PSA rise before and after celecoxib therapy demonstrated significant flattening of log slope slopes compared to pretreatment. Conclusions: COX-2 inhibitors may have an effect on serum PSA levels in patients with biochemical shift after XRT or radical prostatectomy.
Source link: https://doi.org/10.1158/1078-0432.ccr-05-2067
"Abstract Purpose: "Abstract Purpose: The combination of systemic multiagent chemotherapy and tumor irradiation is the gold standard of care for head and neck squamous cell carcinoma. Experimental Design: Multiple HNSCC cell lines with distinct biological characteristics were treated with sublethal doses of cisplatin and 5-fluorouracil for 24 hours and with 10-Gy irradiation. Enhancement CTL activity was observed in three of three tumor cell lines tested, as compared to target cells exposed to either modality separately, as compared to target cells exposed to either modality separately. In addition, the combined therapy program resulted in a 50% decrease in Bcl-2 expression, although single modality therapy had no influence on this antiapoptotic gene expression. Conclusions: These findings show that CTL killing can be enhanced by multiagent chemotherapy and radiation, as well as combination therapy, which may have decreased or sensitized HNSCC to the permain pathway, perhaps by down-regulating Bcl-2 expression. ".
Source link: https://doi.org/10.1158/1078-0432.ccr-05-1761
"Abstract Purpose: To determine patients with newly diagnosed glioblastoma with concurrent temozolomide, to estimate their progression-free and overall survival, and to determine the role of 11C methionine PET imaging in predicting recurrence. " Late CNS grade u2265III toxicity was detected at 78 and 81 Gy. None of the 22 patients receiving 75 or less Gyregesy developed RT necrosis. The uptake of pretreatment MET-PET uptake of twenty-two of 32 patients with pre-treatment MET-PET uptake exceeded that of the contrast-enhanced MRI. Patients whose hospitalization did not include an increased risk of noncentral failure were at an elevated risk of noncentral failure. Patients with GBM can safely receive standard temozolomide in 30 fractions, provided with IMRT," says author.
Source link: https://doi.org/10.1158/1078-0432.ccr-11-2073
"Radiotherapy is known to enhance tumor immunogenicity, but the role and mechanisms of radiotherapy-induced immune responses are uncertain. " Experimental Design: By flow cytometry and next-generation sequencing of the T-cell receptor repertoire, the effects of low-dose fractionated radiotherapy alone and in combination with u03b1PD-1 mAb on the tumor microenvironment were evaluated. T-cell filtration at the irradiated site has been shown by fractionated radiotherapy; however, the TCR landscape remains dominated by polyclonal proliferation of preexisting T-cell clones. In addition, we have found that effective clearance of tumor following combination therapy is dependent on both T cells living in the tumor at the time of radiotherapy and infiltrating T cells. Conclusions: These results show that radiotherapy can improve T-cell trafficking to locally treated tumor sites and increase pre-existing anticancer T-cell responses with the ability to mediate the recovery of out-of-field tumor lesions when administered in combination with u03b1PD-1 mAb therapy.
Source link: https://doi.org/10.1158/1078-0432.ccr-16-1673
"Abstract Purpose: To demonstrate that a mathematical model can be used to quantitatively determine tumor cellular dynamics during a course of radiotherapy and to predict the likelihood of local control as a result of dose and treatment fractions. Experimental Design: We model results for early-stage, localized non-u2013small cell lung cancer by implementing a mechanistic, cellular dynamics-based tumor control strategy that requires a constant local supply of oxygen and glucose. Precise likelihood best-fit results were determined for the following tests: u03b1 [0. 305 Gyu22121; 95% confidence interval; u03b2 ratio, 0. 105. 136], the u03b1/u03b2 ratio, and the oxygen enrichment ratio for intermediately hypoxic cells receiving glucose but not oxygen based on glucose and not oxygen [0. 01u20130. 365]; 95% confidence interval, 0. 120—u20130. 365] Hypoxia is overcome by the sheer force of high doses per fraction, according to the study, whereas lower dose-per-fraction regimens allow for reoxygenation and corresponding sensitization, but delayed treatments are less effective due to proliferation. ".
Source link: https://doi.org/10.1158/1078-0432.ccr-16-3277
"Abstract is the product of local irradiation. "Abstract Local irradiation is widely used in the treatment of primary and metastatic tumors. " The current rationale for the use of IR is based on direct cytotoxicity to cancer cells, but new research has shown that reduction of tumor burden following ablative IR is largely dependent on type I IFN signaling and CD8+ T-cell responses. Both innate and adaptive immune responses are involved in antitumor effects of radiation. Here, we review recent reports indicating that antitumor reactions of radiation are attributed to both innate and adaptive immune responses. "We're focusing on immune mechanisms, from IR-mediated DNA damage to DNA-sensing immune pathways. ".
Source link: https://doi.org/10.1158/1078-0432.ccr-14-3110
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