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Background & Aims: Whether higher liver transplant (LT) waitlist mortality in patients with poor functional status (FS) is mediated by higher prevalence of cirrhosis complications is not clear. We aim to evaluate the impact of FS on risk of hepatic encephalopathy (HE), ascites, and spontaneous bacterial peritonitis (SBP) among adults listed for LT., Methods: Using 2005-2018 United Network for Organ Sharing LT data, we retrospectively evaluated the impact of FS on prevalence of ascites, HE, and SBP among adults listed for LT using Karnofsky Performance Status Score categories (KPSS-1: FS 80-100%, KPSS-2: 60-70%, KPSS-3: 40-50%, KPSS-4: 10-30%), stratified by underlying liver disease etiology. Between-group comparisons used chi-squared methods and adjusted multivariate logistic regression., Results: Among 100,618 adults listed for LT (68.8% male, 72.4% non-Hispanic white) 35.2% were KPSS-1, 36.6% KPSS-2, 15.7% KPSS-3, and 12.6% KPSS-4 at time of LT waitlist registration. Patients with worse FS were significantly more likely to have ascites, HE, and SBP at time of waitlist registration (KPSS-1 vs. KPSS-4: ascites, 66% vs. 93%; HE, 81% vs. 49%; SBP, 4% vs. 16%, p < 0.001 for all). On multivariate regression, compared with patients with KPSS-1, those with KPSS-4 had significantly higher odds of ascites (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.37-1.62, p < 0.01), HE (OR: 1.69, 95% CI: 1.59-1.80, p < 0.01), and SBP (OR: 2.17, 95% CI: 1.98-2.38, p < 0.01), which was observed across all liver disease etiologies., Conclusion: Worse FS is associated with higher odds of cirrhosis complications including ascites, HE, and SBP, which was observed across all liver disease etiologies., Competing Interests: The authors have nothing to declare., (© 2020 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Liver transplantation (LT) is a game changer in cirrhosis. Poor muscle mass defined as sarcopenia may potentially upset the LT scoreboard., Aim: To assess the prevalence and impact of sarcopenia on the intraoperative and early postoperative outcomes in Indian patients undergoing LT., Methods: Pre LT, single-slice routine computed tomography images at L3 vertebra of 115 LT recipients were analyzed, to obtain cross-sectional area of six skeletal muscles normalized for height in m 2 - skeletal muscle index (SMI; cm 2 /m 2 ). SMI< 52.4 in males and <38.5 in females was called sarcopenia. The intraoperative, postoperative outcome parameters and 90-day mortality were compared between sarcopenics and nonsarcopenics., Results: Sarcopenia was found in 47.8% of patients [M (90.4%); age, 46.3 ± 10; BMI, 24.5 ± 4.3 kg/m2; child A:B:C = 1%:22%:77%; MELD, 20.6 ± 6.3; etiology alcohol: nonalchohol = 53%:47%; Charlson Comorbidity Index (CCI) > 3:≤3 = 56.5%:43.5%]. Sarcopenics vs. Nonsarcopenics; early postoperative complications: [sepsis, 49(89%) vs. 33(55%), P  = 0.001; neurologic complications, 16(29.6%) vs. 5(8.8%), P  = 0.040; Clavien-Dindo Classification ≥3-24 (43.6%):15 (25.4%), P  = 0.041; ancillary parameters (days), duration of ventilation [median (range)] 1.5(1-3) vs. 1 (1-2), P  = 0.021; intensive care unit (ICU) stay 12 (8-16) vs. 10 (8-12), P  = 0.024; time to ambulation 9 (7-11) vs. 6 (5-7), P  = 0.001; drain removal 18.7 ± 7.3 vs. 14.4 ± 6.2, P  = 0.001; need for tracheostomy 5 (9%) vs. 0 (%), P  = 0.017; preoperative prevalence of acute kidney injury, comorbidities and requirement for dialysis, intraoperative blood loss & inotropic support were significantly higher in sarcopenics. Ninety-day mortality was comparable between sarcopenics 5 (9.09%) and nonsarcopenics 4 (6.6%) P  = 0.63. SMI (OR: 0.83; 95% CI: 0.71-0.97, P  = 0.016; Acute on chronic liver failure (ACLF) presentation 12.5 (1.65-95.2), P  = 0.015 and intraoperative blood loss 3.74 (0.96-14.6), P  = 0.046 were predictors of 90-day mortality., Conclusion: Almost 50% of LT recipients had sarcopenia, who had a higher incidence of postoperative sepsis, neurological complications, longer ICU stay and ventilatory support. Low SMI, ACLF presentation, and intraoperative blood loss were the independent predictors of early mortality., (© 2019 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Our previous study indicated that intravenous vitamin C (IVC) treatment concurrent with modulated electrohyperthermia (mEHT) was safe and improved the quality of life (QoL) of non-small-cell lung cancer (NSCLC) patients. The aim of this trial was to further verify the efficacy of the above combination therapy in previously treated patients with refractory advanced (stage IIIb or IV) NSCLC. A total of 97 patients were randomized to receive IVC and mEHT plus best supportive care (BSC) (n = 49 in the active arm, receiving 1 g/kg * d IVC concurrently with mEHT, three times a week for 25 treatments in total) or BSC alone (n = 48 in the control arm). After a median follow-up of 24 months, progression-free survival (PFS) and overall survival (OS) were significantly prolonged by combination therapy compared to BSC alone (PFS: 3 months vs 1.85 months, P < 0.05; OS: 9.4 months vs 5.6 months, P < 0.05). QoL was significantly increased in the active arm despite the advanced stage of disease. The 3-month disease control rate after treatment was 42.9% in the active arm and 16.7% in the control arm (P < 0.05). Overall, IVC and mEHT may have the ability to improve the prognosis of patients with advanced NSCLC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 THE AUTHORS. Published by Elsevier BV on behalf of Cairo University.)

