Adjuvant Treatment For Patients Research Articles

Impact of age on the use of adjuvant treatments in patients undergoing surgery for colorectal cancer: patients with stage III colon or stage II/III rectal cancer

BackgroundMany older patients don’t receive appropriate oncological treatment. Our aim was to analyse whether there are age differences in the use of adjuvant chemotherapy and preoperative radiotherapy in patients with colorectal cancer.MethodsA prospective cohort study was conducted in 22 hospitals including 1157 patients with stage III colon or stage II/III rectal cancer who underwent surgery. Primary outcomes were the use of adjuvant chemotherapy for stage III colon cancer and preoperative radiotherapy for stage II/III rectal cancer. Generalised estimating equations were used to adjust for education, living arrangements, area deprivation, comorbidity and clinical tumour characteristics.ResultsIn colon cancer 92% of patients aged under 65 years, 77% of those aged 65 to 80 years and 27% of those aged over 80 years received adjuvant chemotherapy (χ2trends < 0.001). In rectal cancer preoperative radiotherapy was used in 68% of patients aged under 65 years, 60% of those aged 65 to 80 years, and 42% of those aged over 80 years (χ2trends < 0.001). Adjusting by comorbidity level, tumour characteristics and socioeconomic level, the odds ratio of use of chemotherapy compared with those under age 65, was 0.3 (0.1–0.6) and 0.04 (0.02–0.09) for those aged 65 to 80 and those aged over 80, respectively; similarly, the odds ratio of use of preoperative radiotherapy was 0.9 (0.6–1.4) and 0.5 (0.3–0.8) compared with those under 65 years of age.ConclusionsThe probability of older patients with colorectal cancer receiving adjuvant chemotherapy and preoperative radiotherapy is lower than that of younger patients; many of them are not receiving the treatments recommended by clinical practice guidelines. Differences in comorbidity, tumour characteristics, curative resection, and socioeconomic factors do not explain this lower probability of treatment. Research is needed to identify the role of physical and cognitive functional status, doctors’ attitudes, and preferences of patients and their relatives, in the use of adjuvant therapies.

Trends and Predictors of Adjuvant Therapy for Adverse Features Following Radical Prostatectomy: An Analysis From Cancer of the Prostate Strategic Urologic Research Endeavor

OBJECTIVETo determine trends and predictors of adjuvant therapy in patients with adverse features at radical prostatectomy (RP), and to investigate the associations of adjuvant therapy and adverse feature type with survival. METHODSFrom the Cancer of the Prostate Strategic Urologic Research Endeavor registry (1990-2017), 2209 men with adverse features (pT3N0M0 disease and/or positive surgical margins), and 108 men with positive lymph nodes (pN1) at RP were identified. Temporal trends were evaluated, and predictors of adjuvant therapy were assessed with multivariate logistic regression. Kaplan-Meier analysis and competing risks regression were used to test cumulative incidence and risk of all-cause and prostate cancer-specific mortality. RESULTSOf 2209 men with adverse features and pN0 disease, 89 (4.0%), 82 (3.7%), and 30 (1.4%) received adjuvant external beam radiation therapy (ERBT) alone, androgen deprivation therapy (ADT) alone, or combined EBRT and ADT, respectively. Of 108 men with pN1 disease, 54 (50%) received ADT with or without EBRT. Adjuvant treatment for patients with adverse features decreased from 13.3% (1990-1994) to 6% or less (2005-2017, Ptrend <.001). Patients with margin positive pT3a (odds ratio 4.13; 95% confidence interval 2.21-7.73; P<.01) and margin positive pT3b disease (odds ratio 7.09; 95% confidence interval 3.66-1.73; P<.01) had greater odds of receiving adjuvant therapy compared to patients with margin negative pT3a disease. Adverse feature type was associated with prostate cancer-specific mortality in univariate analysis (log-rank P <.01), but not in competing risks regression (P= .06). CONCLUSIONAdjuvant therapy declined for men with adverse features at RP. Providers do not treat all adverse feature types the same way, despite broad treatment recommendations in guidelines.

Clinical and biological impact of miR-18a expression in breast cancer after neoadjuvant chemotherapy.

