Efficacy Of Adjuvant Treatment Research Articles

Survival benefit of adjuvant treatment for ampullary cancer with lymph nodal involvement: A systematic review and meta-analysis

BackgroundThe efficacy of adjuvant treatment (AT) in ampullary cancer (AmC) remains controversial. This systematic review and meta-analysis aimed to evaluate the role of AT for AmC. Data sourcesA comprehensive systematic search was performed in PubMed, EMBASE, Cochrane Library, and Web of Science databases. Studies comparing overall survival (OS) and recurrence-free survival (RFS) of patients who underwent AT or not following AmC resection were included. ResultsA total of 3971 patients in 21 studies were analyzed. Overall pooled data showed no significant difference in effect on the OS by AT [hazard ratio (HR) = 0.998, 95% confidence interval (CI): 0.768–1.297]. No significant difference in recurrence between the AT and non-AT (nAT) groups was noted (HR = 1.158, 95% CI: 0.764–1.755). In subgroup analysis, patients who received AT showed favorable outcomes in the OS compared with those who received nAT in nodal-positive AmC (HR = 0.627, 95% CI: 0.451–0.870). Neither AT consisted of adjuvant chemotherapy with radiotherapy (HR = 0.804, 95% CI: 0.563–1.149) nor AT with adjuvant chemotherapy (HR = 0.883, 95% CI: 0.642–1.214) showed any significant effect on the OS. ConclusionsThe effect of AT in AmC on survival and recurrence did not show a significant benefit. Furthermore, effectiveness according to AT strategies did not show enhancement in survival. AT had an advantage in survival compared with nAT strategy in nodal-positive AmC. In cases of AmC with positive lymph nodal involvement, AT may be warranted regardless of detailed strategies.

Adjuvant PD-1 Checkpoint Inhibition in Early Cutaneous Melanoma: Immunological Mode of Action and the Role of Ultraviolet Radiation.

Melanoma ranks as the fifth most common solid cancer in adults worldwide and is responsible for a significant proportion of skin-tumor-related deaths. The advent of immune checkpoint inhibition with anti-programmed death protein-1 (PD-1) antibodies has revolutionized the adjuvant treatment of high-risk, completely resected stage III/IV melanoma. However, not all patients benefit equally. Current strategies for improving outcomes involve adjuvant treatment in earlier disease stages (IIB/C) as well as perioperative treatment approaches. Interfering with T-cell exhaustion to counteract cancer immune evasion and the immunogenic nature of melanoma is key for anti-PD-1 effectiveness. Yet, the biological rationale for the efficacy of adjuvant treatment in clinically tumor-free patients remains to be fully elucidated. High-dose intermittent sun exposure (sunburn) is a well-known primary risk factor for melanomagenesis. Also, ultraviolet radiation (UVR)-induced immunosuppression may impair anti-cancer immune surveillance. In this review, we summarize the current knowledge about adjuvant anti-PD-1 blockade, including a characterization of the main cell types most likely responsible for its efficacy. In conclusion, we propose that local and systemic immunosuppression, to some extent UVR-mediated, can be restored by adjuvant anti-PD-1 therapy, consequently boosting anti-melanoma immune surveillance and the elimination of residual melanoma cell clones.

MFOLFIRINOX versus mFOLFOX 6 as adjuvant treatment for high-risk stage III colon cancer (FROST trial): Study protocol for an open label, multicenter, randomized, phase II study.