Background and Purpose: Current practice in re-irradiation (reRT) of previously treated high-grade gliomas (HGG) has generally been limited to small volume reRT with stereotactic procedures. Less evidence exists for large volume reRT involving treatment volumes equivalent to that used at initial diagnosis. The primary aim of this study was to investigate the outcome of large volume reRT delivered in combination with Bevacizumab (BEV) in patients with recurrent chemorefractory HGG., Methods and Materials: Patients with HGG managed with reRT were entered prospectively into a database. Clinicopathological features were recorded including timing of reRT, use of BEV and Dosimetric data. Median survival following reRT was the primary endpoint and association with clinicopathological factors was assessed with cox regression models., Results: Sixty seven patients in total were managed with reRT, 51 patients had glioblastoma and 16 had anaplastic glioma. The median PTV was 145.3 cm 3 . Median OS post reRT was 7.8 months (95% CI 6.3-9.2 months) in the total cohort and 7.5 months (95% CI: 6.6-8.3 months) for GBM patients. In multivariate analysis of the whole cohort, IDH1 mutation status (p = 0.041) and ECOG status prior to reRT (<0.001) were significantly associated with OS. In terms of safety and toxicity, the majority of patients (66.5%) were ECOG 0-2 three months after treatment. In total, four episodes of suspected radiation necrosis occurred, all in patients treated without upfront BEV., Conclusion: Large volume reRT with bevacizumab is a feasible late salvage option in patients with recurrent HGG and offers meaningful prolongation of survival with low toxicity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Background: Lymphopenia during radiotherapy (RT) may have an adverse effect on treatment outcome. The aim of this study is to investigate associations between lymphopenia and RT parameters in patients with advanced lung cancer. Moreover, to investigate the prognostic role of lymphopenia, blood protein levels, and treatment and patient-related factors., Material and Methods: Sixty-two advanced stage non-small cell lung cancer (NSCLC) patients were retrospectively analyzed. Blood counts were available prior to, during, and after RT (3Gyx10). For each patient, a thoracic volume of interest (VOI) -including thoracic soft tissue and trabecular bone- was obtained by applying a CT window of -500 to 1200 HU in the planning CT. Dose parameters from thoracic VOI and other regions including lungs and vertebrae were calculated. Association between risk of lymphopenia ≥ G3 (lymphocytes at nadir according to CTCAE v4.0) and therapeutic parameters was investigated using Logistic regression. Relationships between overall survival (OS) and RT dose parameters, baseline blood counts and protein levels, and clinical factors were evaluated using Log-rank and Cox models., Result: Mean thoracic RT dose (odds ratio [OR] 1.67; p = 0.04), baseline lymphocytes (OR 0.65; p = 0.01), and corticosteroids use (OR 6.07; p = 0.02) were significantly associated with increased risk of lymphopenia ≥ G3 in multivariable analysis. Worse OS was associated with high mean thoracic RT dose, high CRP/Albumin, large tumor volume and corticosteroids use (p < 0.05, univariate analysis), but not with lymphopenia ≥ G3. CRP/Albumin ratio > 0.12 (hazard ratio [HR] 2.28, p = 0.03) and corticosteroid use (HR 2.52, p = 0.01) were independently associated with worse OS., Conclusion: High thoracic RT dose gave a higher risk of lymphopenia ≥ G3; hence limiting dose volume to the thorax may be valuable in preventing severe lymphopenia for patients receiving palliative fractionated RT. Still, lymphopenia ≥ G3 was not associated with worse OS. however, high baseline CRP/Albumin was associated with poorer OS and may carry important information as a prognostic factor of OS in advanced NSCLC receiving palliative RT., (© 2020 The Authors.)