The analysis of breast cancer residual tumors after neoadjuvant chemotherapy (nCT) may be useful for identifying new biomarkers. MicroRNAs are known to be involved in oncogenic pathways and treatment resistance of breast cancer. Our aim was to determine the role of miR-18a, a member of the miR-17-92a cluster, in breast cancer behavior and outcome after nCT. Pre- and post-nCT tumor miR-18a expression was retrospectively assessed by qRT-PCR in 121 patients treated with nCT and was correlated with survival outcomes and with clinical and pathological characteristics. Breast cancer-derived MCF-7 and MDA-MB-231 cell lines were transfected with miR-18a and anti-miR-18a to evaluate the biological effects of this molecule. In addition, whole-transcriptome expression analysis was performed. High miR-18a expression in post-nCT residual tumors was found to be associated with a significantly worse overall survival [hazard ratio (HR): 2.80, 95% confidence interval (CI): 1.01-7.76] and a strong trend towards a poorer disease-free survival (HR: 2.44, 95% CI: 0.99-5.02) compared to low miR-18a expressing post-nCT residual tumors. Clinical and experimental data were found to be in conformity with the proliferative effects of miR-18a, which showed a significant correlation with Ki67 and MYBL2 expression, both in pre- and post-nCT tumors and in public databases. In vitro analysis of the role of miR-18a in breast cancer-derived cell lines showed that a high expression of miR-18a was associated with a low expression of the estrogen receptor (ER), a decreased sensitivity to tamoxifen and an enrichment in luminal B and endocrine resistance gene expression signatures. From our data we conclude that post-nCT miR-18a expression in breast cancer serves as a negative prognostic marker, especially in luminal tumors. Clinical, in vitro and in silico data support the role of miR-18a in breast cancer cell proliferation and endocrine resistance and suggest its potential utility as a biomarker for additional adjuvant treatment in patients without a pathologic complete response to neoadjuvant therapy.

NATALEE: Phase III study of ribociclib (RIBO) + endocrine therapy (ET) as adjuvant treatment in hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) early breast cancer (EBC).

TPS597 Background: RIBO is a selective inhibitor of CDK4/6 with demonstrated efficacy and is well tolerated when combined with ET in pre-/peri- and postmenopausal women with HR+, HER2– advanced breast cancer. Given these findings and considering the role of CDK4/6–Rb–E2F pathway dysregulation in ET resistance, there is a rationale for evaluating whether RIBO + ET prevents, or delays acquired resistance to ET in the adjuvant setting, to improve invasive disease-free survival (iDFS). Methods: The phase 3 multicenter, randomized, open-label NATALEE trial will evaluate the efficacy and safety of RIBO + ET as adjuvant treatment in patients with HR+, HER2– EBC. Eligible women (any menopausal status) and men aged ≥ 18 years will be randomized to RIBO 400 mg/day (3 weeks on/1 week off) + ET or ET alone. In both arms, ET will comprise daily continuous letrozole 2.5 mg/day or anastrozole 1 mg/day; men and premenopausal women will also receive goserelin 3.6 mg once every 28 days. Treatment with RIBO will last 36 months whereas treatment with ET (in both arms) will last 60 months. Patients must have had American Joint Committee on Cancer (8th ed.) Anatomic Stage II (either N0 with grade 2-3 and/or Ki67 ≥ 20% or N1) or III EBC, with an initial diagnosis ≤ 18 months prior to randomization, and completed chemotherapy and radiotherapy (if indicated). Patients receiving standard (neo)adjuvant ET are eligible only if this treatment was initiated within 12 months of randomization. Key exclusion criteria include previous CDK4/6 inhibitor treatment and clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality. The primary endpoint is iDFS using STEEP (Standardized Definitions for Efficacy End Points) criteria as assessed by the investigator; secondary endpoints include recurrence-free survival, distant DFS, overall survival, patient-reported outcomes, and RIBO pharmacokinetics. Safety and tolerability will also be evaluated. Estimated enrollment is 4000 patients from 425 sites in 21 countries. Recruitment is ongoing. Clinical trial information: NCT03701334.

ALINA: A phase III study of alectinib versus chemotherapy as adjuvant therapy in patients with stage IB–IIIA anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC).

