Concurrent Treatment Group Research Articles

Optimal Treatment Strategy of Radiotherapy and Crizotinib for Patients with Brain Metastasis from ALK-Rearranged Non-Small-Cell Lung Cancer

<h3>Purpose/Objective(s)</h3> Radiotherapy and anaplastic lymphoma kinase (ALK) inhibitors are treatment options for brain metastasis (BM) in patients with ALK-rearranged non-small cell lung cancer (NSCLC). This study aimed to find the optimal treatment strategy for patients with BM from ALK-rearranged NSCLC. <h3>Materials/Methods</h3> Between 2012 and 2017, consecutive patients with BM from ALK-rearranged NSCLC treated with crizotinib and radiotherapy in our institution were reviewed and enrolled into the study. Patients were treated with sequential radiotherapy and crizotinib (upfront radiotherapy or crizotinib followed by the other at intracranial progression), or concurrent radiotherapy and crizotinib. The cumulative incidence of intracranial progression free survival (iPFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and the log-rank test was used to analyze differences between the groups. A two-sided p value ≤ 0.05 were considered statistically significant. <h3>Results</h3> Totally 41 patients were enrolled, including 24 (58.5%) with sequential treatment and 17 (41.5%) with concurrent treatment. The diagnosis-specific graded prognostic assessment (DS-GPA) score was 0-2 in 25 (60.1%) patients and > 2 in 16 (39.0%) patients, respectively. There were 13(31.7%), 17 (41.5%), and 11 (26.8%) patients treated with stereotactic radiosurgery (SRS), whole brain radiotherapy (WBRT), and WBRT with simultaneous in-field boost (SIB), respectively. The median iPFS and OS in all patients were 33.5 (95% CI 30.8-36.2) months and 63.9 (95% CI 46.0-81.9) months, respectively. There was no significant difference of iPFS or OS between the sequential treatment group and the concurrent treatment group. However, in DS-GPA scores of 0-2, the iPFS was longer in the sequential treatment group than concurrent treatment group (67.9 months vs.32.6 months, <i>P</i>=0.045), but the difference of OS was not significant between the two groups (38.9 months vs. 32.6 months, <i>P</i>=0.829). Moreover, the median iPFS of patients receiving SRS, WBRT alone, and WBRT with SIB was 33.5 months, 43.6 months, and 63.9 months (P=0.047). The corresponding median OS was not reached, 26.0 months, and 67.9 months, respectively (<i>P</i><0.001). <h3>Conclusion</h3> For patients with BM from ALK-rearranged NSCLC in our study, sequential crizotinib and brain radiotherapy for patients with DS-GPA score of 0-2 achieve better iPFS. In addition, WBRT with SIB achieves the best iPFS.

Efficacy and Safety of Radiotherapy Combined with Immunotherapy for Brain Metastases from Lung Cancer: A Meta-analysis

Immunotherapy (IT) is recommended for the treatment of advanced non-small cell lung cancer (NSCLC), while brain radiotherapy (RT) is the mainstream treatment for patients with brain metastases (BM). This study aimed to investigate the efficacy and safety of combined use of RT and IT. The date was limited to May 1, 2022, and literature searches were carried out in CNKI, Wanfang, PubMed, EMBASE and Cochrane databases. Heterogeneity was judged using the I2 test and P value. Publication bias was assessed using a funnel plot. The quality of included studies was assessed using the Newcastle-Ottawa Scale (NOS). Statistical analysis was performed using Stata 16.0 software. A total of 17 articles involving 2,636 patients were included. In the comparison of RT+IT group and RT group, no significant difference was found in overall survival (OS) (HR=0.85, 95%CI: 0.52-1.38, I2=73.9%, Pheterogeneity=0.001) and intracranial distance control (DBC) (HR=1.04, 95%CI: 0.55-1.05, I2=80.5%, Pheterogeneity<0.001), but the intracranial control (LC) in the RT+IT group was better than the RT group (HR=0.46, 95%CI: 0.22-0.94, I2=22.2%, Pheterogeneity=0.276), and the risk of radiation necrosis/treatment-related imaging changes (RN/TRIC) was higher than RT (HR=1.72, 95%CI: 1.12-2.65, I2=40.2%, Pheterogeneity=0.153). In the comparison between the RT+IT concurrent group and the sequential group, no significant difference was found in OS (HR=0.62, 95%CI: 0.27-1.43, I2=74.7%, Pheterogeneity=0.003) and RN/TRIC (HR=1.72, 95%CI: 0.85-3.47, I2=0%, Pheterogeneity=0.388) was different between the two groups. However, DBC in the concurrent treatment group was better than that in the sequential treatment group (HR=0.77, 95%CI: 0.62-0.96, I2=80.5%, Pheterogeneity<0.001). RT combined with IT does not improve the OS of NSCLC patients with BM, but also increases the risk of RN/TRIC. In addition, compared with sequential RT and IT, concurrent RT and IT improved the efficacy of DBC.