Hepatocellular carcinoma (HCC) incidence and mortality have shown an unfavorable upward trend over the last two decades, especially in developed countries. More than one-sixth of the patients have advanced HCC at presentation. Systemic therapy remains the treatment of choice for these patients. Current options include tyrosine kinase inhibitors (TKIs) and immunotherapy. This review aims to summarize current knowledge on the rapidly evolving field of systemic therapy with several newly approved medications over the last year. Sorafenib remains one of the first-line treatment choices for patients with hepatitis C etiology, intermediate to advanced HCC stage, and Child-Pugh class A. Lenvatinib is the other first-line drug that might have better efficacy in non-hepatitis C etiologies and advanced HCC without portal vein thrombosis. Patients intolerant to first-line therapy might benefit from immunotherapy with nivolumab or pembrolizumab. In those who fail first-line therapy, the choice should be based on the side effects related to previous treatment, performance status, and underlying liver dysfunction. Ongoing studies are investigating immunotherapy alone or immunotherapy in combination with TKIs as first-line therapy. Several second-line options for combination systemic therapy and systemic plus local-regional treatment are under investigation. Future studies should focus on identifying reliable biomarkers to predict response to therapy and to better stratify patients at high risk for progression. Multidisciplinary approach is pivotal for successful outcomes in patients with advanced HCC., (© 2019 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objectives: To evaluate the incidence and risk factors for the development of flank incisional hernias or bulges following surgical flank approaches to the kidney., Patients and Methods: In all, 100 consecutive adult patients who underwent variable renal surgeries via flank approaches were included in this prospective study. The incidence and risk factors for flank hernias and bulges were studied at 1- and 6-months postoperatively., Results: At 6 months postoperatively, the incidence of flank bulge was 14% and for lumbar hernia was 10%. The univariate analysis showed 13 significant factors to be associated with the occurrence of a flank bulge or hernia following flank incisions. When the significant risk factors in the univariate analysis were studied by multivariate analysis, using a logistic regression analysis, four independent risk factors were identified. These were: body mass index (BMI) ≥26.3 kg/m 2 ( P  = 0.04), the use of a self-retaining retractor during surgery ( P  = 0.02), not preserving or identifying the neurovascular bundle (NVB) during surgery ( P  = 0.028), and postoperative abdominal distention ( P  = 0.001). Moreover, all cases included in our study who underwent en masse wound closure, developed surgical wound infection or who had constipation developed postoperative flank bulge or hernia., Conclusion: High BMI, the use of self-retaining retractor, not identifying or preserving the NVB, postoperative abdominal distention, en masse wound closure, surgical wound infection, and constipation are significant risk factors associated with postoperative flank hernia and bulge.

Background: This study identifies the overall survival status of lung cancer patients with bone metastasis and metastasis patterns. Poor prognostic factors were identified to develop a scoring system for estimating survival period after bone metastasis., Methods: A retrospective cohort analysis was performed at Chiang Mai University for the period January 1, 2006 and December 31, 2013. Time-to-event analysis was performed to estimate survival rate. The primary end point was death related to lung cancer. Univariate and multivariate analysis of the prognostic variables was done using the Cox's regression model. The score was derived from the corresponding estimated regression coefficients of significantly poor prognostic factors., Results: A total of 505 lung cancer with bone metastasis patients were analyzed. Four hundred two cases (79.6%) were concurrent diagnosis and 103 (20.4%) were subsequent diagnosis. The median survival time of lung cancer after bone metastasis 148 days. Male gender and ECOG 3-4 were significant poor prognostic factors for lung cancer after bone metastasis, with hazard ratios of 1.42 (95% CI 1.17-1.73), and 1.30 (95% CI 1.06-1.60), respectively. Prognosis score was determined using the binary term present/not-present for those factors. The curve from prognostic score summations of 2, 1 and 0 presented a good discrimination of survival expectancy, showing an expected median survival time of approximately 109, 146, and 225 days, respectively., Conclusions: Prognostic score is a clinically simple and easy method for estimating life expectancy and for guiding interventions in bone metastasis of lung cancer.