TPS8569 Background: Patients with early-stage NSCLC (stage IA–IIIA) account for ~40% of cases at diagnosis; despite surgery, 5-year survival rates are low. Platinum-based adjuvant chemotherapy is the standard of care (SoC) for stage II–IIIA disease. Although patients with stage IA NSCLC do not benefit from adjuvant chemotherapy, patients with stage IB disease and large tumors (≥4cm) do. Adjuvant chemotherapy produces a 4–5% increase in 5-year survival rates, leaving significant unmet need for improved treatments. Approximately 5% of patients with NSCLC harbor an oncogenic fusion of the ALK gene. Treatment of advanced ALK+ NSCLC with ALK inhibitors improves efficacy and safety compared with chemotherapy. Alectinib, a potent ALK inhibitor, is the SoC first-line treatment for advanced ALK+ NSCLC. The ongoing ALINA trial will compare alectinib versus chemotherapy as adjuvant treatment for patients with stage IB–IIIA ALK+ NSCLC. Methods: ALINA is a randomized, multicenter, open-label phase III study investigating the efficacy and safety of adjuvant alectinib versus chemotherapy in ALK+ NSCLC (confirmed by an FDA-approved and CE-marked test). Adult patients (≥18 years) with completely resected stage IB (tumors ≥4cm) to IIIA disease and ECOG PS 0–1 are eligible for inclusion. Patients (N=255) from ~170 centers across ~30 countries will be randomized 1:1 to receive twice-daily alectinib 600mg for 24 months or four 21-day cycles of platinum-based chemotherapy (cisplatin 75mg/m2 [day 1] plus vinorelbine 25mg/m2 [days 1 and 8] or gemcitabine 1250mg/m2 [days 1 and 8] or pemetrexed 500mg/m2 [day 1]) according to local prescribing information. Stratification factors are disease stage (stage IB [≥4cm] vs stage II vs stage IIIA) and race (Asian vs non-Asian). Treatment will continue until planned completion, disease recurrence, unacceptable toxicity, withdrawal of consent, or death, whichever occurs first. The primary endpoint is disease-free survival per investigator; secondary endpoints are overall survival, safety, and pharmacokinetics. Clinical trial information: NCT03456076.

KEYNOTE-756: Randomized, double-blind, phase 3 study of pembrolizumab vs placebo combined with neoadjuvant chemotherapy and adjuvant endocrine therapy for high-risk, early-stage estrogen receptor–positive, human epidermal growth factor receptor 2–negative (ER+/HER2−) breast cancer.

TPS601 Background: Although ER+/HER2− breast cancer (BC) has better overall prognosis than other subtypes, a high-risk subpopulation is characterized by high-grade tumors, decreased sensitivity to endocrine therapy (ET), higher responsiveness to chemotherapy (CT), and worse prognosis. Based on prior studies, increased pathological complete response (pCR) rates after neoadjuvant CT may have a substantial impact for patients with high-risk, early-stage HR+/HER2− BC. KEYNOTE-756 (ClinicalTrials.gov, NCT03725059) is a global, randomized, double-blind, phase 3 study of pembrolizumab (vs placebo) + CT as neoadjuvant treatment followed by pembrolizumab (vs placebo) + ET as adjuvant treatment for patients with high-risk, early-stage ER+/HER2− BC. Methods: Patients with T1c-2 cN1-2 (tumor size ≥2 cm) or T3-4 cN0-2 grade 3, invasive, ductal ER+/HER2− BC will be stratified by lymph node involvement (positive vs negative), tumor PD-L1 status (positive [CPS≥1] vs negative [CPS &lt; 1]), ER positivity (ER+ ≥10% vs ER+ &lt; 10%), and anthracycline dosing schedule (every 3 weeks [Q3W] vs Q2W), then randomized 1:1 to neoadjuvant treatment with pembrolizumab 200 mg Q3W or placebo combined with paclitaxel (80 mg/m2 Q1W) for 4 cycles followed by doxorubicin (60 mg/m2) or epirubicin (100 mg/m2), each with cyclophosphamide (600 mg/m2) Q2/3W for 4 cycles. After definitive surgery (± radiation therapy, as indicated), patients will receive adjuvant treatment of pembrolizumab (200 mg Q3W) or placebo for 9 more administrations combined with ET, which can be given for up to 10 years. There will be no crossover between treatment arms when moving from neoadjuvant to adjuvant treatment. Dual primary endpoints are pCR rate (ypT0/Tis ypN0) and event-free survival (EFS). Secondary endpoints include ypT0/Tis and ypT0 ypN0 pCR rates in all patients and all 3 pCR definitions in those with PD-L1+ tumors, EFS in patients with PD-L1+ tumors, overall survival, safety, and health-related quality of life. Interim analyses are planned. Enrollment is currently ongoing. Clinical trial information: NCT03725059.