TPS230 Background: Patients with high-risk stage III colon cancer have a significantly poorer prognosis than those with stage II or low-risk stage III colon cancer. Despite this distinction, most guidelines recommend similar adjuvant treatment approaches for all stages, and there is a dearth of research focusing on high-risk stage III colon cancer and the potential for improved prognosis through more intensive adjuvant treatment. Given the proven efficacy of triplet chemotherapy in metastatic colorectal cancer, this study aims to assess the effectiveness and toxicity of modified 5-fluoropyrimidine (5-FU)/leucovorin plus irinotecan and oxaliplatin (mFOLFIRINOX) in comparison with the current standard of care—modified oxaliplatin and 5-FU (mFOLFOX-6)—as an adjuvant treatment for patients diagnosed with high-risk stage III colon cancer. Methods: This multicenter, randomized (1:1), open-label, phase II trial aims to compare the adjuvant treatment efficacy of mFOLFIRINOX and mFOLFOX-6 in patients with high-risk stage III colon cancer. The trial aimed to enroll 312 eligible patients aged between 20 and 70 years with an Eastern Cooperative Oncology Group performance status of 0-2, or between 70 and 75 years with an Eastern Cooperative Oncology Group performance status of 0. All patients underwent radical resection and were randomized into two arms: Arm A experimental arm, received 12 cycles of mFOLFIRINOX every 2 weeks, while arm B, the reference arm, received 12 cycles of mFOLFOX 6 every 2 weeks. The primary endpoint of this study was the 3-year disease-free survival, whereas the secondary endpoints included assessing the 3-year overall survival and treatment toxicity. Discussion: The Frost trial is expected to elucidate the safety and oncologic efficacy of mFOLFIRINOX compared to mFOLFOX 6 as adjuvant treatment for high-risk stage III colon cancers, and provide evidence about this treatment, and contribute to improve the prognoses ultimately. Clinical trial information: NCT05179889 .

Contrasting clinical outcomes and socio-economic impact of young versus elderly-onset oral squamous cell carcinoma, a novel health economic analysis.

The incidence of young-onset oral squamous cell carcinoma (OSCC) is growing, even among non-smokers/drinkers. The effects of adverse histopathological features on long-term oncologic outcomes between the young and old are controversial and confounded by significant heterogeneity. Few studies have evaluated the socio-economic impact of premature mortality from OSCC. Our study seeks to quantify these differences and their economic impact on society. Four hundred and seventy-eight young (<45 years) and 1660 old patients (≥45 years) with OSCC were studied. Logistic regression determined predictors of recurrence and death. Survival analysis was calculated via the Kaplan-Meier method. A separate health economic analysis was conducted for India and Singapore. Years of Potential Productive Life Lost (YPPLL) were estimated with the Human Capital Approach, and premature mortality cost was derived using population-level data. Adverse histopathological features were seen more frequently in young OSCC: PNI (42.9% vs. 35%, p = 0.002), LVI (22.4% vs. 17.3%, p = 0.013) and ENE (36% vs. 24.5%, p < 0.001). Although 5-year OS/DSS were similar, the young cohort had received more intensive adjuvant therapy (CCRT 26.9% vs. 16.6%, p < 0.001). Among Singaporean males, the premature mortality cost per death was US $396,528, and per YPPLL was US $45,486. This was US $397,402 and US $38,458 for females. Among Indian males, the premature mortality cost per death was US $30,641, and per YPPLL was US $595. This was US $ 21,038 and US $305 for females. Young-onset OSCC is an aggressive disease, mitigated by the ability to receive intensive adjuvant treatment. From our loss of productivity analysis, the socio-economic costs from premature mortality are substantial. Early cancer screening and educational outreach campaigns should be tailored to this cohort. Alongside, more funding should be diverted to genetic research, developing novel biomarkers and improving the efficacy of adjuvant treatment in OSCC.

Abstract IA003: ctDNA Guiding adjuvant treatment in early stage colon cancer: Are we moving the needle?

Abstract My presentation will summarize the accumulating evidence on the ability of circulating tumor DNA to detect minimal residual disease and track adjuvant treatment efficacy in colorectal cancer and the potential for ctDNA to reshape the adjuvant treatment paradigm. I will also discuss the rationale and results of the DYNAMIC trial (ctDNA-guiding adjuvant therapy study in stage II colon cancer) and other ongoing ctDNA-based trials. Citation Format: Jeanne Tie. ctDNA Guiding adjuvant treatment in early stage colon cancer: Are we moving the needle? [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr IA003.

