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Objective: Although the prognosis of posterior reversible encephalopathy syndrome (PRES) is usually favourable and most patients wholly recover, the disorder can result in death in some patients. To date, the data on clinical features and risk factors for death are still lacking; therefore, we aim to investigate the clinical features and long-term prognostic risk factors of PRES in the present study., Methods: The patients with PRES were identified from the First Affiliated Hospital of Zhengzhou University from June 2011 to June 2020. Clinical characteristics, laboratory tests, magnetic resonance imaging examinations, and treatment of all patients were analyzed retrospectively. All patients were followed up by telephone. Finally, the patients were divided into the survival group and death group for prognosis analysis., Results: A total of 92 patients with PRES were included; 84.8% of whom were female, with an average age of 25.4 (5-66) years at the onset of PRES. Epilepsy was the main clinical manifestation (72.8%). The in-hospital mortality rate was 2.17%. The 3-year all-cause survival rate for PRES patients was 86%. In univariate analysis, patients with systemic lupus erythematosus ( P = 0.027) and blood transfusion history within 1 month before onset ( P = 0.027), need for dialysis ( P ≤ 0.001), nephritis ( P = 0.010), stroke ( P = 0.016), and heart failure ( P = 0.016) were associated with death. In multivariate analysis, we found that heart failure (OR = 0.095, 95% CI 0.020 to 0.441) and stroke (OR = 0.033, 95% CI 0.002 to 0.467) were independent risk factors for death in PRES patients, while pregnancy was a protective factor for death in PRES patients (OR = 7.978, 95% CI 1.446 to 44.006)., Conclusions: Our results indicate that PRES could be considered as a sign of a very high-risk patient. We also demonstrated that heart failure and stroke were independent risk factors for death in patients with PRES; moreover, pregnancy was a protective factor., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Hong-Wei Cui et al.)

Purpose/objective: The primary objective is to examine patient self-assessment of breast pain and cosmesis between three-dimensional (3D-CRT) versus intensity-modulated radiotherapy (IMRT). The secondary objective is to evaluate any relationship of treatment planning conformality of both cohorts to patient-assessed pain. Assessments were performed at interim 12, 24, 36, and 48 months with a final 5-year assessment., Materials/methods: In total, 656 patients (3D-CRT n = 328; IMRT n = 328) were randomly assigned to either IMRT or 3D-CRT accelerated partial breast radiotherapy to 38.5 Gy in 10 BID 3.85 Gy fractions., Results: Median follow-up was 3 years. Multivariate analysis showed that pain severity significantly decreased from baseline to the 12-month follow-up visit (<0.001 for both 3D-CRT and IMRT) in each cohort. There was significantly less pain at 2 (p = 0.002) and 3 years (0.045) in the IMRT arm versus the 3D-CRT arm when compared to the baseline pain level. There was no difference in patient-assessed cosmesis at any follow-up point; however, although MD-assessed cosmesis showed no difference from years 1 to 4, there was significantly better cosmesis for 3D-CRT versus IMRT (p = 0.047) at 5 years. There was a significant correlation between a maximum pain score and an increase in the CI 100 (indicating less conformity) in the IMRT cohort (p < 0.01) and in the IMRT subgroup when the CI 100 was ≤0.37 cohort arm (p = 0.01)., Conclusion: In the analysis of our primary objective we found that at 2 years, IMRT resulted in more interval improvement in breast pain after baseline when compared to patients treated with 3D-CRT planning. As seen in our secondary analysis, this may be due to the ability of IMRT to achieve higher conformality (as evidenced by lower CI values) resulting in less fibrosis. There were no differences in patient-assessed cosmesis or MD-assessed cosmesis for years 1-4; however, physician-assessed 5-year cosmesis was better with 3D-CRT., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: To compare ipsilateral breast event (IBE) risks in patients with ductal carcinoma in situ of the breast (DCIS) post-lumpectomy, as estimated by breast radiation oncologists, the Van Nuys Prognostic Index, the Memorial Sloan Kettering Cancer Center (MSKCC) DCIS nomogram, and the 12-gene Oncotype DX DCIS score assay., Methods and Materials: Consecutive DCIS cases treated with lumpectomy from November 2011 to August 2014 with available DCIS score results were identified. Three radiation oncologists independently estimated the 10-year IBE risk. The Van Nuys Prognostic Index and MSKCC nomogram 10-year IBE risk estimates were generated. Differences and correlations between the IBE estimates and clinicopathologic factors were evaluated., Results: Ninety-one patients were identified for inclusion. Forty-eight percent would have been ineligible for the E5194 study. The mean risk of IBE from the DCIS score assay was 12.4%, compared with a range of 18.9% to 26.8% from other sources. The mean IBE risk from the DCIS score assay was lower regardless of E5194 eligibility. The MSKCC nomogram and DCIS score assay risk estimates were weakly correlated with each other ( P = .23) and were each moderately correlated with the other risk estimates ( P = .41-.56). When applying the radiation oncologists' treatment recommendations based on their proposed risk cutoffs, evaluating risk according to the DCIS score assay led to the highest proportion of patients recommended excision alone., Conclusions: IBE risk estimates for this general community cohort of DCIS cases vary significantly among commonly available clinical predictive tools and individual radiation oncologist estimates. Surgical margins and tumor size continue to factor prominently in radiation oncologist decision algorithms. The differences found between the IBE risk estimate methods suggests that they are not interchangeable and the methods that rely on clinicopathologic features may tend to overestimate risk., (© 2020 The Author(s).)