Comparative efficacy of neoadjuvant to adjuvant chemotherapy for the treatment of early-stage HER2 negative breast cancer: A population-based analysis.

e12100 Background: The use of neoadjuvant treatment has increased over the past decade due to its ability to assess tumour sensitivity to systemic treatment in vivo, and to downstage women for increased breast conserving surgery. Recent studies have stratified patients with residual disease to receive additional treatment, which has resulted in meaningful improvements in survival. However, meta-analysis data suggest similar long-term outcomes for patients treated with neoadjuvant chemotherapy (NACT) compared to adjuvant chemotherapy (ACT) in historical randomized trials. The comparative efficacy in a real-world setting utilizing modern chemotherapy regimens is unknown. Methods: A retrospective review of the BC Cancer Breast Cancer Outcomes Unit (BCOU) was performed to identify patients with stage I-III HER-2 negative breast cancer treated with chemotherapy at the BC Cancer Agency from 2005-2010. Patients were then divided into 2 groups: those who received neoadjuvant chemotherapy (NACT) and those who received adjuvant chemotherapy (ACT). A matched analysis (age, stage, subtype) for patients treated with NACT vs ACT (matched 1:3) was then performed using a propensity scoring method to compare distant disease-free survival (DDFS), breast cancer specific survival (BCSS) and overall survival (OS). No patients received adjuvant chemotherapy for residual disease after NACT. Results: A total of 656 patients met the inclusion criteria, consisting of 164 NACT and 492 ACT cases. Median age was 49 years (37-68) in the NACT group vs 49 (37-65) in the ACT group (p = 0.71). The majority had stage 3 disease, 64% in both groups (p = 1.0). Most were hormone receptor positive (HR+), 67.1% vs 70.7% in the NACT vs ACT groups, respectively (p = 0.41). 5-year DDFS was 75% with NACT (95%CI 67, 82) and 77% with ACT (95%CI 72, 81), p = 0.87. 5-year OS for patients treated with NACT was 77% (95%CI 71, 84) and 80% (95%CI 75, 85) for patients treated with ACT, p = 0.33. 5-year BCSS was 80% with NACT (95% CI 70, 86) and 82% (95%CI 77, 86) with ACT, p = 0.75. Multivariate analysis for tumour size, nodal involvement and subtype are ongoing. Conclusions: The use of NACT compared to ACT in a population-based setting did not result in significant differences in DDFS, OS or BCSS. Acknowledging the comparative efficacy of these approaches will be informative to determine if the addition of subsequent adjuvant treatment for patients with residual disease after NACT will lead to differential benefits in a population-based setting.

The effect of Chinese herbal formula as adjuvant treatment for patients with ACS: study protocol for a prospective cohort study

The effect of Chinese herbal formula as adjuvant treatment for patients with ACS: study protocol for a prospective cohort study

Photodynamic therapy for R1 lung cancer resections

Theobjectivewas to evaluate the effectiveness of endobronchial photodynamic therapy (PDT) for preventing a non-small cell lung cancer (NSCLC) relapse after R1 resection with positive bronchial resection margins.Material and methods.This study included 17 patients. The planned morphological diagnostics revealed the presence of tumor cell complexes at the bronchial resection margins in 5 (29 %) patients (cancer in situ – 2, invasive cancer – 3), in peribronchial tissues – in 5 (29 %) patients, in lymphatic vessels at the resection margins – in 7 (41 %) patients.Results.All patients underwent one session of endobronchial PDT as an adjuvant treatment. No complications of PDT were noted. The five-year observation revealed a relapse at the bronchial stump area in 1 patient only (6 %). 16 (94 %) patients lived for 1 year, 12 (71 %) patients – for 5 years. Long-term results were significantly worse in patients with tumor complexes in lymphatic vessels at the bronchial resection margins (5-year survival rate – 29 %, p=0.04), with pN2 (0 %, p=0.01), lung adenocarcinoma (20 %, p=0.03).Conclusion.The use of endobronchial PDT as an adjuvant treatment for patients with NSCLC after R1 resection with positive bronchial resection margins is simple, safe and characterized by good immediate and long-term results.

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.

