In addition to wirelength, modern placers need to consider various constraints such as preplaced blocks and density. We propose a high-quality analytical placement algorithm considering wirelength, ...preplaced blocks, and density based on the log-sum-exp wirelength model proposed by Naylor and the multilevel framework. To handle preplaced blocks, we use a two-stage smoothing technique, i.e., Gaussian smoothing followed by level smoothing, to facilitate block spreading during global placement (GP). The density is controlled by white-space reallocation using partitioning and cut-line shifting during GP and cell sliding during detailed placement. We further use the conjugate gradient method with dynamic step-size control to speed up the GP and macro shifting to find better macro positions. Experimental results show that our placer obtains very high-quality results.
Head and neck cancer (HNC) is one of the 10 most frequent cancers worldwide, with an estimated over 500 000 new cases being diagnosed annually. The overall 5‐year survival rate in patients with HNC ...is one of the lowest among common malignant neoplasms and has not significantly changed during the last two decades. Oral cavity squamous cell carcinoma (OSCC) shares part of HNC and has been reported to be increasing in the betel quid chewing area in recent years. During 2006, OSCC has become the sixth most common type of cancer in Taiwan, and it is also the fourth most common type of cancer among men. It follows that this type of cancer wreaks a high social and personal cost. Environmental carcinogens such as betel quid chewing, tobacco smoking and alcohol drinking have been identified as major risk factors for head and neck cancer. There is growing interest in understanding the relationship between genetic susceptibility and the prevalent environmental carcinogens for HNC prevention. Within this review, we discuss the molecular and cellular aspects of HNC carcinogenesis in Taiwan, an endemic betel quid chewing area. Knowledge of molecular carcinogenesis of HNC may provide critical clues for diagnosis, prognosis, individualization of therapy and molecular therapeutics. (Cancer Sci 2008; 99: 1507–1514)
Background
This study aimed to evaluate the role of baseline circulating tumor cells (CTCs) before and during concurrent chemoradiotherapy and attempted to determine the impacts of CTCs on the ...outcomes in patients with head and neck squamous cell carcinoma.
Methods
CTCs were detected using a negative selection strategy and flow cytometry protocol.
Results
We observed a significant correlation between baseline CTCs and staging (P = 0.001). The CTC counts were significantly reduced within 2‐4 weeks in 47 concurrent chemoradiotherapy responders (P < 0.001). Change of CTC counts correlates with progression‐free survival (PFS, P = 0.01) and overall survival (OS, P = 0.01). CTC decline status was an independent prognostic factor in PFS (P = 0.03) and OS (P = 0.05) in multivariate analyses.
Conclusion
In chemoradiotherapy responders, CTCs are significantly reduced. CTC decline within the first month indicates a longer PFS and OS, suggesting that the dynamics of CTCs could be more important than CTC number alone.
Background
Fatigue is a common symptom in cancer patients receiving radiotherapy. However, previous studies report inconsistent patterns of fatigue change.
Aim
The aim of this study was to estimate ...changes in fatigue among patients with cancer before, during, and after radiotherapy.
Methods
Five databases (PubMed, SDOL, CINAHL Plus with Full Text, Medline ProQuest, and ProQuest Dissertations) were searched for studies published from January 2006 to May 2021. Three effect sizes of fatigue change (immediate, short‐term, and long‐term) were calculated for each primary study using standardized mean difference. A random‐effect model was used to combine effect sizes across studies. Subgroup analyses and meta‐regression were performed to identify potential categorical and continuous moderators, respectively.
Results
Sixty‐five studies were included in this meta‐analysis. The weighted mean effect size for immediate, short‐term, and long‐term effects was 0.409 (p < .001; 95% CI 0.280, 0.537), 0.303 (p < .001; 95% CI 0.189, 0.417), and 0.201 (p = .05; 95% CI −0.001, 0.404), respectively. Studies with prostate cancer patients had a significantly higher short‐term (0.588) and long‐term weight mean effect size (0.531) than studies with breast (0.128, −0.072) or other cancers (0.287, 0.215). Higher radiotherapy dosage was significantly associated with a higher effect size for both immediate (β = .0002, p < .05) and short‐term (β = .0002, p < .05) effect.
Linking Evidence to Action
Findings from this meta‐analysis indicated that radiotherapy‐induced fatigue (RIF) exist for more than 3 months after the completion of treatment. Assessment of radiation‐induced fatigue in cancer patients should extend long after treatment completion, especially for patients with prostate cancer and patients receiving a higher radiation dose. Interventions to reduce fatigue tailored for different treatment phases may be developed.
