Oncology

Interaction of H. pylori with toll-like receptor 2-196 to -174 ins/del polymorphism is associated with gastric cancer susceptibility in southern China Abstract Background Genetic polymorphisms of Toll-like receptors play important roles in gastric carcinogenesis. The aim of this study was to determine the role of TLR2-196 to -174 ins/del polymorphism in gastric cancer susceptibility and prognosis. Methods This study included 520 people from southern China. Samples were genotyped by the allele-specific polymerase chain reaction, among which 10% were randomly selected for sequencing. The serological method was used to determine Helicobacter pylori. Results The TLR2 genotype was not associated with the risk of H. pylori infection. The del/del genotype exhibited significantly higher gastric cancer risk (adjusted OR 2.59, 95% CI 1.33‒5.07) than that of the ins/ins genotype. Further stratification analyses demonstrated that the del/del genotype was associated with a risk of intestinal gastric cancer (adjusted OR 2.62, 95% CI 1.34–5.14). In addition, the presence of the del/del genotype and the H. pylori infection conferred a synergistic effect (OR 3.04, 95% CI 1.33‒6.98) for the development of gastric cancer. The del/del genotype was not associated with a poor prognosis in gastric cancer patients. Conclusion The del/del genotype is associated with an increased gastric cancer risk in the southern Chinese population. However, TLR2 polymorphism is neither associated with H. pylori infection, nor with a poor prognosis.

A multi-institutional observational study on the effects of three-dimensional radiotherapy and weekly 40-mg/m 2 cisplatin on postoperative uterine cervical cancer patients with high-risk prognostic factors Abstract Background The aim of this study was to evaluate the effects of treatment with both three-dimensional radiotherapy (3DRT) and weekly 40-mg/m2 cisplatin on postoperative uterine cervical cancer patients with high-risk prognostic factors. Methods We conducted a retrospective multi-institutional chart review of postoperative uterine cervical cancer patients with high-risk prognostic factors who had been treated with both 3DRT and weekly 40-mg/m2 cisplatin from 2007 to 2012. Each participating hospital provided detailed information regarding patient characteristics, treatment outcomes, and treatment complications. Results The eligible 96 patients were analyzed. The median follow-up period was 61 months. The 3-year relapse-free survival, overall survival (OS), and locoregional relapse-free survival (LRFS) rates were 76%, 90%, and 88%, respectively. In multivariate analysis, the histological finding of either adenocarcinoma or adenosquamous carcinoma was a significant risk factor for both OS and LRFS. The percentage of patients with grade ≥ 3 acute hematologic toxicity, acute lower gastrointestinal toxicity (GIT), and late lower GIT were 45%, 19%, and 17%, respectively. Conclusions The outcomes of concurrent chemoradiotherapy (CCRT) using weekly 40-mg/m2 cisplatin are similar to those in the previous studies that used several chemotherapy regimens. However, postoperative CCRT using 3DRT had a high level of late GIT.

Clinical factors associated with the therapeutic outcome of chemotherapy in very elderly cancer patients Abstract Background The purpose of this study was to detect background factors that might be associated with the therapeutic and curative outcome of chemotherapy in elderly cancer patients aged over 75 years. Methods A retrospective study was conducted for elderly cancer patients aged over 75 years who had received more than 2 courses of chemotherapy at our hospital. We analyzed the relationships between RECIST outcome and background factors, such as age, sex, clinical TNM stage, pre-treatment history, ECOG performance status, serum albumin, and Charlson comorbidity index using logistic regression analysis. Results A total of 103 cancer patients aged over 75 years were analyzed in this study, including 28 with hematological neoplasia, 36 with gastrointestinal tract cancers, 25 with breast cancers, and 14 with other malignancies originating in various tissues. Seventy-one patients (69.1%) had a positive clinical outcome including RECIST CR (complete response), PR (partial response) and SD (stable disease). Multivariate analysis showed that a high serum albumin level of more than 3.5 g/dl and a Charlson comorbidity index score of less than 2 points were positively correlated with a favorable therapeutic outcome. Conclusions The results of the current study suggested that serum albumin level and comorbidity index are the principal clinical factors affecting therapeutic outcomes in elderly cancer patients receiving chemotherapy. In the future, these factors may make chemotherapy adaptations, continuity, and effectiveness easier to predict than GA screening.