Efficacy and Safety of Concurrent Chemoradiotherapy with Docetaxel for Locally Advanced Breast Carcinoma after Modified Radical Mastectomy

Background: Breast cancer is a common term for a malignant tumor that arises from the epithelial component of the breast. Concurrent chemoradiotherapy’s efficacy and safety are controversial, considering the impact on patients' quality of life. Objectives: The aim of this study was investigating the efficacy and safety of concurrent chemoradiotherapy with docetaxel in locally advanced breast cancer who have received a modified radical mastectomy. Methods: A cohort of 110 female patients with locally advanced breast cancer were included in the present study and divided by chemoradiotherapy mode into a concurrent chemoradiotherapy group (n=58) and a sequential chemoradiotherapy group (n=52). Docetaxel was administered concurrently during radiotherapy in the concurrent group, whereas the sequential group underwent adjuvant radiotherapy 1-3 weeks after chemotherapy. Then, the two groups were compared with respect to clinical efficacy, levels of tumor markers across vascular endothelial growth factor (VEGF) and Carcinoembryonic antigen (CEA), adverse reactions, and the 3-year overall survival (OS) rate. Results: The results showed that the mean age, operation, evaluation of Post treatment VEGF (pg / mg) and Post treatment CEA (/g / L), effectiveness of treatment in two sequential and concurrent treatment groups was not significant The results showed that the amount of Prior treatment VGEF (pg / mg) and Post treatment VGEF (pg / mg) in the two groups were statistically significant difference. Which shows the positive effect of this treatment before and after the intervention. Comparison of survival time in the two groups did not show a significant difference. Conclusion: The chemotherapy protocol with a combination of cyclophosphamide, fluorouracil and epirubicin with concurrent docetaxel presented higher efficacy and prolonged the overall survival in locally advanced breast cancer patients who had undergone a radical mastectomy, while it did not significantly increase the toxicity.

Safety and efficacy of immunotherapy in combination with epigenetic therapy in an esophageal adenocarcinoma model.

335 Background: There is a critical need to develop effective therapeutic approaches for patients with esophageal cancer, a leading cause of cancer mortality. Recently, immune checkpoint blockade (ICB) has demonstrated modest survival benefit in gastroesophageal cancer patients. Epigenetic therapies, including DNA methyltransferases (DNMT) and histone deacetylases (HDACs), have shown to enhance tumor immune recognition by directly upregulating antigen presentation and by activation of type-1 interferon response triggered by cytoplasmic double-stranded RNA, a phenomenon known as viral mimicry. In other cancer models, epigenetic therapy has shown early promise by enhancing the effectiveness of ICB via addictive antiproliferative effects, enhanced immune activation and reversal of T cell exhaustion towards a memory-effector T-cell phenotypes. Methods: Esophagojejunostomy was performed to induce gastroduodenojejunal reflux in rats, leading to development of EAC. At 32 weeks postop, animals were randomized into eight treatment and control groups: placebo ± radiation, epigenetic treatment ± radiation, immunotherapy treatment ± radiation, and concurrent epigenetic and immunotherapy ± radiation. Animals underwent three 14 day cycles of epigenetic treatment or placebo. Each cycle consisted of one week of DNMT treatment or placebo at a dose of 0.5mg/kg, followed by one week of HDAC treatment or placebo at a dose of 2mg/kg. Animals received one 3mg/kg dose of PD1 inhibitor or placebo on day 12 of each cycle. Safety and efficacy were evaluated via objective health assessments, change in tumor volume, immunofluorescent labeling and RT-PCR. Results: Seventy of 74 randomized animals reached study end-point with no significant differences in mortality observed across groups (p = 0.556). There were no significant differences in observed health scores or weights between all groups (p = 0.431 and p = 0.882, respectively). Pre to posttreatment, mean MRI tumor volume increased by 263.1% and 90.9% in the placebo and the placebo plus radiation groups, respectively. The largest tumor reduction was observed in the concurrent treatment groups, 84.5% and 61.8% with and without radiation, respectively. Additionally, independent epigenetic and immunotherapy treatments with or without radiation also exhibited decrease in tumor volume, but to a lesser extent than the concurrent regimens (p = 0.005). Immunofluorescent labeling demonstrated a significant increase in CD3+ CD8+ T cells in all treatment groups compared to placebo (p = &lt; 0.001). Gene expression displayed upregulation of CD206 (p = 0.002), TNFα (p = &lt; 0.001), and Arg1 (p = &lt; 0.001) in treatment arms compared to placebo. Conclusions: This study establishes addictive antitumor efficacy and enhanced immune sensitization for a concurrently sequenced treatment, combining epigenetic therapy and radiation with immunotherapy, to treat EAC.