Purpose: To report outcomes in breast cancer patients with prior breast augmentation treated with external beam accelerated partial breast irradiation (EB-APBI) utilizing intensity-modulated radiotherapy or 3-dimensional conformal radiotherapy, both with IGRT., Materials and Methods: Sixteen stage 0/1 breast cancer patients with previous elective bilateral augmentation were treated post-lumpectomy on institutional EB-APBI trials (01185132 and 01185145 on clinicaltrials.gov). Patients received 38.5 Gy in 10 fractions over five consecutive days. Breast/chest wall pain and cosmesis were rated by patient; cosmesis was additionally evaluated by physician per RTOG criteria., Results: The median follow-up from accelerated partial breast irradiation (APBI) completion was 23.9 months (range, 1.2-58.6). Little to no change in cosmesis or pain from baseline was reported. Cosmetic outcomes at last follow-up were judged by patients as excellent/good in 81.2% (13/16), and by physicians as excellent/good in 93.8% (15/16). Ten patients (62.5%) reported no breast/chest wall pain, five (31.2%) reported mild pain, and one (6.2%) reported moderate pain. All patients remain disease free at last follow-up. The median ipsilateral breast, planning target volume (PTV), and implant volumes were 614, 57, and 333 cm(3). The median ratios of PTV/ipsilateral breast volume (implant excluded) and PTV/total volume (implant included) were 9 and 6%., Conclusion: These 16 breast cancer cases with prior bilateral augmentation treated with EB-APBI demonstrate favorable clinical outcomes. Further exploration of EB-APBI as a treatment option for this patient population is warranted.

Tumor-specific immune tolerance limits the effectiveness of cancer vaccines. In addition, tumor vaccines alone have a limited potential for the treatment of measurable tumor burdens. This highlights the importance of identifying more potent cancer vaccine strategies for clinical testing. We tested immune-modulating doses of chemotherapy in combination with a granulocyte/macrophage-colony stimulating factor (GM-CSF)-secreting, HER-2/neu (neu)-expressing whole-cell vaccine as a means to treat existing mammary tumors in antigen-specific tolerized neu transgenic mice. Earlier studies have shown that neu transgenic mice exhibit immune tolerance to the neu-expressing tumors similar to what is observed in patients with cancer. We found that cyclophosphamide, paclitaxel, and doxorubicin, when given in a defined sequence with a GM-CSF-secreting, neu-expressing whole-cell vaccine, enhanced the vaccine's potential to delay tumor growth in neu transgenic mice. In addition, we showed that these drugs mediate their effects by enhancing the efficacy of the vaccine rather than via a direct cytolytic effect on cancer cells. Furthermore, paclitaxel and cyclophosphamide appear to amplify the T helper 1 neu-specific T-cell response. These findings suggest that the combined treatment with immune-modulating doses of chemotherapy and the GM-CSF-secreting neu vaccine can overcome immune tolerance and induce an antigen-specific antitumor immune response. These data provide the immunological rationale for testing immune-modulating doses of chemotherapy in combination with tumor vaccines in patients with cancer.