Safety and efficacy of concurrent carboplatin or cetuximab plus radiotherapy for locally advanced head and neck cancer patients ineligible for treatment with cisplatin Abstract Background Locally advanced squamous cell carcinoma of the head and neck (LASCCHN) is usually treated with cisplatin (CDDP)-based chemoradiotherapy, except when patients are elderly or have renal, cardiac, or neurogenic dysfunction. This study compared the safety and efficacy of concurrent carboplatin (CBDCA) to cetuximab (Cmab) plus radiotherapy (RT) in patients ineligible for CDDP treatment. Methods We retrospectively analyzed LASCCHN patients who received CBDCA plus RT (n = 29) or Cmab plus RT (n = 18) due to ineligibility for CDDP treatment at two Japanese institutions between August 2006 and December 2015. Results Patients characteristics for CBDCA plus RT and Cmab plus RT were: median age, 74 and 75 years; 0–1 performance status, 90% and 100%; main primary tumor site, hypopharynx 52% (n = 15) and oropharynx 39% (n = 7); and stage IV, 90% (n = 26) and 50% (n = 9), respectively. With a median follow-up time of 60.0 months for CBDCA plus RT and 53.6 months for Cmab plus RT, 3-year locoregional control rates were 56% versus 58%, and median progression-free survival was 42.7 versus 11.6 months. CBDCA plus RT was associated with more grade 3/4 hematologic toxicities, including neutropenia and thrombocytopenia, whereas Cmab plus RT was associated with more grade 3/4 oral mucositis and radiation dermatitis. Conclusions CBDCA or Cmab as a concurrent systemic therapy with RT is a possible treatment option for LASCCHN patients ineligible for CDDP treatment, although attention to hematological toxicity should be paid.

Optimal maximum duration for delaying salvage operation when recurrence of retroperitoneal liposarcoma is suspected: a single-center study Abstract Background This study was designed to identify the optimal maximum duration for delaying salvage operation when recurrence of retroperitoneal liposarcoma (LPS) is suspected. Methods Patients who underwent salvage operation at Samsung Medical Center for recurrent retroperitoneal LPS from January 2000 to December 2015 were reviewed. The time interval between recurrence and operation for recurrence was divided by 1, 2 or 3 months. A Cox proportional-hazards model was used to analyze factors related to disease-free survival along with recurrence-to-operation interval divided by 1, 2 or 3 months. Results The 1-, 3-, and 5-year disease-free survival rates were 43.2%, 15.6% and 13.4%, respectively. FNCLCC grade (p = 0.023) and recurrence-to-operation interval divided by 3 months (p = 0.003) were significant factors associated with recurrence. FNCLCC grade 2 (HR 1.940, CI 0.935–4.026, p = 0.238) and grade 3 (HR 4.049, CI 1.767–9.281, p = 0.007) showed increased risk compared to grade 1. Patients who underwent salvage operation more than 3 months after recurrence showed significantly increased risk of recurrence compared to patients within 3 months (HR 2.724, CI 1.391–5.337, p = 0.003). Conclusions Based on our analysis of recurrence-free survival, salvage operation can be delayed for less than 3 months when recurrence is suspected. A short-term follow-up imaging study should be performed within this period.

Castration-resistant prostate cancer patients who had poor response on first androgen deprivation therapy would obtain certain clinical benefit from early docetaxel administration Abstract Background Our specific aim was to investigate the prognostic value of effective duration of first androgen deprivation therapy (ADT) and to evaluate the clinical impact on early docetaxel administration with oncological outcomes in castration-resistant prostate cancer (CRPC) patients treated with docetaxel. Methods We identified 148 mCRPC patients who were treated with 75 mg/m2 docetaxel. We defined 16 months as the threshold for the effective duration of ADT, and defined 12 months as the cut-off time for starting docetaxel from the onset of CRPC. Univariate and multivariate analyses were conducted to investigate the prognostic indicators that influenced the survival outcomes. Results Overall, 81 (54.7%) patients died. The median 1st ADT response was 22.2 months and the median time interval from CRPC onset to docetaxel treatment was 11.7 months. Multivariate analysis indicated that visceral metastasis, bone metastasis extent of disease (EOD) ≥ 2, and effective duration of ADT < 16 months were the independent prognostic indicators for progression-free survival (PFS). Referring to cancer-specific survival (CSS), besides visceral metastasis and effective duration of ADT < 16 months, late docetaxel treatment ≥ 12 months became as the predictors for poor prognosis. Among the ADT poor-responder group (ADT < 16 months), Kaplan–Meier method showed that 1-year and 2-year CSS rates were 96.0% and 80.0% in the patients who introduced docetaxel in early setting (< 12 months), which were significantly higher than those who introduced in late settings (93.6% and 30.8%, respectively, p < 0.001). Conclusion CRPC patients who had poor response during 1st ADT would obtain survival benefit by introducing docetaxel treatment in early stage.