Treatment effect of hemifacial dysplasia by injecting transplantation of autologous tissue in the second stage surgery for total auricle reconstruction

Objective: To observe the treatment effect of hemifacial dysplasia by injecting transplantation of autologous dermis and fat granules in the second stage surgery for total auricle reconstruction. Methods: From March 2013 to March 2018, 57 patients with unilateral microtia and mild-to-moderate hemifacial dysplasia were divided into concurrent treatment group (32 cases, including 13 females and 19 males and aged 6-33 years old with an average age of 12.5 years) and traditional treatment group (25 cases, including 10 females and 15 males and aged 6-21 years old with an average age of 11.3 years) according to the different surgical methods. Modified Nagata method of auricular reconstruction was chosen, in the second stage surgery (cranial ear angle plasty), patients in concurrent treatment group received the treatment of hemifacial dysplasia with autologous dermal and fat injection transplantation at the same time; Patients in traditional treatment group only received cranial ear angle plasty. Statistical analysis of the two groups of patients was carried out for the average operation time, the average length of hospital stay, the incidence of common complications and postoperative satisfaction rate. SPSS 21.0 software was used for statistical analysis. Results: The mean operation time of the concurrent treatment group (282.0±3.4)min was longer than that of the traditional treatment group (243.0±3.1)min, and the difference was statistically significant (t=9.884, P<0.05). There were no statistically significant differences in the average length of stay between the the concurrent treatment group (9.4±0.3)d and the traditional treatment group(9.5±0.2)d, t=0.256, P>0.05. There were no statistically significant differences in the incidence of common surgical complications between the concurrent treatment group (12.5%, 4/32) and the traditional treatment group(12.0%, 3/25), χ2=0, P>0.05. Postoperative satisfaction rate of the concurrent treatment group(90.6%, 29/32) was significantly higher than that of the traditional treatment group(56.0%, 14/25), the difference was statistically significant (χ2=9.081, P<0.05). Conclusions: Auricular reconstruction with treatment of hemifacial dysplasia should not significantly increase the average length of stay and the incidence of common complications compared with auricular reconstruction alone. Although the operation time is slightly extended, the scheme of concurrent treatment can reduce the times of operations, save medical resources and increase the satisfaction rate of patients.

Anti-preneoplastic and anti-fibrogenetic effect of zinc oxide nanoparticles (ZnO NPs) against experimental hepatocarcinogenesis

To investigate the effects of zinc oxide nanoparticles (ZnO NPs) against hepatocarcinogenesis, the present study was conducted. To induce hepatocarcinogenesis rats with Diethylnitrosamine (DEN) at 100 mg/kg body weight intraperitoneally on Day 1 followed by 0.01 % DEN in drinking water ad libitum for 60 days. Zinc oxide nanoparticles as aqueous suspension was gavaged orally at a dose rate of 25 mg/kg body weight for 15 days prior to DEN treatment in ZnO NPs pre-treatment group and concurrently with DEN for 60 days in ZnO NPs concurrent treatment group. DEN induced severe hepatic damage and formation of preneoplastic altered hepatic foci by 30th day and severe fibrotic tissue proliferation with development of hepatic adenoma and carcinoma by 60th day. In pre-treatment and concurrent treatment groups, ZnO NPs reduced the extent of hepatic damage, prevented the formation of altered hepatic foci by 30th day and drastically reduced the extent of fibrotic tissue proliferation by 60th day which were determined through routine histopathology of hepatic tissue and special staining techniques alongside gross observation of liver.