Abstract OT3-04-03: KEYNOTE-756: A randomized, double-blind, phase III study of pembrolizumab versus placebo in combination with neoadjuvant chemotherapy and adjuvant endocrine therapy for high-risk early-stage ER+/HER2– breast cancer

Abstract Background:Although ER+/HER2– breast cancer has a better overall prognosis than other breast cancer subtypes, there is a high-risk subpopulation characterized by high-grade tumors and decreased sensitivity to endocrine therapy, higher responsiveness to chemotherapy and worse prognosis. A large meta-analysis of prospective studies focusing on neoadjuvant chemotherapy (NAC) for treatment of stage I-III breast cancer demonstrated that increased pathologic complete response (pCR) rates at surgery were associated with improved survival. This correlation was observed across triple-negative breast cancer (TNBC), HER2+ breast cancer, and high-grade HR+/HER2- breast cancer. Specifically, patients with a pCR after NAC had a 5-year event-free survival (EFS) rate of 90%, whereas patients who did not achieve a pCR had a 5-year EFS rate of 60%.Therefore, increasing pCR rates after NAC may have a substantial impact for patients with high-risk early-stage HR+/HER2– breast cancer. KEYNOTE-756 is a global, randomized, double-blind, phase III study of pembrolizumab (vs placebo) + chemotherapy as neoadjuvant treatment, followed by pembrolizumab (vs placebo) plus endocrine therapy as adjuvant treatment for patients with high-risk, early-stage ER+/HER2– breast cancer. Methods: Patients with T1c-2 cN1-2 or T3-4 cN0-2 grade 3 or grade 2 with Ki-67 ≥30%, invasive, ductal ER+/HER2– breast cancerwill be stratified by lymph node involvement (positive vs negative), tumor PD-L1 status (positive vs negative), ER positivity (≥10% vs &amp;lt;10%), and anthracycline dosing schedule (Q3W vs Q2W), and then randomized 1:1 to receive neoadjuvant treatment with pembrolizumab 200 mg Q3W or placebo in combination with paclitaxel (80 mg/m2 QW) for 4 cycles followed by (doxorubicin [60 mg/m2] or epirubicin [100 mg/m2]) plus cyclophosphamide (600 mg/m2) Q2/3W for another 4 cycles. After definitive surgery (± radiation therapy, as indicated), patients will receive adjuvant treatment with pembrolizumab (200 mg Q3W) or placebo for 9 additional administrations, in combination with endocrine therapy, which can be given for up to 10 years. Co-primary end points are pCR rate and EFS. Secondary end points are safety and overall survival. The global study will open in North America and Latin America, Europe, and Asia Pacific in the second half of 2018. Citation Format: Cardoso F, Bardia A, Andre F, Cescon DW, McArthur H, Telli M, Loi S, Cortés J, Schmid P, Harbeck N, Denkert C, Jackisch C, Jia L, Tryfonidis K, Karantza V. KEYNOTE-756: A randomized, double-blind, phase III study of pembrolizumab versus placebo in combination with neoadjuvant chemotherapy and adjuvant endocrine therapy for high-risk early-stage ER+/HER2– breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT3-04-03.

Melatonin attenuates TNF-α and IL-1β expression in synovial fibroblasts and diminishes cartilage degradation: Implications for the treatment of rheumatoid arthritis.

The hormone melatonin has many properties, including antioxidant, anti-inflammatory, and immunomodulatory effects. Melatonin has been demonstrated to be beneficial in several inflammatory autoimmune diseases, but its effects in rheumatoid arthritis (RA) remain controversial. We sought to determine how melatonin regulates inflammation in RA. We found that melatonin dose-dependently inhibits tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β expression through the PI3K/AKT, ERK, and NF-κB signaling pathways. We also identified that melatonin inhibits TNF-α and IL-1β production by upregulating miR-3150a-3p expression. Synovial tissue specimens from RA patients and culture of human rheumatoid fibroblast-like synoviocytes confirmed that the MT1 receptor is needed for the anti-inflammatory activities of melatonin. Importantly, melatonin also significantly reduced paw swelling, cartilage degradation, and bone erosion in the collagen-induced arthritis mouse model. Our results indicate that melatonin ameliorates RA by inhibiting TNF-α and IL-1β production through downregulation of the PI3K/AKT, ERK, NF-κB signaling pathways, as well as miR-3150a-3p overexpression. The role of melatonin as an adjuvant treatment in patients with RA deserves further clinical studies.

Routine use of commercial antibiotic-loaded bone cement in primary total joint arthroplasty: a critical analysis of the current evidence.

