Shih Kai Hung

Clinical application of tumor volume in advanced nasopharyngeal carcinoma to predict outcome

BackgroundCurrent staging systems have limited ability to adjust optimal therapy in advanced nasopharyngeal carcinoma (NPC). This study aimed to delineate the correlation between tumor volume, treatment outcome and chemotherapy cycles in advanced NPC.MethodsA retrospective review of 110 patients with stage III-IV NPC was performed. All patients were treated first with neoadjuvant chemotherapy, then concurrent chemoradiation, and followed by adjuvant chemotherapy as being the definitive therapy. Gross tumor volume of primary tumor plus retropharyngeal nodes (GTVprn) was calculated to be an index of treatment outcome.ResultsGTVprn had a close relationship with survival and recurrence in advanced NPC. Large GTVprn (≧13 ml) was associated with a significantly poorer local control, lower distant metastasis-free rate, and poorer survival. In patients with GTVprn ≧ 13 ml, overall survival was better after ≧4 cycles of chemotherapy than after less than 4 cycles.ConclusionsThe incorporation of GTVprn can provide more information to adjust treatment strategy.

Buccal mucosa carcinoma: surgical margin less than 3 mm, not 5 mm, predicts locoregional recurrence

BackgroundMost treatment failure of buccal mucosal cancer post surgery is locoregional recurrence. We tried to figure out how close the surgical margin being unsafe and needed further adjuvant treatment.MethodsBetween August 2000 and June 2008, a total of 110 patients with buccal mucosa carcinoma (25 with stage I, 31 with stage II, 11 with stage III, and 43 with Stage IV classified according to the American Joint Committee on Cancer 6th edition) were treated with surgery alone (n = 32), surgery plus postoperative radiotherapy (n = 38) or surgery plus adjuvant concurrent chemoradiotherapy (n = 40).Main outcome measures: The primary endpoint was locoregional disease control.ResultsThe median follow-up time at analysis was 25 months (range, 4-104 months). The 3-year locoregional control rates were significantly different when a 3-mm surgical margin (≤3 versus >3 mm, 71% versus 95%, p = 0.04) but not a 5-mm margin (75% versus 92%, p = 0.22) was used as the cut-off level. We also found a quantitative correlation between surgical margin and locoregional failure (hazard ratio, 2.16; 95% confidence interval, 1.14 - 4.11; p = 0.019). Multivariate analysis identified pN classification and surgical margin as independent factors affecting disease-free survival and locoregional control.ConclusionsNarrow surgical margin ≤3 mm, but not 5 mm, is associated with high risk for locoregional recurrence of buccal mucosa carcinoma. More aggressive treatment after surgery is suggested.

Survival rate in nasopharyngeal carcinoma improved by high caseload volume: a nationwide population-based study in Taiwan

BackgroundPositive correlation between caseload and outcome has previously been validated for several procedures and cancer treatments. However, there is no information linking caseload and outcome of nasopharyngeal carcinoma (NPC) treatment. We used nationwide population-based data to examine the association between physician case volume and survival rates of patients with NPC.MethodsBetween 1998 and 2000, a total of 1225 patients were identified from the Taiwan National Health Insurance Research Database. Survival analysis, the Cox proportional hazards model, and propensity score were used to assess the relationship between 10-year survival rates and physician caseloads.ResultsAs the caseload of individual physicians increased, unadjusted 10-year survival rates increased (p < 0.001). Using a Cox proportional hazard model, patients with NPC treated by high-volume physicians (caseload ≥ 35) had better survival rates (p = 0.001) after adjusting for comorbidities, hospital, and treatment modality. When analyzed by propensity score, the adjusted 10-year survival rate differed significantly between patients treated by high-volume physicians and patients treated by low/medium-volume physicians (75% vs. 61%; p < 0.001).ConclusionsOur data confirm a positive volume-outcome relationship for NPC. After adjusting for differences in the case mix, our analysis found treatment of NPC by high-volume physicians improved 10-year survival rate.