The Efficacy of Concurrent or Sequential Intravenous and Intratympanic Steroid for Idiopathic Sudden Sensorineural Hearing Loss

Objective: The purpose of this retrospective study was to investigate the difference in treatment outcomes for patients with idiopathic sudden sensorineural hearing loss (SSNHL) undergoing concurrent or sequential intravenous (IV) and intratympanic (IT) steroid therapies. Methods: Patients with idiopathic SSNHL admitted to Taipei Veterans Hospital from August 2011 to August 2012 were enrolled. Patients were treated with both IV dexamethasone 5 mg b.i.d. for 5 days, then tapered over 6 days, and IT injections of dexamethasone 5 mg daily. The administration of IV and IT steroids was given either concurrently or sequentially (IV steroid was administered from days 1–5 followed by IT steroid treatment starting on day 4 or day 5). The hearing outcomes of the concurrent and sequential groups were analyzed. Results: Overall, after ≥2 months following treatment, across frequencies ranging from 250 to 8,000 Hz and pure-tone average (PTA) assessments, hearing improvements were similar between treatment groups, except at the frequencies of 4,000 and 8,000 Hz where the concurrent treatment group had greater hearing gain than the sequential group (4,000 Hz: 30.68 ± 28.96 vs. 14.52 ± 24.06 dB, respectively, p = 0.042; 8,000 Hz: 22.62 ± 23.59 vs. 7.67 ± 21 dB, p = 0.030). Across frequencies and PTA assessments, a similar percentage of patients had ≥20-dB gains in hearing compared with patients treated sequentially, except at 8,000 Hz where a greater percentage of patients in the concurrent group (57.1%) than the sequential group (23.3%) (p = 0.014) had ≥20-dB hearing gains. Conclusion: The findings suggest that both concurrent and sequential treatment improve hearing in patients with idiopathic SSNHL, and that concurrent treatment may show greater benefit than sequential therapy, particularly at high frequencies.

Efficacy of φkm18p phage therapy in a murine model of extensively drug-resistant Acinetobacter baumannii infection.

PurposeFew effective antibiotics are available for treating extensively drug-resistant Acinetobacter baumannii (XDRAB) sepsis. Phage therapy may show potential in treating XDRAB infections.Materials and methodsWe studied φkm18p phage therapy in BALB/c and C57BL/6 mice models of XDRAB bacteremia.ResultsWe observed survival rates of nearly 100% in groups given phage therapy concurrent with XDRAB at different multiplicities of infection. In mice that received phage therapy after a 1-hour delay, the survival rate decreased to about 50%. The bacterial load in the blood decreased from 108 to 102 and 103 colony-forming units (CFU)/mL in the concurrent treatment group. In the phage therapy group, the levels of the cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), were low at 3 hours after infection. Although some phage-resistant mutants were isolated after phage therapy, a cytotoxicity study showed that they had reduced fitness.ConclusionPhage therapy in XDRAB bacteremia increased the animal survival rates, decreased the bacteremia loads, and decreased the levels of inflammatory markers TNF-α and IL-6. However, the reduced therapeutic effect with delayed administrations may be a concern in developing a successful phage therapy for treating acute infections of multidrug-resistant pathogens.

P3.17-03 Survival and Side Effects in Non-Small Cell Lung Cancer Patients Treated with Combination of Chemotherapy and Conformal Radiotherapy

Combined modality therapy is standard of care for patients with unrespectable locally advanced non-small cell, however, insufficient data are available regarding what is the best combination of chemotherapy and radiotherapy. s: To evaluate the treatment results, study of 85 patients was randomly assigned to one of the two treatment arms. In the sequential arm, 45 patients had previously received sequential chemotherapy with 4 cycles of carboplatin and etoposide followed by conformal radiotherapy (RT). In the second concurrent arm, 40 patients received concomitant chemotherapy of cisplatine and etoposide and conformal RT, followed by two cycles of consolidation chemotherapy of carboplatine and etoposide. We described all phases of the conformal RT. s: From October 2005 to April 2008, 85 patients were enrolled. The median survival was 13 months for the patients in the sequential arm and 19 months for those in the concurrent treatment arm. The differences were statistically significant (log-rank test p=0.0039) Figure 1. The disease-free survival was 9 months in the sequential arm and 16 months in the concurrent treatment group. The differences were statistically significant (log-rank test p=0.0023). Treatment-related toxicities were assessed according RTOG/EORTC criteria. Acute esophagitis and incidence of neutropenia were higher in the concurrent arm.. Grade 3 esophagitis was characteristic only for concurrent treatment and it was reason for radiotherapy interruption, but no longer than 7 days. s: Given the higher toxicity in the concurrent-consolidation schedule, it should be reserved for patients younger than 70 years, having good performance status and minimal weight loss.

What Is the Optimal Adjuvant Treatment Sequence for Node-Positive Endometrial Cancer? Results of a National Cancer Database Analysis.

