Chia Lun Chang

Curative-Intent Aggressive Treatment Improves Survival in Elderly Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma and High Comorbidity Index.

AbstractFor locally advanced head and neck squamous cell carcinoma (HNSCC), therapeutic decisions depend on comorbidity or age. We estimated the treatment outcomes of patients with different Charlson comorbidity index (CCI) scores and ages to determine whether aggressive treatment improves survival.Data from the Taiwan National Health Insurance and cancer registry databases were analyzed, and we included >20-year-old patients with American Joint Committee on Cancer (AJCC) stage III or IV HNSCC (International Classification of Diseases, Ninth Revision, Clinical Modification codes 140.0–148.9) undergoing surgery, chemotherapy (CT), radiotherapy (RT), concurrent chemoradiotherapy (CCRT), sequential CT and RT, or surgery with adjuvant treatment. The exclusion criteria were a past cancer history, distant metastasis, AJCC stage I or II, missing sex data, an age < 20 years, nasopharyngeal cancer, in situ carcinoma, sarcoma, and HNSCC recurrence. The index date was the date of first HNSCC diagnosis, and comorbidities were scored using the CCI. The enrolled patients were categorized into Group 1 (curative-intent aggressive treatments) and Group 2 (best supportive care or palliative treatments).We enrolled 21,174 stage III or IV HNSCC patients without distant metastasis (median follow-up, 3.25 years). Groups 1 and 2 comprised 18,584 and 2232 patients, respectively. After adjustment for age, sex, and clinical stage, adjusted hazard ratios (95% confidence intervals) of overall death in Group 1 were 0.33 (0.31–0.35), 0.34 (0.31–0.36), and 0.37 (0.28–0.49), and those of all-cause death among patients undergoing curative surgical aggressive treatments were 1.13 (0.82–1.55), 0.67 (0.62–0.73), and 0.49 (0.46–0.53) for CCI scores of ≥10, 5 to 9, and <5, respectively.Aggressive treatments improve survival in elderly (≥65 years) and critically ill HNSCC patients. Curative nonsurgical aggressive treatments including definitive RT or CCRT might be suitable for HNSCC patients with CCI scores ≥10.

Outcomes of Induction Chemotherapy for Head and Neck Cancer Patients: A Combined Study of Two National Cohorts in Taiwan.

AbstractThe use of induction chemotherapy (CT) is controversial. We compared the survival of head and neck cancer patients receiving docetaxel- or platinum-based induction CT before concomitant chemoradiotherapy (CCRT) with the survival of those receiving upfront CCRT alone.Data from the National Health Insurance and cancer registry databases in Taiwan were linked and analyzed. We enrolled patients who had head and neck cancer between January 1, 2002 and December 31, 2011. Follow-up was from the index date to December 31, 2013. We included head and neck patients diagnosed according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes 140.0–148.9 who were aged >20 years, at American Joint Committee on Cancer clinical cancer stage III or IV, and receiving induction CT or platinum-based CCRT. The exclusion criteria were a cancer history before head and neck cancer diagnosis, distant metastasis, AJCC clinical cancer stage I or II, receipt of platinum and docetaxel before radiotherapy, an age <20 years, missing sex data, docetaxel use during or after RT, induction CT for >8 weeks before RT, induction CT alone before RT, cetuximab use, adjuvant CT within 90 days after RT completion, an RT dose <7000 cGy, curative head and neck cancer surgery before RT, nasopharyngeal cancer, in situ carcinoma, sarcoma, and head and neck cancer recurrence.We enrolled 10,721 stage III–IV head and neck cancer patients, with a median follow-up of 4.18 years (interquartile range, 3.25 years). The CCRT (arm 1), docetaxel-based induction CT (arm 2), and platinum-based CCRT (arm 3; control arm) groups comprised 7968, 503, and 2232 patients, respectively. Arm 3 was used to investigate mortality risk after induction CT. After adjustment for age, sex, clinical stage, and comorbidities, the adjusted hazard ratios (aHRs) (95% confidence interval [CI]) for overall death were 1.37 (1.22–1.53) and 1.44 (1.36–1.52) in arms 2 and 3, respectively. In a disease-specific survival rate analysis, aHRs (95% CI) of head and neck cancer-related death were 1.29 (1.14–1.46) and 1.47 (1.38–1.56) in arms 2 and 3, respectively.Compared with CCRT alone, docetaxal- or platinum-based induction CT did not improve survival but increased the risk of all-cause and head and neck cancer-related death.

Effectiveness of esophagectomy in patients with thoracic esophageal squamous cell carcinoma receiving definitive radiotherapy or concurrent chemoradiotherapy through intensity-modulated radiation therapy techniques.

Few large, prospective, randomized studies have investigated the effectiveness of esophagectomy in patients with thoracic esophageal squamous cell carcinoma (TESCC) who receive definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) through modern, intensity modulated‐RT (IMRT) techniques. The therapeutic effects of esophagectomy in patients with TESCC were evaluated using modern clinical staging and RT techniques and suitable RT doses.