13-year nationwide cohort study of chronic kidney disease risk among treatment-naïve patients with chronic hepatitis B in Taiwan

BackgroundChronic hepatitis B virus (HBV) infection and chronic kidney disease (CKD) have high prevalences in Taiwan and worldwide. However, the association of untreated chronic hepatitis B virus (HBV) infection with chronic kidney disease (CKD) remains unclear.MethodsThis cohort study used claims data in the Taiwan National Health Insurance Research Database in 1996–2010, in which all diseases were classified by ICD-9-CM codes. We identified 17796 adults who had chronic HBV infection and did not take nucleos(t)ide analogues from 1998 to 2010 and also randomly selected 71184 matched controls without HBV in the same dataset. Cumulative incidences and adjusted hazard ratio (aHR) of incident CKD were evaluated through the end of 2010 after adjusting for competing mortality.ResultsThe risk of CKD was significantly higher in the HBV cohort (13-year cumulative incidence, 6.2xa0%; 95xa0% confidence interval [CI], 5.4–7.1xa0%) than in the non-HBV cohort (2.7xa0%; 95xa0% CI, 2.5–3.0xa0%) (pu2009<u20090.001), and the aHR was 2.58 (95xa0% CI, 1.95-3.42; pu2009<u20090.001). Multivariable stratified analysis further verified significant associations of CKD with HBV in men of any age (aHR, 2.98; 95xa0% CI, 2.32–3.83, pu2009<u20090.001 for men aged <50xa0years; aHR, 1.58; 95xa0% CI, 1.31–1.91, pu2009<u20090.001 for men aged ≧50xa0years) and women under the age of 50 (aHR, 2.99; 95xa0% CI, 2.04–4.42, pu2009<u20090.001), but no significant association in women aged 50 or over.ConclusionUntreated chronic HBV infection is associated with increased risk of CKD. Hence, high-risk HBV-infected subjects should have targeted monitoring for the development of CKD.

Effect of 23-valent pneumococcal polysaccharide vaccine inoculated during anti-cancer treatment period in elderly lung cancer patients on community-acquired pneumonia hospitalization: A nationwide population-based cohort study

AbstractTo evaluate effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPSV23) inoculated during defined “vaccination period,” first 6 months post cancer diagnosis (ie, an anti-cancer treatment period), in elderly lung cancer patients on community-acquired pneumonia (CAP) hospitalization incidence.This was a nationwide population-based cohort study of 157 newly diagnosed elderly lung cancer patients receiving PPSV23 during “vaccination period”, and 628 age and sex one-to-one matched controls enrolled in the National Health Insurance Research Database (NHIRD) of Taiwan between 2007 and 2010. All patients were ≥75 years old and still survival post “vaccination period.” Incidence density (ID) of all-cause inpatient CAP and cumulative survival risk were analyzed by multivariate Poisson regression and Kaplan–Meier method, respectively.After a 4-year follow-up, IDs of all-cause inpatient CAP for vaccination and control cohorts were 297 and 444 per 1000 PYs, respectively. Less vaccinated patients had CAP incidence density >1 time per PY (12.7% vs 21.2%) than non-vaccinated patients. After adjusting for potential confounding variables, like influenza vaccination, comorbidities, cancer treatment modalities, and socioeconomic status, adjusted inpatient CAP incidence rate in PPSV23 vaccination cohort was 0.74 times lower than control cohort (incidence rate ratio [IRR]u200a=u200a0.740, Pu200a=u200a0.0339). Two-year cumulative CAP hospitalization rates and overall survival rates were 37.1% vs. 55.4%, and 46.6% vs. 26.2%, respectively, for lung cancer patients with and without PPSV23 (both Pu200a<u200a0.001). Subgroup analysis showed that for elderly lung cancer patients not ever receiving influenza vaccine, PPSV23 still had trend to reduce all-cause inpatient CAP.For elderly lung cancer patients aged ≥75 years, PPSV23 inoculated during anti-cancer treatment period could reduce CAP hospitalizations and improve survival.