The optimal sequence of administering chemotherapy (CT) and radiation treatment (RT) in women with node-positive endometrial carcinoma (EC) remains controversial. We used the National Cancer Database to evaluate overall survival (OS) in women with advanced EC receiving different sequences of adjuvant therapy. The National Cancer Database was queried for female adults with International Federation of Gynecology and Obstetrics 2009 stage IIIC1 to IIIC2 EC diagnosed from 2004 to 2012 treated with hysterectomy and adjuvant CT and RT. Overall survival was compared between sequential treatment (CT followed by RT) and concurrent treatment (CT and RT within 4 weeks). χ tests assessed differences by sequence and various clinical variables. Log-rank test and Cox proportional hazards models evaluated OS. Risk factors related to OS were identified by univariate and multivariate analyses. Of 1826 patients, 67% (1218) received sequential treatment and 33% (608) received concurrent treatment. The median follow-up was 49.2 months. The sequential treatment group had a better 5-year OS (67% [95% confidence interval = 64%-70%]) than the concurrent treatment group (62% [95% confidence interval = 57%-66%]) (P = 0.004). On multivariate analysis, the strongest predictors of worse OS were increasing age (hazard ratio [HR] = 1.04 [1.02-1.06], P = 0.0003), type 2 versus type 1 EC (HR = 1.60 [1.06-2.43], P = 0.03), grade 3 versus 1 (HR = 2.64 [1.23-5.67], P = 0.01), residual disease or positive margin versus negative margin (HR = 2.25 [1.43-3.56], P = 0.0005), and concurrent versus sequential treatment (HR = 1.67 [1.15-2.40], P = 0.006). This study suggests that upfront CT followed by RT may be a better treatment sequence for adjuvant therapy in women with advanced EC.

Impact of Different Timing of Radiation Therapy on Patients With Brain Metastases from Epidermal Growth Factor Receptor-Mutant Non–small Cell Lung Cancer

To perform a retrospective analysis of patients with brain metastases (BM) from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) to evaluate the preferred treatment timing of EGFR-tyrosine kinase inhibitors (TKIs) in this population. Of 94 initial or recurrent patients diagnosed BM from EGFR-mutant NSCLC between Jan 1, 2012, and Jun 31, 2016, 30 received upfront brain RT followed by EGFR-TKI, 39 EGFR-TKI combined with concurrent brain RT, and 25 upfront EGFR-TKI then brain RT. Disease-specific-graded prognostic assessment was similar among all 3 groups. The primary endpoint was overall survival (OS), and the second endpoint was intracranial progression-free survival. Although the median OS was not significantly different among the upfront RT, concurrent treatment, and upfront EGFR-TKI groups (29.0 vs 24.0 vs 17.0 months; P=0.186), however, it was longer in the upfront RT group compared with the upfront EGFR-TKI group (P=0.035). On subgroup analysis, the exon 19 deletions patients had longer OS than the exon 21 mutations patients in upfront EGFR-TKI group (23.0 vs 15.0 months; P=0.048), but the upfront RT (34.0 vs 23.0 months; P=0.186) and the concurrent treatment groups (24.0 vs 13.0 months; P=0.827) did not. According to multivariate COX analysis, KPS (≥ 70) and intracranial metastasis alone was associated with a longer OS. The median intracranial progression-free survival was significantly improved in patients receiving upfront RT compared with those receiving concurrent treatment or upfront EGFR-TKI (not reached vs 40.0 vs 9.0 months; P=0.003). The present study suggests that the use of upfront brain radiotherapy, and the deferral of EGFR-TKI may result in superior OS in patients with brain metastases from EGFR-mutant NSCLC. Also, upfront brain radiotherapy management could significantly reduce the risk of intracranial progression. A prospective, multi-institutional, randomized trial of upfront EGFR-TKI then RT versus upfront RT followed by EGFR-TKI is urgently needed, especially based on different subgroup population.