Introduction: The combination of a fluoropyrimidine [5-fluorouracil (5-FU), capecitabine, or S-1] with a platinum analog (cisplatin or oxaliplatin) is the most widely accepted first-line chemotherapy regimen for metastatic or recurrent advanced gastric cancer (AGC), based on the results of clinical trials. However, there is little evidence to guide chemotherapy for elderly patients with AGC because of under-representation of this age group in clinical trials. Thus, the aim of this study is to determine the optimal chemotherapy regimen for elderly patients with AGC by comparing the efficacies and safeties of combination therapy versus monotherapy as first-line chemotherapy., Methods: This study is a randomized, controlled, multicenter, phase III trial. A total of 246 elderly patients (≥70 years old) with metastatic or recurrent AGC who have not received previous palliative chemotherapy will be randomly allocated to a combination therapy group or a monotherapy group. Patients randomized to the combination therapy group will receive fluoropyrimidine plus platinum combination chemotherapy (capecitabine/cisplatin, S-1/cisplatin, capecitabine/oxaliplatin, or 5-FU/oxaliplatin), and those randomized to the monotherapy group will receive fluoropyrimidine monotherapy (capecitabine, S-1, or 5-FU). The primary outcome is the overall survival of patients in each treatment group. The secondary outcomes include progression-free survival, response rate, quality of life, and safety., Discussion: We are conducting this pragmatic trial to determine whether elderly patients with AGC will obtain the same benefit from chemotherapy as younger patients. We expect that this study will help guide decision-making for the optimal treatment of elderly patients with AGC.

Background: Skeletal-related events (SREs; pathologic fracture, radiation or surgery to bone, spinal cord compression) frequently occur in patients with advanced cancer with bone metastases/lesions. Limited data on the associated patient and economic burden are available to aid in resource planning and evaluating treatment options., Methods: Patients with bone metastases/lesions secondary to breast, lung or prostate cancer or multiple myeloma; with at least one SRE within 97 days prior to enrollment; life expectancy of at least 6 months; and Eastern Cooperative Oncology Group performance status 0, 1 or 2 were recruited. Information on health resource utilization (HRU; including number/duration of hospitalizations, outpatient visits, procedures), attributed by investigators to be associated with a SRE, was collected retrospectively for up to 97 days prior to enrollment and prospectively for up to 18-21 months., Results: A total of 631 patients contributing 1282 SREs, were enrolled across Germany, Italy, Spain and the United Kingdom. Approximately a third of all SREs required an inpatient stay. Mean duration of inpatient stay for patients with SREs requiring one ranged from 8.4 to 41.1 days across all countries and SRE types., Conclusion: All types of SREs are associated with substantial HRU burden. Preventing SREs by using the best therapeutic options available may help to reduce the burden to patients and healthcare systems.

The identification of tumor-associated antigens (TAA) has made possible the development of antigen-specific cancer immunotherapies such as tecemotide. One of those is mucin 1 (MUC1), a cell membrane glycoprotein expressed on some epithelial tissues such as breast and lung. In cancer, MUC1 becomes overexpressed and aberrantly glycosylated, exposing the immunogenic tandem repeat units in the extracellular domain of MUC1. Designed to target tumor associated MUC1, tecemotide is being evaluated in Phase III clinical trials for treatment of unresectable stage IIIA/IIIB non-small cell lung cancer (NSCLC) as maintenance therapy following chemoradiotherapy. Additional Phase II studies in other indications are ongoing. This review discusses the preclinical and clinical development of tecemotide, ongoing preclinical studies of tecemotide in human MUC1 transgenic mouse models of breast and lung cancer, and the potential application of these models for optimizing the timing of chemoradiotherapy and tecemotide immunotherapy to achieve the best treatment outcome for patients.

Purpose: The ZOTECT study assesses the effect of zoledronic acid (ZOL) on bone-marker levels and potential correlations with disease outcomes in bisphosphonate-naive patients., Methods: This prospective, single-arm, open-label study in bisphosphonate-naive (≥6 months) patients with bone metastases from prostate cancer (PC; n=301) or breast cancer (BC; n=99) enrolled at 98 German sites (May 2006 to July 2008) investigated the effect of ZOL (4 mg intravenously every 4 weeks×4 months, with a final follow-up at 12 months) on bone-marker levels. Secondary assessments: skeletal-related event (SRE) rate, pain, quality of life (QoL), and prostate-specific antigen levels. Endpoints were assessed using summary statistics by visit/tumor type and Kaplan-Meier analyses., Results: ZOL treatment significantly decreased bone-marker levels (amino-terminal propeptide of type I collagen [P1NP], C-terminal cross-linking telopeptide of type I collagen [CTX]; P<0.0001), and this decrease was maintained through the final 1-year follow-up visit. Baseline P1NP and CTX levels correlated with extent of bone disease (P<0.0001, each) and on-treatment decreases in marker levels. Skeletal disease burden and bone-marker levels were similar between PC and BC patients, and ZOL did not significantly influence osteoprotegerin/receptor activator of nuclear factor-κB ligand levels. Only 13 SREs occurred in 11 patients, supporting the known ZOL-mediated reduction in SREs. On-treatment bone-marker level changes did not correlate with SRE rate, pain scores, or QoL. Generally, ZOL was well tolerated and adverse events were consistent with its known safety profile., Conclusions: This study confirms that ZOL therapy significantly reduces bone turnover (measured as P1NP and CTX levels) in patients with bone metastases from PC or BC.