Statins improve outcomes of nonsurgical curative treatments in hepatocellular carcinoma patients.

AbstractStatins are associated with a reduced risk of hepatocellular carcinoma (HCC) and have the potential to be an adjuvant agent for HCC. In this study, we examined whether statin use is associated with additional benefits among patients who received curative treatments (CTs) such as surgery, percutaneous ethanol injection (PEI), and radiofrequency ablation (RFA).We conducted a cohort study using the Taiwan National Health Insurance Research Data linked to the Taiwan Cancer Registry in 2001 to 2012. The patient cohort consisted of those who received different treatments, and we compared patients who received statins with those who did not. Statin users were defined as patients who received >28 cumulative defined daily doses after their HCC diagnosis. We used a time-dependent Cox proportional method to model the time from the HCC diagnosis to any death and HCC death between men who received statins and those who did not after adjusting for confounders. Data on statin prescriptions were collected every 6 months to define the user status.In total, 18,892 patients were included, and the mean follow-up duration was 1.74 years. The adjusted hazard ratio (aHR) of all-cause deaths increased in HCC patients who received RFA/PEI compared to those who received surgery (P < 0.0001 and P < 0.05, with aHRs of 1.81 and 1.16, respectively, for hepatitis B virus [HBV] or non-HBV HCC). However, with the addition of statin use to RFA or PEI, the overall survival was statistically equal.Surgical resection is still superior over other therapies. If HCC patients cannot meet the criteria for surgery, the addition of statin use to RFA or PEI might improve HCC survival.

Dose escalation intensity-modulated radiotherapy-based concurrent chemoradiotherapy is effective for advanced-stage thoracic esophageal squamous cell carcinoma

PURPOSE No studies have investigated the effects of irradiation-dose escalation intensity-modulated radiotherapy (IMRT)-based concurrent chemoradiotherapy (CCRT) in patients with thoracic esophageal squamous cell carcinoma (TESCC). PATIENTS AND METHODS We analyzed data from patients with TESCC who were enrolled in the Taiwan Cancer Registry database. To compare treatment outcomes, the patients were categorized into two groups according to their radiotherapy doses: group 1, who received CCRT<60Gy with IMRT, and group 2, who received CCRT≥60Gy with IMRT. Group 1 was used as the control for investigating posttreatment mortality risk. RESULTS We enrolled 2061 patients with TESCC without distant metastasis who received CCRT with IMRT. Multivariate Cox regression analysis indicated that advanced clinical American Joint Committee on Cancer (AJCC) stage (≥IIIA), alcohol consumption, and cigarette smoking were significant, poor independent predictors in patients with TESCC receiving IMRT-based CCRT. IMRT-based CCRT (≥60Gy; adjusted hazard ratio [aHR]: 0.75; 95% confidence interval [CI]: 0.63-0.83) was a significant independent prognostic factor for overall survival (P<0.0001). After adjustment for confounders, the aHRs (95% CIs) for overall mortality at all clinical stages were 0.75 (0.68-0.83, P<0.0001) in group 2. In group 2, the aHRs (95% CIs) for overall mortality at early (IA-IIB) and advanced (IIIA-IIIC) AJCC clinical stages were 0.89 (0.70-1.04, P=0.1905) and 0.75 (0.67-0.83, P<0.0001), respectively. CONCLUSION Compared with standard-dose IMRT-based CCRT, high-dose IMRT-based CCRT yields more favorable survival outcomes in patients with advanced-stage TESCC.

High‐dose or low‐dose cisplatin concurrent with radiotherapy in locally advanced head and neck squamous cell cancer

No randomized studies have compared low‐dose or high‐dose concurrent chemoradiotherapy (CRT).