Impact of different timing of radiation therapy in patients with brain metastases from epidermal growth factor receptor-mutant non-small cell lung cancer.

e20667 Background: To perform a retrospective analysis of patients with brain metastases (BM) from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) to evaluate the preferred treatment timing of EGFR-tyrosine kinase inhibitors (TKIs) in this population. Methods: Of 94 initial or recurrent patients diagnosed BM from EGFR-mutant NSCLC between Jan 1, 2012, and Jun 31, 2016, 30 received upfront brain RT followed by EGFR-TKI, 39 EGFR-TKI combined with concurrent brain RT, and 25 upfront EGFR-TKI then brain RT. Disease-specific-graded prognostic assessment was similar among all 3 groups. The primary endpoint was overall survival (OS), and the second endpoint was intracranial progression-free survival. Results: Although the median OS was not significantly different among the upfront RT, concurrent treatment, and upfront EGFR-TKI groups (29.0 vs 24.0 vs 17.0 months; P = 0.186), however, it was longer in the upfront RT group compared with the upfront EGFR-TKI group (P = 0.035). On subgroup analysis, the exon 19 deletions patients had longer OS than the exon 21 mutations patients in upfront EGFR-TKI group (23.0 vs 15.0 months; P = 0.048), but the upfront RT (34.0 vs 23.0 months; P = 0.186) and the concurrent treatment groups (24.0 vs 13.0 months; P = 0.827) did not. According to multivariate COX analysis, KPS (≥ 70) and intracranial metastasis alone was associated with a longer OS. The median intracranial progression-free survival was significantly improved in patients receiving upfront RT compared with those receiving concurrent treatment or upfront EGFR-TKI (not reached vs 40.0 vs 9.0 months; P = 0.003). Conclusions: The present study suggests that the use of upfront brain radiotherapy, and the deferral of EGFR-TKI may result in superior OS in patients with brain metastases from EGFR-mutant NSCLC. Also, upfront brain radiotherapy management could significantly reduce the risk of intracranial progression. A prospective, multi-institutional, randomized trial of upfront EGFR-TKI then RT versus upfront RT followed by EGFR-TKI is urgently needed, especially based on different subgroup population.

Preliminary experience of the concurrent use of radiosurgery and T-DM1 for brain metastases in HER2-positive metastatic breast cancer.

This is preliminary study assessing the efficacy and safety of concurrent use of radiation therapy (RT) and T-DM1 for the treatment of brain metastases (BM) in patients with HER2-positive metastatic breast cancer (BC). We retrospectively studied 12 patients treated for BM at the Institut Curie in 2014-2015 with T-DM1 and concurrent (4) or sequential (8) radiosurgery with or without whole brain irradiation. The following variables were studied: local control, clinical and radiological response as well as early and late side effects. The mean age of the population was 38 years at the time of diagnosis of BC and 46 years at of BM. All patients were with good PS. The response rate of the concurrent treatment group was 75 % with 1 complete response, 1 partial response, one stable disease and 1 progression. Comparatively, the response rate in the sequential group was as follows: two complete responses, two partial responses, six cases of stable disease and two cases of local progression. No patient experienced interruption of irradiation because of side effects. About 50 % of patients were asymptomatic after treatment. Radiation necrosis was observed in 50 % of patients in the concurrent group and 28.6 % of patients in the sequential group with a similar rate of oedema in the two groups. We found that the combination of T-DM1 and radiosurgery was feasible but can increase the incidence of radiation necrosis. Larger prospective studies with longer follow-up are needed to more clearly evaluate this association.

Abstract P3-12-20: The impact of everolimus on radiation-induced pulmonary fibrosis in wistar albino rats: Results of an experimental study

Abstract Objectives: This study was performed to evaluate the effects of everolimus on pulmonary fibrosis, given concurrently or sequential with irradiation in rats. Materials and Methods: Forty female Wistar albino rats were randomized into five groups. The first group (Group 1: sham) was observed with identical conditions of the animals in other groups. The second group (Group 2) had only everolimus application. The third group (Group 3) had thoracic irradiation first and they had everolimus injection 22 hours after radiotherapy. The fourth group (Group 4) had irradiation to whole thoracic region in 2 hours of following everolimus administration. The last group (Group 5) had irradiation to whole thoracic region. As an end point the percentage of lung with fibrosis for each rat was quantified with image analysis of histological sections of the lung. Groups were compared using the linear regression method, Fisher's exact and chi-square tests were used to assess the association between treatment groups. Results: There was a statistically significant difference in the distribution of fibrosis scores among all groups (p=0.0022). Linear regression analyses revealed that all treatment groups showed an increased risk of lung fibrosis compared to control group. Group 2 (p=0.0020), group 3 (p&amp;lt;0.0001), group 4 (p&amp;lt;0.0001), and group 5 (p=0.0002). Chi-square test demonstrated that there was no statistically significant difference between the sequentially and concurrent treatment groups. Conclusion: This experimental study showed that of everolimus by itself may lead pulmonary fibrosis and addition to radiotherapy either sequentially or concomitantly increased the severity of the lung damage in rats. Keywords: Radiotherapy, everolimus, rats, pulmonary fibrosis. Citation Format: Eren MF, Ay Eren A, Yücel B, Elagöz S, Özgüven Y, Altun A, Kiliçkap S, Matsuno R, Bese N. The impact of everolimus on radiation-induced pulmonary fibrosis in wistar albino rats: Results of an experimental study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-12-20.