PMON171 DRD2 Agonist Cabergoline Abolished the Escape Mechanism Induced by mTOR Inhibitor Everolimus in Pituitary Neuroendocrine Tumoral Cells

Abstract PI3K-AKT-mTOR inhibitors have been proposed as alternative therapeutic strategy for tumors resistant to conventional drugs. The mammalian target of rapamycin (mTOR) inhibitor everolimus has been shown to display antiproliferative effects on a wide spectrum of tumors. In vitro studies demonstrated that everolimus inhibited pituitary neuroendocrine tumors (PitNETs) cell growth and vitality in a subset of patients. Sensitivity to everolimus has been demonstrated to be reduced by an escape mechanism that increases AKT phosphorylation (p-AKT), leading to pro-survival pathway activation. This limited efficacy of everolimus due to AKT re-activation could be overtaken by upstream AKT phosphorylation inhibition. Given it was recently demonstrated that DRD2 mediates a reduction of p-AKT in a subset of NF-PitNETs and in rat prolactin-secreting tumor cells MMQ through a β-arrestin 2-dependent mechanism, the aim of the present work was to test the efficacy of adjuvant treatment with cabergoline in increasing sensitivity of human primary cultured NF-PitNET cells to antiproliferative effects of everolimus. In addition, to test a possible role of β-arrestin2. We found that 9 out of 14 NF-PitNETs were resistant to everolimus 1 nM, but the combined treatment with cabergoline inhibited cell proliferation in 7 out of 9 tumors (-31.4 ± 9.9%, p &amp;lt; 0.001 vs basal), increased p27 and reduced cyclin D3 expression. In everolimus unresponsive NF-PitNETs group, 3 h everolimus treatment determined a significant increase of p-AKT/total-AKT ratio (+2.1-fold, p &amp;lt; 0.01, vs basal), and this effect was reverted by cabergoline cotreatment in all tested samples. To investigate the molecular mechanism involved, we used MMQ cells as a model of everolimus escape mechanism. Indeed, 1nM everolimus did not affect MMQ cells proliferation due to an increase of p- AKT/total-AKT ratio (+1.53 ± 24%, p&amp;lt;0.001 vs basal), whereas cabergoline reduced cell proliferation (-22.8 ± 6.8%, p&amp;lt;0.001 vs basal) and AKT phosphorylation. The combined treatment of everolimus and cabergoline induced a significant reduction of both cell proliferation (-34.8 ± 18%, p&amp;lt;0.001 vs basal) and p-AKT/total-AKT ratio (-34.5 ± 14%, p&amp;lt;0.001 vs basal). To test a possible involvement of β-arrestin 2, silencing experiments were performed in MMQ cells. Our data showed that the lack of β-arrestin 2 prevented everolimus and cabergoline co-treatment inhibitory effects on both p-AKT and cells proliferation. In conclusion, these data revealed that cabergoline might overcome the everolimus escape mechanism in NF-PitNETs and tumoral lactotrophs, by inhibiting upstream AKT activation. The co-administration of cabergoline might improve mTOR inhibitors antitumoural activity, paving the way for a potential combined therapy in β-arrestin 2 expressing NF-PitNETs or other PitNETs resistant to conventional treatments. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Evaluating the Efficacy and Safety of Different Pterygium Surgeries: A Review of the Literature.

The search for the “gold standard” in the surgical treatment of pterygium has been ongoing for over two decades. Despite the development of various surgical techniques, recurrence rates range from 6.7% to 88% depending on the method used. This review discusses the latest and most commonly used methods for the surgical removal of pterygium, primarily focusing on efficacy and safety. Moreover, this review includes articles that either evaluated or compared surgical methods and clinical trials for primary and recurrent pterygium. Limited data are available on combined methods as well as on the efficacy of adjuvant treatment. The use of adjuvant intraoperative mitomycin C (MMC) and conjunctival autografting (CAU) are the two most highly recommended options, as they have the lowest rates of postoperative recurrence.