Antibiotic-loaded cement (ABLC) has been widely utilized as an adjuvant treatment for patients with periprosthetic joint infection (PJI) but has also evolved to play a prophylactic role against infection in primary total joint arthroplasties (TJA). Nevertheless, there is currently a paucity of studies that systematically investigated this concept. This review aimed at answering the following questions: (I) Can routine use of ABLC help reduce the current infection rates in primary TJA? (II) What are the risks associated with this approach? And (III) can routine use be justified in primary TJA from an economic standpoint? Multiple databases were queried including PubMed, EMBASE, EBSCO Host, and SCOPUS. Studies published between January 1, 1990 and March 31, 2018 were reviewed. Inclusion criteria were studies reporting: (I) clinical outcomes of routine use of ABLC in primary hip and knee arthroplasty with 2-year minimum follow-up, (II) complications related to the use of ABLC, (III) cost of using ABLC. The final analysis included 24 studies. Data from multiple studies demonstrate contradictory results for infection rates when ABLC is used in all primary procedures with a majority of studies showing similar infection rates between ABLC and plain cement. The main concerns associated with routine use of ABLC are negative effects on the mechanical stability of cement, possible systemic and local toxicity of the absorbed antibiotic, and development of resistant bacterial strains. However, current literature has not clinically validated these concerns. Lastly, with an estimated increase in 117 million dollars with the routine use of ABLC in only 50% of TJAs performed each year, it is difficult to justify the use of ABLC without clear superiority in reducing infection. The use of ABLC has undeniably changed the way orthopaedic surgeons deal with PJI today. However, the large-scale, prophylactic use of ABLC in primary TJAs requires further research and justification.

Validity and Reliability of the Decision Regret Scale in Cancer Patients Receiving Adjuvant Chemotherapy

ObjectivesDecisional regret is an indicator of satisfaction with the treatment decision and can help to identify those patients who need more support and evaluate the efficacy of decision support interventions. The objectives of this study are, 1) to evaluate the psychometric properties of the Decision Regret Scale and 2) to analyze the moderating effect of psychological distress on functional status and regret in patients with cancer following adjuvancy. MethodsA prospective, multicenter cohort of 403 patients who completed the Decision Regret Scale (DRS), Health-Related Quality of Life (EORTC QLQ-C30), and Brief Symptom Inventory (BSI). The evaluation was conducted six months after receiving adjuvant treatment in patients with resected cancer. ResultsAfter treatment, most participants (51.9%) experienced no decision regret; 33.7% felt mild regret, and 14.4% exhibited high levels of regret. The Spanish version of the DRS demonstrated satisfactory properties: it had a strong, clear unidimensional factorial structure with substantial loadings. Decisional regret was related with lower scores on functional, symptom, and quality of life scales, and higher levels of psychological distress (all P = 0.001). Psychological distress was found to have a moderating effect on the relationship between functional state and decision regret. ConclusionsThe Spanish version of the DRS is a reliable, valid tool to evaluate regret and post-decisional quality in clinical practice and further highlights the potential clinical implications of psychological distress for the relation between physical status and regret.

Pilot study of bevacizumab in combination with docetaxel and cyclophosphamide as adjuvant treatment for patients with early stage HER-2 negative breast cancer, including analysis of candidate circulating markers of cardiac toxicity: ICORG 08-10 trial.

Background:Combining bevacizumab and chemotherapy produced superior response rates compared with chemotherapy alone in metastatic breast cancer. As bevacizumab may cause hypertension (HTN) and increase the risk of cardiac failure, we performed a pilot study to evaluate the feasibility and toxicity of a non-anthracycline-containing combination of docetaxel with cyclophosphamide and bevacizumab in early stage breast cancer patients.Methods:Treatment consisted of four 3-weekly cycles of docetaxel and cyclophosphamide (75/600 mg/m2). Bevacizumab was administered 15 mg/kg intravenously on day 1, and then every 3 weeks to a total of 18 cycles of treatment. Serum biomarker concentrations of vascular endothelial growth factor (VEGF), cardiac troponin-I (cTnI), myeloperoxidase (MPO), and placental growth factor (PlGF) were quantified using enzyme-linked immunosorbent assay (ELISA) in 62 patients at baseline and whilst on treatment to determine their utility as biomarkers of cardiotoxicity, indicated by left ventricular ejection fraction (LVEF).Results:A total of 106 patients were accrued in nine sites. Median follow up was 65 months (1–72 months). Seventeen protocol-defined relapse events were observed, accounting for an overall disease-free survival (DFS) rate of 84%. The DFS rates for hormone receptor positive (HR+) and triple-negative (TN) patients were 95% versus 43%, respectively. The median time to relapse was 25 (12–54) months in TN patients versus 38 (22–71) months in HR+ patients. There have been 13 deaths related to breast cancer . The overall survival (OS) rate was 88%. The 5-year OS rate in HR+ versus TN was 95% versus 57%. None of the measured biomarkers predicted the development of cardiotoxicity.Conclusions:We observed a low relapse rate in node-positive, HR+ patients; however, results in TN breast cancer were less encouraging. Given the negative results of three large phase III trials, it is unlikely that this approach will be investigated further.Trial RegistrationClinicalTrials.gov Identifier: NCT00911716.