Prognostic Factors and Survival in Non-Small Cell Lung Cancer Patients Treated with Chemoradiotherapy.

BACKGROUND:According to the literature, performance status, stage-tumor dimension and nodal status, weight loss, were the most important prognostic factors for survival in patients with locally advanced non-small cell lung cancer.AIM:To evaluate the treatment results and the prognostic variables in our patients treated with sequential and concurrent chemoradiotherapy.MATERIAL AND METHODS:In the study 85 patients were randomly assigned to one of the two treatment arms. In the sequential arm, 45 patients had previously received sequential chemotherapy with 4 cycles of and etoposide followed by conformal radiotherapy (RT). In the second concurrent group, 40 patients received concomitant chemotherapy of cisplatine and etoposide and conformal RT, followed by two cycles of consolidation chemotherapy of carboplatine and etoposide. We described all phases of the conformal three dimensional (3-D) RT.RESULTS:From October 2005 to March 2008, 93 patients were enrolled. Eight patients were not eligible, seven had stage IV and one patient had pleural effusion. They were all initially considered to have stage IIIB disease. The median survival was 13 months for the patients in the sequential arm and 19 months for those in the concurrent treatment arm. The differences were statistically significant (log-rank test p=0.0039). The disease-free survival was 9 months in the sequential arm and 16 months in the concurrent treatment group. The differences were statistically significant (log-rank test p=0.0023). We found that the following prognostic factors significantly influenced the survival in lung cancer patients treated with conservative method: - age, p<0.05; - performant status, p<0.001; - weight loss, p<0.001; tumor dimension, p<0.05; and - nodal involvement, p<0.05.CONCLUSION:In our study, the dose-limiting toxicity, esophagitis was reduced by performing conformal radiotherapy. Conformal thoracic radiotherapy and new radiotherapy technics, such as respiratory gated radiotherapy, allow dose escalating and may probably improve survival and local control in lung cancer patients.

Influence of Prognostic Factors on Survival in Locally Advanced Non-Small Cell Lung Cancer Patients Treated with Combination of Chemoradiotherapy

According to the literature, performance status, stage-tumor dimension and nodal status, weight loss, were the most important prognostic factors for survival in patients with locally advanced non-small cell lung cancer. To evaluate the treatment results and prognostic variables in our patients, study of 85 patients was randomly assigned to one of the two treatment arms. In the sequential arm, 45 patients had previously received sequential chemotherapy with 4 cycles of and etoposide followed by conformal radiotherapy (RT). In the second concurrent group, 40 patients received concomitant chemotherapy of cisplatine and etoposide and conformal RT, followed by two cycles of consolidation chemotherapy of carboplatine and etoposide. We described all phases of the conformal three dimensional (3-D) RT. From October 2005 to April 2008, 85 patients were enrolled. Eight patients were not eligible, seven had stage IV and one patient had pleural effusion. They were all initially considered to have stage IIIB disease. The median survival was 13 months for the patients in the sequential arm and 19 months for those in the concurrent treatment arm. The differences were statistically significant (log-rank test p=0.0039). The disease-free survival was 9 months in the sequential arm and 16 months in the concurrent treatment group. The differences were statistically significant (log-rank test p=0.0023). We found that the following prognostic factors significantly influenced the survival in lung cancer patients treated with conservative method: (1) age: p<0.05; (2) Performance status: p<0.001; (3) Weight loss: p<0.001; (4) Tumor dimension: p<0.05; (5) Nodal involvement: p<0.05 Conclusions: Given the higher toxicity in the concurrent-consolidation schedule, it should be reserved for patients younger than 70 years, having good performance status and minimal weight loss. Also we highly recommend precisely define the stage of disease and the prognostic factors in lung cancer patients for giving better treatment.

Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomised, controlled, phase 3 trial

Neoadjuvant chemotherapy with trastuzumab for patients with HER2-positive breast cancer can produce a pathological complete response in the breast in 30-65% of patients. We investigated the effect of the timing of trastuzumab administration with anthracycline and taxane neoadjuvant chemotherapy. This randomised trial was done at 36 centres in the USA and Puerto Rico. Women with operable HER2-positive invasive breast cancer were randomly assigned (1:1) with a biased coin minimisation algorithm, stratified for age, tumour size, and hormone receptor status. Neither patients nor investigators (except for a cardiac safety review panel) were masked to treatment assignment. Patients randomly assigned to sequential treatment received fluorouracil 500 mg/m(2), epirubicin 75 mg/m(2), and cyclophosphamide 500 mg/m(2) (FEC-75) on day 1 of a 21-day cycle for four cycles followed by paclitaxel 80 mg/m(2) and trastuzumab 2 mg/kg (after a 4 mg/kg loading dose) once per week for 12 weeks, while those randomly assigned to the concurrent treatment group received paclitaxel and trastuzumab once per week for 12 weeks followed by four cycles of FEC-75 (on day 1 of each 21-day cycle) and once-weekly trastuzumab, in the same doses as the sequential group. Surgery, including evaluation of the axilla, was done within 6 weeks of completion of neoadjuvant treatment. The primary outcome was the percentage of patients who had a pathological complete response in the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT00513292. From Sept 15, 2007, to Dec 15, 2011, 282 women were enrolled (140 in the sequential group, 142 in the concurrent group). Two patients in the sequential group withdrew consent before starting treatment. 78 of 138 (56·5%, 95% CI 47·8-64·9) patients who received sequential treatment had a pathological complete response in the breast versus 77 of 142 (54·2%, 95% CI 45·7-62·6) who received concurrent treatment (difference 2·3%, 95% CI -9·3 to 13·9). No treatment-related deaths occurred. The most common severe toxic effects were neutropenia (35 [25·3%] of 138 patients in the sequential group vs 45 [31·7%] of 142 patients in the concurrent group) and fatigue (six [4·3%] vs 12 [8·5%]). Left ventricular ejection fraction dropped below the institutional lower limit of normal at week 12 in one (0·8%) of 130 patients who received sequential treatment and four (2·9%) of 137 patients who received concurrent treatment; by week 24, it had dropped below this limit in nine (7·1%) of 126 patients and in six (4·6%) of 130 patients, respectively. Concurrent administration of trastuzumab with anthracyclines offers no additional benefit and is not warranted. US National Cancer Institute.

Highlights from Recent Cancer Literature

Highlights from Recent Cancer Literature

Lipids Behavior and Adverse Effects for Oral Antidiabetic Agents in Patients with Type2 Diabetes Treated with Sulfonylureas Alone Based on Systematic Review

The secondary and adverse effects when biguanides, alpha-glycosidase inhibitor or thiazolidine derivative was used with sulphonylurea agent (SU) as compared with those with SU alone in Type 2 diabetes patients by using Systematic Review. Two-agent concurrent treatment groups, taken from studies in which subjects were assigned to a group given only a sulfonylurea agent and a group given a sulfonylurea agent with the other glycemic control agent (combination of a sulfonylurea agent and a biguanide agent (I), combination of a sulfonylurea agent and an alpha-glucosidase inhibitor (II), and combination of a sulfonylurea agent and thiazolidinedione (III)), were studied in a randomized controlled trial. The secondary efficacy outcome measures were total cholesterol (TC), triglyceride (TG), HDL-C, LDL-C, and change in body weight. The incidence of hypoglycemia, feeling of fullness, diarrhea, liver dysfunction, and edema was investigated as a safety outcome measure, and the clinical significance of concurrent treatment with a sulfonylurea agent in addition to the other glycemic control agent was investigated. With respect to (II), an antidiabetic effect was showed. As for (III), it had the disadvantage of increased body weight. Furthermore, increase of HDL-C levels, in particular, was observed. The improving effect of (III) on serum lipids may be clinically effective for considering the pathologic condition of diabetes, which is often complicated by hyperlipidemia.

Concurrent versus sequential methods for labor induction at term

Objective To determine the efficacy and safety of the concurrent administration of oxytocin and prostaglandin E2 (PGE2) for induction of labor at term, prompt delivery, and good maternal and neonatal outcomes. Methods In this comparative cohort study of 70 women conducted in Pakistan, 35 were given oxytocin and PGE2 concurrently and 35 were given the drugs sequentially for labor induction. Two-sample t tests and × 2 tests were used for the evaluation of continuous and categorical data, respectively. Results The mean induction to delivery time was shorter by 2.4 h in the concurrent treatment group ( P < 0.001), and the proportion of vaginal deliveries was higher in that group. Conclusion The concurrent method of induction of labor resulted in shorter induction to delivery time and a higher proportion of vaginal deliveries.