Efficacy of adjuvant treatment for fracture nonunion/delayed union: a network meta-analysis of randomized controlled trials

BackgroundFracture nonunion/delayed union seriously affects physical and mental health and quality of life. The aim of this study was to evaluate the relative efficacy of different adjuvant treatments for nonunion/delayed union by network meta-analysis.MethodsA comprehensive search was performed to identify randomized controlled trials (RCTs) evaluating adjuvant treatment in the management of nonunion/delayed union. A network meta-analysis reporting on healing rate, healing time, and adverse effect (AE) outcomes was conducted to assess and compare different interventions.ResultsThirty studies were included in the analysis. For the healing rate outcome, bone marrow aspirate (BMA) + autologous cancellous bone (ACB) was found to be significantly better than ACB alone (odds ratio: 0.12; 95% confidence interval: 0.03, 0.59). In the ranking results, BMA+ platelet-rich plasma (PRP) (96%), BMA + ACB (90%), and BMA alone (82%) showed relative advantages in the healing rate. Low-intensity pulsed ultrasonography (LIUS) intervention significantly shortened the healing time compared with ACB (SMD: -9.26; 95% CI: − 14.64, − 3.87). LIUS (100%), BMA + PRP (74%), and bone morphogenetic proteins (BMPs) (69%) have relative advantages. Compared with the control, electromagnetic field (EMF) (OR: 13.21; 95% CI: 1.58, 110.40) and extracorporeal shock wave (ESWT) (OR: 4.90; 95% CI: 1.38, 17.43) had a higher AE risk.ConclusionsAmong the current intervention strategies, BMA in combination with PRP and ACB can improve the healing rate of nonunion/delayed union. LIUS can significantly shorten the healing time. EMF and ESWT may have a high risk of AE. However, large-scale, well-designed studies are still needed to confirm the results.Trial registrationRetrospectively registered.

Clinical efficacy of adjuvant treatments for patients with resected biliary tract cancer: a systematic review and network meta-analysis

ObjectiveThis study aimed to determine the benefits of adjuvant therapy in patients with resected biliary tract cancer (BTC) and identify the optimal adjuvant treatment scheme.DesignSystematic review and network meta-analysis.Data sourcesStudies...

Efficacy of Adjuvant Tamsulosin for Improving the Stone-Free Rate after Extracorporeal Shock Wave Lithotripsy in Renal Stones: A Randomized Controlled Trial.

Introduction Extracorporeal shock wave lithotripsy (ESWL) is an effective treatment for urolithiasis. Tamsulosin is capable of causing dilation and facilitating the migration of stones. The aim of this study is to evaluate the efficacy of adjuvant treatment with tamsulosin for improving the stone-free rate after a single session of ESWL in the treatment of kidney stones. Methods This is a randomized, nonplacebo-controlled study with a sample of 60 adults with a single radiopaque kidney stone of 5–20 mm in diameter. After the ESWL session, the patients were divided into two groups. The control group received standard treatment for analgesia consisting of oral diclofenac (75 mg/12 h) as needed. The tamsulosin group received standard treatment for analgesia plus oral tamsulosin (0.4 mg/day) for eight weeks. In both groups, stone-free status was determined using a CT scan eight weeks after ESWL. The protocol of this study was registered with ClinicalTrials.gov, identifier: NCT04819828. Results Only 57 patients completed the study (28 tamsulosin and 29 control). Overall, the average stone diameter was 11.42 ± 4.52 mm. The stone-free rate was 50.88% (29 of 57) overall, 53.57% (15 of 28) for the tamsulosin group, and 48.27% (14 of 29) for the control group (p = 0.680). The estimated relative risk in favor of the tamsulosin group to achieve a stone-free status was 1.11 (95% CI 0.67–1.9). The estimated number needed to treat to achieve a single patient with renal stone-free status after eight weeks of ESWL adjuvant treatment with tamsulosin was 19. Conclusion Our findings suggest that tamsulosin as adjuvant treatment after a single ESWL session is well tolerated and safe, but it does not increase the stone-free rate in patients with a single radiopaque renal stone of 5–20 mm in diameter. Our results may support the use of tamsulosin with ESWL in the case of patients with a single radiopaque renal stone of 11–20 mm in diameter based on an apparent higher stone-free rate and a low rate of complications.