Unexpected close surgical margin in resected buccal cancer: Very close margin and DAPK promoter hypermethylation predict poor clinical outcomes

OBJECTIVESnIn resected buccal cancer patients, an unexpected close surgical margin has been observed to correlate with poor clinical outcomes. However, close surgical margin alone does not independently guide post-operative therapies, revealing a clinical debate. Hence, the present study intended to explore epigenetic-based bio-predictors for further stratifying this debating patient population.nnnMATERIALS AND METHODSnBetween 2000 and 2008, we retrospectively recruited 44 resected buccal cancer patients with a close surgical margin of ≤5 mm. All patients had post-operative radiotherapy. Genomic DNA was extracted from tumor-enrich areas that contained cancer cells of >70%. Methylation-specific PCR was performed to detect promoter methylation of four tumor suppressor genes, including RASSF1A, DAPK, IRF8, and SFRP1. Post-irradiation locoregional control was defined as the primary end point.nnnRESULTSnThere were 40 males and 4 females, with a median age of 53.5 years (range, 32-82 years). Multivariate analysis identified two independent predictors for locoregional recurrence: very close margin of ≤1 mm (HR: 4.96; 95% CI, 1.63-15.09; P=0.018) and promoter hypermethylation of DAPK (HR: 2.83; 95% CI, 1.05-7.63; P=0.042). The highest risk of locoregional recurrence was observed in patients with both of the two factors (HR, 8.05; 95% CI, 2.56-25.82; P=0.002) when compared with patients with none. Shorter disease-free survival, but not overall survival, was also observed.nnnCONCLUSIONnMore aggressive managements should be considered in resected buccal cancer patients with both very close margin and DAPK promoter hypermethylation rather than post-operative observation or radiotherapy alone.

Leukemia Risk After Cardiac Fluoroscopic Interventions Stratified by Procedure Number, Exposure Latent Time, and Sex: A Nationwide Population-Based Case-Control Study.

AbstractA number of cardiac fluoroscopic interventions have increased rapidly worldwide over the past decade. Percutaneous transluminal coronary angioplasty (PTCA) and stent implantation have become increasingly popular, and these advancements have allowed patients to receive repetitive treatments for restenosis. However, these advancements also significantly increase radiation exposure that may lead to higher cumulative doses of radiation. In the present study, a nationwide population-based case-controlled study was used to explore the risk of leukemia after cardiac angiographic fluoroscopic intervention.A total of 5026 patients with leukemia and 100,520 control patients matched for age and sex (1:20) by a propensity score method without any cancer history were enrolled using the Registry Data for Catastrophic Illness and the National Health Insurance Research Database (NHIRD) of Taiwan between 2008 and 2010. All subjects were retrospectively surveyed (from year 2000) to determine receipt of cardiac fluoroscopic interventions. Data were analyzed using conditional logistic regression models, and estimated crude and adjusted odds ratios (95% confidence interval).After adjusting for age, gender, and comorbidities, PTCA was found to be associated with an increased risk of leukemia with an adjusted OR of 1.566 (95% CI, 1.282–1.912), whereas coronary angiography alone without PTCA and cardiac electrophysiologic study were not. Our results also showed that an increased frequency of PTCA and coronary angiography was associated with a higher risk of leukemia (adjusted OR: 1.326 to 1.530 [all Pu200a<u200a0.05]). Gender subgroup analyses demonstrated that men were associated with a higher risk of leukemia compared with women.These results provide additional data in the quantification of the long-term health effects of radiation exposure derived from the cardiac fluoroscopic diagnostic and therapeutic intervention. PTCA alone or PTCA with coronary angiography was associated with an elevated risk of leukemia. Continued follow-up of existing cohorts will be valuable to help assess lifetime risks of cancer.