External validation of the systemic immune-inflammation index as a prognostic factor in metastatic renal cell carcinoma and its implementation within the international metastatic renal cell carcinoma database consortium model Abstract Background We conducted a study to validate the influence of the systemic immune-inflammation index (SII) on overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) and to verify whether the implementation of the SII in place of neutrophil and platelet counts within the International Metastatic Renal Cell Carcinoma Consortium (IMDC) model might increase its prognostic accuracy. Patients and methods We retrospectively analyzed consecutive patients with mRCC, who were treated with first-line tyrosine kinase inhibitors from 2008 to 2016 in two major oncology centres in Poland. We stratified patients into low SII (< 730) and high SII (≥ 730) groups according to a recent literature report. We used multivariable Cox proportional hazards regressions (CPHRs) to assess the impact of the SII on OS and concordance, global 'goodness-of-fit', calibration and reclassification measures to quantify a potential prognostic benefit from the modification of the IMDC model. Results Overall, 502 patients (294 with low and 208 with high SII) were included. Median OS was 36.7 months [95% confidence interval (CI) 30.4–41.5 months] and 17.0 months (95% CI 12.5–19.6 months) in the low and high SII groups, respectively. The SII status was significant in CPHRs with the hazard ratio ranging from 1.38 to 1.68. All prognostic accuracy measures favored the SII-modified-IMDC model over the original IMDC model. Conclusions Using an external dataset, we showed that high SII was an independent factor for poor OS. The addition of the SII to the IMDC model in place of neutrophil and platelet counts increased the model's prognostic performance.

Recent treatment strategy for advanced squamous cell carcinoma of the lung in Japan Abstract Squamous cell carcinoma of the lung is associated with smoking in its development and comprises about 20–30% of all lung cancers. Its treatment strategy had been limited for the past decades, inevitably resulting in the poor outcome. However in the 2010s, it has dramatically changed mainly with the recent clinical introduction of immune checkpoint inhibitors. In this review, we will introduce various clinical studies involving squamous cell carcinoma of the lung.

Preoperative predictive factors focused on inflammation-, nutrition-, and muscle-status in patients with upper urinary tract urothelial carcinoma undergoing nephroureterectomy Abstract Objective The present study evaluated the clinical relevance of an integrative preoperative assessment of inflammation-, nutrition-, and muscle-based markers for patients with upper urinary tract urothelial carcinoma (UTUC) undergoing curative nephroureterectomy (NUx). Methods The study enrolled 125 patients and the preoperative variables assessed included age, body mass index, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), serum fibrinogen level (Fib), C-reactive protein (CRP), modified Glasgow prognostic score, serum albumin level (Alb), prognostic nutritional index (PNI), skeletal muscle index (SMI), psoas muscle index (PMI), and peak expiratory flow (PEF). The correlations among the variables and their prognostic values after NUx were evaluated. Results Five inflammation markers (NLR, MLR, PLR, Fib and CRP) were positively correlated. Fib was positively correlated with NLR, PLR and CRP, but inversely correlated with SMI. PNI was inversely correlated with age and the four inflammation markers (p < 0.001). Age was not significantly correlated with the inflammation markers, but older age was associated with lower Alb, PNI, SMI, PMI, and PEF. Disease-specific survival was independently predicted by preoperative ipsilateral hydronephrosis and low PNI. Overall survival was independently associated with high Fib and low PNI. Conclusion The preoperative inflammation-, nutrition-, and muscle-based markers would be useful risk assessment tools for UTUC.