Clinical Efficacy of Adjuvant Treatment of Primary Nephrotic Syndrome in Pediatric Patients with Chinese Medicine.

Objective Current study aimed to investigate the benefits of adjuvant therapy with traditional Chinese medicine on the pediatric primary nephrotic syndrome. Methods A total of 455 patients with PNS admitted to our hospital from January 2010 to January 2019 were divided into the traditional Chinese medicine group (n = 217) and the control group (n = 238). The control group received conventional Western medical treatment, and the traditional Chinese medicine group was treated with traditional Chinese medicine supplemented with Western medical treatment. The differences in remission rate, recurrence rate, and recurrence-free survival between the two groups were evaluated. Results The differences in clinical parameters between the two groups were not statistically significant. Compared with the control group, adjuvant treatment with traditional Chinese medicine increased the clinical remission rate (p=0.037), decreased the relapse rate (p=0.015), prolonged relapse-free survival (p ≤ 0.01), and was an independent protective factor for relapse-free survival in children with PNS (HR = 0.55, 95% CI 0.49–0.63, p ≤ 0.01). In a subgroup analysis of the traditional Chinese medicine formulations, Yuebi Jiazhu Tang, Ganlu Xiaodu Dan, and Yupingfeng granules significantly reduced the risk of recurrence in children (p ≤ 0.01, p ≤ 0.01, p=0.003). Conclusion Adjuvant treatment of pediatric primary nephrotic syndrome with traditional Chinese medicine could benefit the children.

Borderline resectable pancreatic cancer: Certainties and controversies.

Borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) is currently a well-recognized entity, characterized by some specific anatomic, biological and conditional features: It includes patients with a stage of disease intermediate between the resectable and the locally advanced ones. The term BR identifies a tumour with an aggressive biological behaviour, on which a neoadjuvant approach instead of an upfront surgery one should be preferred, in order to obtain a radical resection (R0) and to avoid an early recurrence after surgery. Even if during the last decades several studies on this topic have been published, some aspects of BR-PDAC still represent a matter of debate. The aim of this review is to critically analyse the available literature on this topic, particularly focusing on: The problem of the heterogeneity of definition of BR-PDAC adopted, leading to a misinterpretation of published data; its current management (neoadjuvant vs upfront surgery); which neoadjuvant regimen should be preferably adopted; the problem of radiological restaging and the determination of resectability after neoadjuvant therapy; the post-operative outcomes after surgery; and the role and efficacy of adjuvant treatment for resected patients that already underwent neoadjuvant therapy.

Adjuvant therapy in renal cell carcinoma: is it the right strategy to inhibit VEGF?

Despite several clinical trials have assessed different agents in the adjuvant setting, renal cell carcinoma (RCC) still remains a disease orphan of an effective adjuvant treatment. In fact, systemic therapies targeting angiogenesis that have been observed to be effective in metastatic setting failed to show an improvement in terms of clinical outcomes when used ad adjuvant treatments. In this study, we performed a meta-analysis of 5 randomized clinical trials to assess the impact of tyrosine kinase inhibitors (TKIs) targeting angiogenesis after surgery: ASSURE, S-TRAC, PROTECT, ATLAS, SORCE. Among the 6,531 patients assessed, we confirmed the lack of efficacy of adjuvant treatments in terms of disease-free survival (DFS) (pooled-HR 0.93, 95% CI, 0.84–1.02, P=0.16) and overall survival (OS) (pooled-HR 0.98, 95% CI, 0.88–1.09, P=0.54). To the best of our knowledge, we still ignore why some treatments active in the metastatic setting do not show similar efficacy as adjuvant treatment. Exploring possible reasons of this apparently conflicting results is important as it may offer new insights that should be evaluated in next generation adjuvant trials. Immune checkpoint inhibitors (ICIs) have reported significant results—as monotherapy or in combinations with other anticancer agents—in metastatic setting, and the results of trials evaluating these agents in the adjuvant setting are awaited.