HER-2/neu (neu) transgenic mice (neu-N mice), which express the nontransforming rat proto-oncogene, demonstrate immunological tolerance to neu that is similar to what is encountered in patients with neu-expressing breast cancer. We have shown previously that a significant increase in neu-specific T cells, but no induction of neu-specific antibody, is seen after neu-specific vaccination in neu-N mice. In contrast, a significant induction of both neu-specific T-cell and antibody responses is found in nontoleragenic FVB/N mice after vaccination. These mice are fully protected from a s.c. challenge with NT cells, a mammary tumor cell line derived from a spontaneous tumor that arose in a neu-N mouse, whereas neu-N mice are not. In this study, we demonstrate that CD4+ T cell-depleted FVB/N mice show no induction of neu-specific IgG after vaccination and are unable to reject an NT challenge (0 of 10 mice were tumor free). Conversely, the depletion of natural killer cells has no effect on vaccine-mediated tumor rejection (100% of mice were tumor free). In CD8+ T cell-depleted animals, where vaccine-induced neu-specific IgG titers were normal, NT growth was delayed, but only 10% of mice remained tumor free, demonstrating that neu-specific IgG alone is insufficient for protection from NT challenge. To directly assess the necessity for the combination of neu-specific cellular and humoral immune responses, severe combined immunodeficient mice were given an adoptive transfer of CTLs plus IgG derived from FVB/N mice. Animals that were given CTLs that recognized an irrelevant antigen plus neu-specific IgG developed tumors at a rate similar to CD8+ T cell-depleted FVB/N mice. Animals receiving an adoptive transfer of neu-specific CTLs plus control IgG derived from naive FVB/N mice were only partially protected from NT challenge (50% of animals were tumor free). However, only animals receiving the combination of neu-specific CTLs and neu-specific IgG were fully protected from NT challenge (100% of animals were tumor free). These studies specifically define the immunological requirements for the eradication of neu-expressing tumors in this model system, demonstrating that both cellular and humoral neu-specific responses are necessary for protection from an NT challenge. These data suggest that vaccines optimized to induce maximal T- and B-cell immunity to neu, and possibly to similar putative tumor-rejection antigens, may lead to more potent in vivo antitumor immunity.

Allelic deletions involving the short arm of chromosome 3 (3p13-21.1) have been observed frequently in cervical carcinomas. Recently, a candidate tumor suppressor gene, FHIT (Fragile Histidine Triad), was cloned and mapped to this chromosomal region (3p14.2). Abnormal FHIT transcripts have been identified previously in a variety of tumor cell lines and primary carcinomas, although their significance and the molecular mechanisms underlying their origin remain incompletely defined. In addition, integration of human papillomavirus DNA has been identified at a fragile site (FRA3B) within the FHIT locus in cervical cancer. These observations motivated us to evaluate FHIT mRNA and protein expression in cervical cancer cell lines, primary cervical carcinomas, and normal tissues. Transcripts of the expected size and sequence were the predominant species identified by reverse transcription (RT)-PCR in cultured keratinocytes and all normal tissues evaluated. In contrast, aberrant FHIT transcripts were readily demonstrated in 6 of 7 cervical carcinoma cell lines and 17 of 25 (68%) primary cervical carcinomas. Northern blot analyses demonstrated reduced or absent FHIT expression in the cervical carcinoma cell lines, particularly those with aberrant RT-PCR products. Immunohistochemical analysis of Fhit expression in cervical tissues revealed strong immunoreactivity in nonneoplastic squamous and glandular cervical epithelium and marked reduction or loss of Fhit protein in 25 of 33 (76%) primary cervical carcinomas. In those cervical cancer cell lines and primary tumors with exclusively aberrant or absent FHIT transcripts by RT-PCR, Fhit protein expression was always markedly reduced or absent. The frequent alterations in FHIT expression in many cervical carcinomas, but not in normal tissues, suggest that FHIT gene alterations may play an important role in cervical tumorigenesis.