Objective To study the prevalence of and risk factors associated with carotid artery stenosis (CAS) after radiotherapy (RT) for head and neck cancer. Methods Design of study: Prospective, ...cross-sectional study. Setting: Patients recruited from a hospital Radiation-Oncology department. Subjects: From March 2002 to August 2006, 290 consecutive head and neck cancer patients were enrolled in this study. One hundred ninety-two of these patients had previously undergone RT (RT group) and 98 had no RT (control group). Intervention: After detecting CAS by carotid duplex sonography, the severity of CAS was evaluated by a bilateral plaque scoring system. Main outcome measure: CAS score. Results There were no differences in age or gender between the two groups. The RT group had a significantly higher plaque score than the non-irradiated group ( P < .05). Multiple regression analysis of the 290 head and neck cancer patients revealed that bilateral plaque score was significantly correlated with age, hyperlipidemia, and RT. Multiple regression analysis was performed in the RT group alone with patients 41-50 years old serving as the reference group. This analysis showed that in RT patients > 50 years old, age was inversely correlated with plaque score; however, in RT patients ≤ 41 years old, age was positively correlated with plaque score. Conclusion In head and neck cancer, the high post-treatment incidence of radiation-induced CAS indicates the importance of regular examination of the carotid duplex and early antiplatelet prophylaxis. Different age groups may require different irradiation strategies to prevent radiation-induced CAS.
Objectives/Hypothesis
Elevated inflammatory biomarkers such as C‐reactive protein (CRP) and the recently identified neutrophil/lymphocyte ratio (NLR) were demonstrated to be associated with prognosis ...in human cancers. The aim of our present study is to analyze the relationship of preoperative levels of CRP and NLR with clinicopathological factors and prognosis in oral squamous cell carcinoma (OSCC) patients.
Study Design
Retrospective study.
Methods
This study was performed on 226 OSCC patients between July 2007 and April 2012. Their serum CRP levels and NLR were measured preoperatively.
Results
CRP level ≥ 5.0 mg/L was significantly associated with NLR ≥ 2.44 (linear regression, P < .001). Elevated CRP and NLR were significantly associated with pathological tumor status (P < .001), pathologic nodal metastasis (P < .001), tumor depth (≥10 mm vs. <10 mm, P < .001), disease‐free survival (P < .001), and overall survival (P = .001). The influence of CRP level and NLR on disease‐free survival (hazard ratio HR = 2.259, 95% confidence interval CI = 1.170‐4.361) and overall survival (HR = 2.176, 95% CI = 1.116‐4.245) still existed after adjusting for tumor status, lymph node metastasis, and tumor cell differentiation.
Conclusions
The present study demonstrates that elevated CRP is an independent prognostic factor in OSCC. Elevated NLR in the high CRP group identifies patients at high risks of recurrence and shorter survival. Incorporating NLR into CRP level therefore has significant potential as a biomarker for risk stratification in OSCC.
Level of Evidence
4. Laryngoscope, 123:2690–2699, 2013
This study compared the effects of megestrol acetate (MA) prophylactic (p-MA) versus reactive (r-MA) use for critical body-weight loss (>5% from baseline) during concurrent chemoradiotherapy (CCRT) ...in patients with advanced pharyngolaryngeal squamous cell carcinoma (PLSCC).
Patients receiving CCRT alone in two phase-II trials were included for analyses. Both the p-MA and r-MA cohorts received the same treatment protocol at the same institution, and the critical body-weight loss, survival, and adverse event profiles were compared.
The mean (SD) weight loss was 5.1% (4.7%) in the p-MA cohort (n = 54) vs. 8.1% (4.6%) in the r-MA cohort (n = 50) (p = .001). The percentage of subjects with body-weight loss >5% was 42.6% in the p-MA cohort vs. 68.0% in the r-MA cohort (p = .011). Tube feeding was needed in 22.2% of p-MA vs. 62.0% of r-MA patients (p < .001). Less neutropenia (26.0% vs. 70.0% p < .001) and a shorter duration of grade 3-4 mucositis (2.4 ± 1.4 vs. 3.6 ± 2.0 wk p = .009) were observed with p-MA treatment. Disease-specific survival, locoregional control, or distant metastasis-free survival did not differ. Less competing mortality from secondary primary cancer resulted in a better overall survival trend in the p-MA cohort.
p-MA may reduce body-weight loss and improve adverse event profiles during CCRT for patients with PLSCC.
To identify predictors of radiation-induced liver disease (RILD) in patients with hepatocellular carcinoma (HCC) treated with proton beam therapy (PBT).
This multicenter study included 136 patients ...with HCC (eastern, n = 102; western, n = 34) without evidence of intrahepatic tumor progression after PBT. The RILD was defined as ascites with alkaline-phosphatase abnormality, grade ≥3 hepatic toxicity, or Child-Pugh score worsening by ≥2 within 4 months after PBT completion. The proton doses were converted to equivalent doses in 2-GyE fractions. The unirradiated liver volume (ULV) was defined as the absolute liver volume (LV) receiving <1 GyE; the standard liver volume (SLV) was calculated using body surface area. Possible correlations of clinicodosimetric parameters with RILD were examined.