Factores de riesgo y supervivencia en el carcinoma de células de Hürthle. Revisión sistemática y metanálisis

Background: Hurthle cell carcinoma (HCC) of the thyroid gland, which accounts for about 0.4–10% of all differentiated thyroid cancer, is considered differentiated carcinoma with a distinct entity. The treatment of this disease is controversial since there are no prospective randomized controlled trials validating the extent of thyroidectomy and the efficacy of adjuvant treatment with radioactive iodine or radiation therapy.Objective: The aim of this study is to analyze the prognostic factors affecting survival of patients with HCC.Material and methods: We performed an electronic search in MEDLINE, EMBASE, COCHRANE, and LILACS-BIREME databases to find relevant literature regarding risk and prognostic factors affecting survival.Results: Male sex, tumor size > 4 cm, lymph node involvement, extrathyroid extension and distantmetastases were associated with adverse outcome. Total thyroidectomy showed a trend toward higher survival.Conclusions: The management of patients with HCC is still controversial. Large-scale research on multimodal treatments is required. The AACCyC national registry which is opened to all surgeons will provide high quality evidence on the matter. The authors are aware of the strengths and weaknesses of this presentation. This is the first meta-analysis on risk factors and survival of HCC; however, the degree of heterogeneity of the studies was very high for some variables and it was not possible to include in this analysis other risk factors that could affect the prognosis. .

Efficacy and Safety of Endoscopic Resection and Open Surgery for Treating Thyroid Diseases: A Meta-Analysis

To explore the efficacy and safety of endoscopic resection and open surgery for treating thyroid diseases using meta-analysis. Related data in computer retrieval of Cochrane Library, American National Library of Medicine Biomedical Information Retrieval System (Pub Med), Dutch Medicine Abstracts (Embase), China Biomedical Literature Database (CBM), China Academic Journals Full-text Database (CNKI), Chinese Science and Technology Journal Database (VIP), and Western Language Biomedical Journal Literature Database (EMC) from December 2019 to April 2020 were retrieved. Relevant journals and included references were manually searched. Randomized controlled trials regarding the effects of endoscopic thyroid surgery and open thyroid surgery on the immune response of thyroid diseases were included. Two reviewers conducted independent data extraction, quality evaluation and cross-checking according to inclusion and exclusion criteria. RevMan 5.1.4 software was employed. Eight non-randomized controlled retrospective cohort studies were finally included. The curative rate (168/185, 90.81 % vs. 194/383, 50.65 %, p<0.01) was significantly higher in endoscopic resection group and the difference between local recurrence rates (2/366, 0.55 % vs. 83/603, 13.76 %, p<0.01) was significant. There was no significant difference between bleeding rate (1/325, 0.31 % vs. 4/407, 0.98 %, p=0.41). In terms of performing thyroid surgery under endoscopy, the efficacy of adjuvant treatment under endoscopy is significantly better than that of control group and the safety is similar to that of control group. Endoscopic treatment is suitable for treating thyroid diseases. However, the conclusions still need to be verified by multicenter randomized controlled trials with large sample sizes.

Recurrence pattern and outcomes in T4 colon cancer: A single institution analysis.

Patients with T4 colon adenocarcinoma have an increased risk of locoregional and distant recurrence. This study defines the metastatic pattern, predictors of recurrence, and efficacy of adjuvant treatment in T4 colon cancer. A retrospective review was performed of patients with T4 colon adenocarcinoma from May 2005 to November 2015 at a tertiary care hospital. Baseline factors, follow-up, recurrence, and survival were collected and analyzed. Locoregional recurrence (LR) rates for N0, N1, and N2 were 21/85 (24.7%), 14/50 (28%), and 21/46 (45.7%), respectively (P = .014). Multivariate analysis for distant recurrence was significant for positive nodes (hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.1-9.9). Multivariate analysis for LR was significant for the following variables: perforation (HR, 2.7; 95% CI, 1.2-6.2), lymphovascular invasion (HR, 2.7; 95% CI, 1.1-6.7), positive nodes (HR, 2.8; 95% CI, 1.2-6.9), and positive margins (HR, 5.0; 95% CI, 2.1-12.1). Multivariate analysis for overall survival was significant for: signet ring histology (HR, 2.5; 95% CI, 1.2-5.8), positive nodes (HR, 2.3; 95% CI, 1.2-4.4), and positive margin (HR, 2.8; 95% CI, 1.4-5.8). T4 colon adenocarcinoma has a high risk of LR and mortality. Clinical trials utilizing the aforementioned high-risk features may increase the ability to demonstrate beneficial intervention.