The Usefulness of Postoperative Direct Voice Therapy in Vocal Polyps

Background and Objectives Previous studies have suggested the usefulness and importance of postoperative voice therapy, for which there are indirect and direct methods. The aim of this study was to evaluate the efficacy of treatment according to different voice therapy methods. Subjects and Method Patients with vocal polyp were divided into three groups. Group 1 received direct voice therapy after phonomicrosurgery and Group 2 indirect voice therapy after phonomicrosurgery. Group 3 did not receive any voice therapy. Results Perceptual, acoustic, aerodynamic voice outcome parameters differed significantly between pre and post-operative treatments. In almost all of the voice analysis, Group 1, who underwent direct voice therapy, improved more significantly compared with Group 2 and 3. Conclusion Postoperative voice therapy following phonomicrosurgery may be an effective adjuvant treatment in patients with vocal polyps. In particular, direct voice therapy can be effective for improving postoperative voice outcome. Key words: Phonomicrosurgery ㆍ Vocal polyp ㆍ Voice therapy

Locomotor and anti-immobility effects of buprenorphine in combination with the opioid receptor modulator samidorphan in rats

Modulation of the opioid system has re-emerged as a potential therapeutic avenue for treating depression, with efficacy of a fixed-dose combination of buprenorphine (BUP), a partial μ-opioid receptor (MOR) agonist and κ-opioid receptor (KOR) antagonist, and samidorphan (SAM), a potent MOR antagonist, as an adjuvant treatment in patients with major depressive disorder (MDD). To advance understanding of the mechanism of action underlying this combination, we examined BUP, SAM and their combination in a series of rat behavioural assays. We examined effects on locomotor activity in Sprague Dawley (SD) rats over an extended period of time in a home-cage tracking system, and behavioural despair (immobility) in the forced swim test (FST), a commonly-used test to study antidepressants, in SD and Wistar-Kyoto (WKY) rats. Strain differences in opioid receptor and prepropeptide mRNA expression in the brain (prefrontal cortex, amygdala, hippocampus and striatum) were examined using qRT-PCR. BUP produced locomotor hyperactivity in SD rats from 2 to 6 h following administration, which was attenuated by SAM. In SD rats, a low, but not a high, dose of SAM in combination with BUP counteracted swim-stress induced immobility. This effect was not seen with BUP alone. In contrast, BUP alone reduced immobility in WKY rats, and this effect was enhanced by a low, but not high, dose of SAM. In WKY rats, MOR mRNA expression was higher in the hippocampus and lower in the striatum vs. SD rats. KOR mRNA expression was higher in the amygdala and nociceptin receptor (NOP) mRNA expression was lower in the hippocampus vs. SD rats. Differences in opioid receptor expression may account for the differential behavioural profile of WKY and SD rats. In summary, administration of BUP, a MOR receptor agonist together with a MOR opioid-receptor antagonist, SAM, reduces behavioural despair in animal models traditionally used to study effects of antidepressants.

National patterns of care and cancer-specific outcomes of adjuvant treatment in patients with serous and clear cell endometrial carcinoma

ObjectivesTo investigate outcomes of adjuvant therapy for serous and clear cell endometrial carcinoma, as prior studies are limited by sample size and/or patient heterogeneity. National guidelines permit substantial variations in treatment, suggesting the need for additional data. MethodsPatients with FIGO stages I–III serous or clear cell uterine carcinoma who underwent at least total hysterectomy were identified in SEER-Medicare. Adjuvant external beam radiation, brachytherapy, and chemotherapy were determined using SEER fields and Medicare claims. The primary outcome was death from endometrial cancer (cancer-specific mortality [CSM]) evaluated using Gray's test (univariable analysis, UVA) and Fine-Gray regression (multivariable analysis, MVA). ResultsA total of 1789 patients (1437 serous, 352 clear cell) were identified. In stages I–II patients (n = 1188), brachytherapy was significant for survival in UVA (P = 0.03) and MVA (P = 0.02). Additionally, in the subset with serous histology (n = 947), chemotherapy was also significant in UVA (P = 0.002) and approached significance in MVA (P = 0.05). The 4-year CSM for stages I–II serous cancers was 25% without brachytherapy or chemotherapy, 15% with one, and 9% with both (P ≤ 0.05 for all pairwise comparisons). In stage III patients (n = 601), chemotherapy was significant in UVA (P = 0.002) and MVA (P = 0.006). Most (81%) patients underwent lymph node dissection, which predicted lower CSM in stage III (P = 0.001) but not stages I–II patients. ConclusionsOur results suggest brachytherapy benefits stages I–II serous/clear cell cancers, chemotherapy benefits stage III serous/clear cell cancers, and both chemotherapy and brachytherapy benefit stages I–II serous cancers.