The mean pretreatment LV was 85% of SLV, and patients with a history of hepatectomy (P < .001) or hepatitis B virus infection (P = .035) had significantly smaller LV/SLV. Nineteen (14%) patients developed RILD. Multivariate logistic regression analysis identified ULV/SLV (P = .001), gross tumor volume (P = .001), and Child-Pugh classification (P = .002) as independent RILD predictors, and mean liver dose and target-delivered dose were not associated with RILD occurrence. A "volume-response" relationship between ULV/SLV and RILD was consistently observed in both eastern and western cohorts. In Child-Pugh class-A patients whose ULV/SLV were ≥50%, 49.9%-40%, 39.9%-30% and <30%, the RILD incidences were 0%, 6%, 16%, and 39% (P < .001), respectively. For the Child-Pugh class-B group, the RILD incidences in patients with ≥60%, 59.9%-40%, and <40% of ULV/SLV were 0%, 14%, and 83% (P = .006), respectively.
The ULV/SLV, not mean liver dose, independently predicts RILD in patients with HCC undergoing PBT. The relative and absolute contraindications for Child-Pugh class-A patient's ULV/SLV are <50% and <30%, and <60% and <40% for Child-Pugh class-B patients, respectively. Our results indicate that the likelihood of hepatic complications for PBT is dictated by similar metrics as that for surgery.
Head and neck cancer (HNC) is the fifth most common cancer worldwide, and its incidence and death rates have been consistently high throughout the past decades. MicroRNAs (miRNAs) have recently ...gained significant attention because of their role in the regulation of a variety of biological processes via post-transcriptional silencing mechanisms. Previously, we determined a specific profile of miRNAs associated with HNC using a miRNA microarray analysis. Of the 23 miRNAs with highly altered expression in HNC cells, miR-503 was the most significantly downregulated miRNA. In this study, we confirmed that miR-503 acts as a tumor suppressor, as our results showed decreased levels of miR-503 in cancer cells and patients with HNC. We further characterized the role of miR-503 in the malignant functions of HNC. Although there was a minimal effect on cell growth, miR-503 was found to inhibit cellular invasion significantly. Algorithm-based studies identified multiple potential target genes and pathways associated with oncogenic mechanisms. The candidate target gene, WNT3A, was confirmed to be downregulated by miR-503 at both the mRNA and protein levels and validated by a reporter assay. Furthermore, miR-503 modulated multiple invasion-associated genes, including matrix metalloproteinases (MMPs), through the Wnt downstream signaling pathway. Overall, this study demonstrates that miR-503 suppresses HNC malignancy by inhibiting cell invasion through the Wnt signaling pathway via the WNT3A/MMP molecular axis. The modulation of miR-503 may be a novel therapeutic approach to intervene in cancer invasion.
The aim of this study was to determine whether the oncogenic microRNA family members miR-196a and miR-196b can be circulating biomarkers for the early detection of oral cancer.
To determine the ...stability of circulating miRNA, the blood sample was aliquot and stored at different temperature conditions for analysis. To assess the diagnostic efficacy, we determined the levels of miR-196s in plasma samples, including 53 from healthy individuals, 16 from pre-cancer patients, and 90 from oral cancer patients.
In general, circulating miRNA was very stable when storing plasma samples at -20°C or below. In clinical study, both circulating miR-196a and miR-196b were substantially up-regulated in patients with oral pre-cancer lesions (5.9- and 14.8-fold, respectively; P<0.01), as well as in oral cancer patients (9.3- and 17.0-fold, respectively; P<0.01). These results show prominent discrimination between normal and pre-cancer patients (AUC=0.764 or 0.840, miR-196a or miR-196b, respectively), and between normal and cancer patients (AUC=0.864 or 0.960, miR-196a or miR-196b, respectively). The combined determination of miR-196a and miR-196b levels produces excellent sensitivity and specificity in the diagnosis of patients with oral pre-cancer (AUC=0.845) or oral cancer (AUC=0.963), as well as in the prediction of potential malignancy (AUC=0.950, sensitivity=91%, specificity=85%).
Combined determination of circulating miR-196a and miR-196b levels may serve as panel plasma biomarkers for the early detection of oral cancer.
•miR-196a/b are elevated in the plasma of oral cancer and pre-cancer patients.•The elevations of miR-196a/b in oral cancer patients are associated with T stage.•miR-196a provides excellent specificity for the diagnosis of oral malignancy.•miR-196b provides super sensitivity for the screening of oral malignancy.•Panel miR-196s serve as excellent biomarkers for early detection of oral cancer.
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