Adjuvant Treatments for Advanced Stage, Non-metastatic Upper Tract Urothelial Carcinoma: A Multicenter Study

We assessed the efficacy of adjuvant treatments in patients with peripelvic/periureteral fat-infiltrating (pT3b), nonmetastatic upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy. The multicenter data of 222 patients with pT3bN0-x disease treated with radical nephroureterectomy were analyzed. The effects of adjuvant radiation therapy and chemotherapy on local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and cancer-specific survival (CSS) were evaluated. Adjuvant radiation therapy and chemotherapy were given to 39 (17.6%) and 74 patients (33.3%), respectively. Seventeen patients (7.7%) received concomitant adjuvant radiation therapy and chemotherapy. The median follow-up duration was 34.4months. After adjusting for age, sex, tumor location, multifocality, tumor grade, presence of lymphovascular invasion, surgical margin, execution of node dissection, and other types of concomitant adjuvant treatment (radiation therapy or chemotherapy) through propensity-scored matching, adjuvant radiation therapy significantly reduced the local recurrence (5-year LRFS, 83.9 vs 54.2%; P=.001), distant metastasis (5-year DMFS, 72.1 vs 48.1%; P=.032), and cancer-specific death (5-year CSS, 76.4% vs 55.5%; P=.038) in pT3b UTUC. However, in the same condition, adjuvant chemotherapy did not reduce the local recurrence (5-year LRFS, 69.0% vs 66.2%; P=.786), distant metastasis (5-year DMFS, 65.3% vs 61.1%; P=.436), and cancer-specific death (5-year CSS, 67.9% vs. 67.9%; P=.458) in pT3b UTUC. Our study suggests that adjuvant radiation therapy may be beneficial in patients with T3bN0-x UTUC; however, prospective clinical trials are needed to clarify this issue.

Recurrence pattern and outcomes in T4 colon cancer: A single institution analysis.

706 Background: Patients with T4 colon adenocarcinoma have an increased risk of peritoneal recurrence due to direct seeding malignant cells. It has been theorized that adjuvant chemotherapy may not sterilize the peritoneal surface due to inadequate intraperitoneal concentration. We seek to further define the metastatic pattern, predictors of recurrence, and efficacy of adjuvant treatment in T4 colon cancer. Methods: We reviewed records of 181 adults [median age 71 (22-97)] with T4 N0-3 colon adenocarcinoma at Beaumont Hospital, Michigan from May 2005 –Nov 2015. Baseline factors and data on follow up, metastasis, and survival were collected and analyzed. Results: Overall recurrence rates for N0, N1, and N2 were 27/85 (32%), 17/50 (34%), and 29/46 (63%) (p = 0.001). Locoregional recurrence (LR) rates for N0, N1, and N2 were 21/85 (24.7%), 14/50 (28%), and 21/46 (45.7%) (p = 0.014). Multivariate analysis for distant recurrence was significant only for positive nodes with hazard ratio (HR) 3.3, 95% confidence interval (CI) 1.1-9.9. Multivariate analysis for increased risk of LR was significant for the following variables: perforation (HR 2.7, 95% CI 1.2 – 6.2), lymphovascular invasion (HR 2.7, 95% CI 1.1 – 6.7), positive nodes (HR 2.8, 95% CI 1.2 – 6.9), and positive margins (HR 5.0, 95% CI 2.1 – 12.1). Adjuvant chemotherapy did not decrease risk of LR (HR 0.6, 95% CI 0.3-1.2) or distant recurrence (HR 0.9, 95% CI 0.3-2.8). Multivariate analysis for overall survival revealed the following to be associated with increased risk of mortality: signet ring (HR 2.5, 95% CI 1.2-5.8), positive nodes (HR 2.3, 95% CI 1.2-4.4), positive margin (HR 2.8, 95% CI 1.4-5.8). Adjuvant chemotherapy was not associated with improved survival (HR 0.8, 95% CI 0.4-1.7). Recurrence was strongly associated with colon cancer-specific death with a p &lt; 0.001. Conclusions: Adjuvant chemotherapy is standard of care for most T4 colon cancer patients, however, this data suggests there is no improvement in survival or other significant outcomes. We have identified several risk factors which predict increased risk of LR. This data suggests LR is frequent and not affected by systemic chemotherapy. Prospective trials are needed to reduce the substantial risk of LR in T4 colon cancer.