Dose measurements for gamma knife with radiophotoluminescent glass dosemeter and radiochromic film

Stereotactic radiosurgery (SRS) is designed for patients with small lesion areas that are not suitable for actual surgery. SRS delivers high dose to the lesion with high gradient on the irradiation margin area. In this study, radiophotoluminescent glass dosemeter (RPLGD) and radiochromic film were used to measure the output factor of a gamma knife. Also, a Monte Carlo code (OMEGA/BEAM) was applied to simulate the output factor. For 14 and 8 mm sizes of helmet collimators, the variations of output factors determined with RPLGD, radiochromic film, the Monte Carlo code and Elekta were all within 0.5 %. When helmet collimator size was 4 mm, the output factors detected from RPLGD, radiochromic film and Monte Carlo simulation were all within 3.2 % when compared with Elekta. Taken together, RPLGD, radiochromic film and Monte Carlo simulation will be used as precise tools to measure the output factor of a gamma knife.

Effect of liver cirrhosis on metastasis in colorectal cancer patients: A nationwide population-based cohort study

OBJECTIVEnThe aim of this study is to evaluate the liver metastasis risk among colorectal cancer patients with liver cirrhosis.nnnMETHODSnThis was a nationwide population-based cohort study of 2973 newly diagnosed colorectal cancer patients with liver cirrhosis and 11 892 age-sex matched controls enrolled in Taiwan between 2000 and 2010. The cumulative risk by Kaplan-Meier method, hazard ratio by the multivariate Cox proportional model and the incidence density were evaluated.nnnRESULTSnThe median time interval from the colorectal cancer diagnosis to the liver metastasis event was 7.42 months for liver cirrhosis group and 7.67 months for non-liver cirrhosis group. The incidence density of liver metastasis was higher in the liver cirrhosis group (61.92/1000 person-years) than in the non-liver cirrhosis group (47.48/1000 person-years), with a significantly adjusted hazard ratio of 1.15 (95% CI = 1.04-1.28, P = 0.007). The 10-year cumulative risk of liver metastasis for the liver cirrhosis and the non-liver cirrhosis group was 27.1 and 23.6%, respectively (P = 0.006). For early cancer stage with locoregional disease patients receiving surgery alone without adjuvant anti-cancer treatments, patients with liver cirrhosis (10-year cumulative risk 23.9 vs. 15.7%, P < 0.001) or cirrhotic symptoms (10-year cumulative risk 25.6 vs. 16.6%, P = 0.009) both still had higher liver metastasis risk compared with their counterparts. For etiologies of liver cirrhosis, the 10-year cumulative risk for hepatitis B virus and hepatitis C virus, hepatitis B virus, hepatitis C virus, other causes and non-liver cirrhosis were 29.5, 28.9, 27.5, 26.7 and 23.4%, respectively, (P = 0.03).nnnCONCLUSIONSnOur study found that liver metastasis risk was underestimated and even higher in colorectal cancer patients with liver cirrhosis.

Everolimus sensitizes Ras-transformed cells to radiation in vitro through the autophagy pathway

Modern radiation therapy strives to minimize injury to organs while increasing the anticancer effects. The present study aimed to investigate the radiosensitizing effects of everolimus and to examine the molecular mechanisms responsible for everolimus‑mediated radiosensitization. Radiation in combination with everolimus (30 nM) sensitized Ras-transformed cells to radiation in vitro. Radiation induced apoptotic markers (sub-G1 cell accumulation, membrane inversion and DNA fragmentation) and treatment with everolimus did not promote radiation-induced apoptosis. However, LC3-II expression increased following combination treatment with everolimus and radiation, and the radiosensitizing effects of everolimus were reversed following transfection with small interfering RNA (siRNA) targeting Beclin 1. In addition, the protein levels of activated S6 kinase 1 (S6K1) were significantly reduced following treatment with everolimus, and the phosphorylation of factor 4E binding protein 1 (4EBP1) was suppressed following combination treatment. Taken together, our data demonstrate that everolimus sensitizes Ras-transformed cells to radiation in vitro. Everolimus-mediated radiosensitization is associated with the autophagy pathway. Thus, everolimus is a novel radiosensitizing agent with potential for use in cancer radiotherapy.