Avaliação histopatológica dos órgãos de camundongos com carcinoma de ehrlich tratados com cisplatina, acupuntura e euphorbia tirucalli l.

Introdução: O câncer é uma das maiores causas de morte do mundo sendo considerado um problema de saúde pública. Objetivo: Objetivou-se realizar a avaliação histopatológica de órgãos de camundongos com carcinoma de Erhlich tratados com cisplatina, acupuntura e a planta Euphorbia tirucalli L. Metodologia: Utilizou-se 25 camundongos, fêmeas, com 60 dias de idade, 25 e 35 g de peso corpóreo sendo divididos em Grupo 1 – Controle negativo - 1ml de Soro Fisiológico 0,9% (VO); Grupo 2 – Controle positivo - 2,5mg/kg de Cisplatina (VO); Grupo 3 - Pré-tratamento com acupuntura + 2mg/kg da Euphorbia tirucalli (VO); Grupo 4 – Acupuntura; Grupo 5 - Acupuntura + 2mg/kg Euphorbia tirucalli (VO). Inoculou-se células do carcinoma em todos os animais e durante 8 dias foi realizado os protocolos terapêuticos. No nono dia os camundongos foram pesados, eutanasiados por deslocamento cervical, necropsiados para avaliação macroscópica e histológica dos órgãos e do tumor. Os acupontos utilizados foram B10, VB30 e F3. Resultados: Houve variação significativa no peso dos órgãos (Rins, Baço, Fígado) e do Tumor. As principais alterações histopatológicas foram pneumonia, hepatite, necrose hepática, degeneração gordurosa e hiperplasia da polpa branca do baço. Conclusão: A cisplatina demonstrou ser o tratamento mais eficaz em camundongos com carcinoma de Erhlich quanto a redução do tumor. A dose utilizada na pesquisa do látex da Euphorbia tirucalli L. demonstrou ser hepatotóxica, no entanto os tratamentos com acupuntura e a planta proporcionaram uma resposta imunológica. Assim, sugere-se a associação da acupuntura e da Euphorbia tirucalli como tratamentos coadjuvantes em pacientes com carcinoma.Palavras-chaves: Câncer. Etnobotânica. Fitoterapia. Medicina Tradicional Chinesa.

Surgery in nontuberculous mycobacteria pulmonary disease.

Medical treatment of pulmonary nontuberculous mycobacteria (NTM) disease has highly variable outcomes. Despite the use of multiple antibiotics, sputum clearance is often difficult to achieve, especially in cases with macrolide resistant NTM infection. Immunocompromised patients and those with structural lung disease are at increased risk, although occurrence in immunocompetent patients without structural lung disease is well recognised. Most pulmonary NTM disease involves Mycobacterium avium complex (MAC), but with enhanced identification multiple species have now been recognised as opportunistic pathogens. The observed increase in NTM disease, especially infection with multidrug-resistant Mycobacterium abscessus complex, is probably multifactorial. Surgery has been used as adjuvant treatment in patients with 1) focal disease that can be removed or 2) bothersome symptoms despite medical treatment that can be ameliorated. Early post-surgical mortality is low, but long-term morbidity and mortality are highly dependent on the degree of lung involvement and the residual lung function, the potency of medical treatment and the type of surgical intervention. In conjunction with antibiotic therapy, reported post-surgical sputum clearance was excellent, although publication bias should be considered. Bronchopleural fistulae were problematic, especially in pneumonectomy cases. Study results support the use of minimal resection surgery, in a carefully selected subgroup of patients with focal disease or persistent symptoms.Educational aimsTo critically review the literature describing the use of surgery in the treatment of pulmonary disease caused by nontuberculous mycobacteria (NTM).To assess the outcomes and complications observed with different surgical approaches used in the treatment of pulmonary NTM disease.