Efficacy of adjuvant treatment with nebulized lidocaine in improving clinical and pulmonary function parameters of acute asthma attacks: a randomized double-blind clinical trial

Efficient novel medications can facilitate the acute phase of asthma treatment. The aim of this study was to investigate whether nebulized lidocaine as an additional treatment can improve clinical, forced expiratory volume in 1 s (FEV1), and peak expiratory flow rate (PEFR) indexes during an acute asthma attack. A double-blind randomized clinical trial was conducted in 60 adults with possible acute asthma attack who had been referred to the emergency department of our hospital. Patients were randomized into control and treatment groups. The treatment group received nebulized lidocaine 200 mg at 0, 20, 40, and 60 min after arrival + standard treatment with a single dose of oral prednisolone 50 mg at arrival + nebulized albuterol 2.5 mg and nebulized ipratropium bromide 0.5 mg at 0, 20, 40, and 60 min. The control group received only standard treatment. Clinical severity (Borg Dyspnea Scale), FEV1, and PEFR indexes and hemodynamic parameters were recorded at arrival and at 20-min intervals for 60 min after arrival. Mean PEFR and FEV1 increased significantly from baseline in both treatment groups, with no significant between-group differences (BGDs). The BGDs in respiratory rate and hemodynamic parameters (heart rate, systolic and diastolic blood pressure, and oxygen saturation) at 0, 20, 40, and 60 min after arrival were not significant (p > 0.05). Finally, the severity of dyspnea (Borg Dyspnea Scale) did not differ between the two groups at discharge (0.68 vs. 0.76; p = 0.566). The results of this study found no benefit from adding nebulized lidocaine to the standard treatment of asthma attacks. Our data reject any benefits for the efficacy of nebulized lidocaine, at least for short-term use in the acute phase of an asthma attack. Research on the efficacy of nebulized lidocaine during the course of an acute asthma attack is limited, and more research is required to clarify the detailed clinical effects.

Perioperative treatment strategies and current studies to improve gastric cancer outcomes in Japan

In Japan, ACTS-GC demonstrated the beautiful efficacy of adjuvant treatment with 1-year S-1 after D2 dissection in patients with Stage II and III gastric cancers. Based on this result, several attempts have been made according to the stage of the patients. In Stage II, effort has been focused on reducing the toxicity of S-1. Japan Clinical Oncology Group (JCOG) conducted randomized controlled trial (RCT) for evaluating the non-inferiority of 4 course S-1 to standard 8 courses S-1 in Stage II gastric cancer (JCOG1104). On the contrary, more aggressive treatment is preferred for Stage III gastric cancer. One promising candidate is the neo-adjuvant chemotherapy (NAC). JCOG had carried out several phase II studies of NAC for marginally resectable patients and demonstrated substantial tumor responses and improvement in survival. However, solid evidence of survival benefit is lacking until the results of phase III trial (JCOG0501) is disclosed. In addition, to explore the subjects for NAC, accurate preoperative diagnosis is essential. JCOG had performed observational study to confirm the preoperative staging (JCOG1302A) and proceeded to perform RCT with NAC for cT3-4, cN1-3 patients (JCOG1509).