Dementia Risk in Irradiated Patients with Head and Neck Cancer

AbstractPatients with head and neck cancer are treated through surgery, radiotherapy (RT), and chemotherapy (CT). Carotid artery damage and neurotoxicity were previously observed in these patients. This study estimated the dementia risk associated with different treatment modalities in a head and neck cancer population with long-term follow-up.Taiwans National Health Insurance claims database and a cancer registry database from the Collaboration Center of Health Information Application were linked for the present analysis. Patients with head and neck cancer, treated from January 1, 2002 to December 31, 2010, were included in the study. The follow-up duration was the period from the index date to December 31, 2012. Inclusion criteria were head and neck cancer; an age >20 years; and having undergone surgery, CT, concurrent CT, or surgery with adjuvant treatment. Exclusion criteria were another cancer diagnosed before the head and neck cancer, death or being diagnosed with dementia within 2 years after the treatment of the head and neck cancer, stroke before the index date, distant metastasis, in situ carcinoma, sarcoma, head and neck cancer recurrence, an unknown sex, and an age <20 years. In total, 20,135 patients were included.In patient groups that underwent surgery alone, surgery and adjuvant chemoradiotherapy, and chemoradiotherapy alone, the dementia incidence per 1000 person-years was 1.44, 1.04, and 1.98, respectively. The crude hazard ratio (HR) of dementia was 1.84 (95% confidence interval [CI] 1.21–2.81) in the RT with or without CT group. After adjustment for age, sex, clinical stage, and comorbidity, the HR was 1.92 (95% CI 1.14–3.24). Examining the dementia risk in patients who received different treatment modalities according to the Cox proportional-hazard model revealed that an age >65 years and having undergone RT with or without CT were risk factors (P < 0.001 and P = 0.015; and HRs of 16.5 and 1.92, respectively). The dementia risk in patients at different clinical stages was not significantly different among the various treatment groups, regardless of whether the patients received RT. However, younger (<65 y) patients who received RT with or without CT had a 2.96-fold (95% CI 1.24–7.08) higher risk of dementia and a 3.54-fold (95% CI 1.32–9.51) higher adjusted HR compared with the surgery-alone group. Patients who received a total radiation dose >6660 cGy exhibited a 1.69-fold (95% CI 0.97–2.95, P = 0.063) higher dementia risk compared with those who received a total radiation dose <6660 cGy.Receiving a higher radiation dose increased the dementia risk and persistently escalated the dementia incidence even 9 years after RT. Younger (<65 y) patients have a high risk of dementia after RT. The selection of young patients for dose de-escalation requires improvement for reducing irradiation to the neck and areas near brain tissues, particularly in Taiwan, where the median patient age is 53 years.

Survival prognostic factors for metachronous second primary head and neck squamous cell carcinoma.

We examined the overall survival rates of a national cohort to determine optimal treatments and prognostic factors for patients with metachronous second primary head and neck squamous cell carcinomas (mspHNSCCs) at different stages and sites. We analyzed data of mspHNSCC patients collected from the Taiwan Cancer Registry database. The patients were categorized into four groups based on the treatment modality: Group 1 (control arm; chemotherapy [CT] alone), Group 2 (reirradiation [re‐RT] alone with intensity‐modulated radiotherapy [IMRT]), Group 3 (concurrent chemoradiotherapy alone [irradiation with IMRT]), and Group 4 (salvage surgery with or without RT or CT). We enrolled 1741 mspHNSCC patients without distant metastasis. Multivariate Cox regression analyses revealed that Charlson comorbidity index (CCI) ≥6, stage of second HNSCC, stage of first HNSCC, and duration from first primary HNSCC of <3 years were significant poor independent prognostic risk factors for overall survival. After adjustment, adjusted hazard ratios and 95% confidence intervals for the overall all‐cause mortality risk at mspHNSCC clinical stages III and IV were 0.72 (0.40–1.82), 0.52 (0.35–0.75), and 0.32 (0.22–0.45) in Groups 2, 3, and 4, respectively. A Cox regression analysis indicated that a re‐RT dose of ≥6000 cGy was an independent protective prognostic factor for treatment modalities. CCI ≥ 6, stage of second HNSCC, stage of first HNSCC, and duration from first primary HNSCC of <3 years were significant poor independent prognostic risk factors for overall survival. A re‐RT dose of ≥6000 cGy may be necessary for mspHNSCCs.

Statin-based palliative therapy for hepatocellular carcinoma

Abstract Most hepatocellular carcinoma (HCC) patients worldwide do not receive curative treatments. Alternative treatments for most HCC patients include palliative treatments, such as transarterial chemoembolization (TACE), chemotherapy, and radiotherapy. Although statins may be a chemopreventive treatment option for reducing hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related HCC risks, their therapeutic effects are unknown. This study evaluated the effects of statin on HCC patients receiving palliative treatment. Data from the National Health Insurance claims database and cancer registry databases of The Collaboration Center of Health Information Application, Taiwan, were analyzed. We included HCC patients who were treated between January 1, 2001, and December 31, 2010, and followed them from the index date to December 31, 2012. The inclusion criteria were presence of HBV carrier-related HCC, age >20 years, and having received TACE, radiotherapy, or chemotherapy as palliative treatment. The exclusion criteria were cancer diagnosis before HCC was confirmed, surgery, liver transplantation, radiofrequency ablation, or percutaneous ethanol injection as curative treatment, missing sex-related information, HCC diagnosis before HBV, and age <20 years. We enrolled 20,200 HCC patients. The median follow-up duration was 1.66 years (interquartile range, 0.81). In total, 1988 and 18,212 patients received palliative treatment with and without statin use, respectively. HCC patients who received palliative treatment with statin use had lower HCC-specific deaths in all stages than those who received palliative treatment without statin use (P = 0.0001, 0.0002, 0.0012, and 0.0002, and relative risk (RR) = 0.763, 0.775, 0.839, and 0.718, for stages I–IV, respectively). In all-cause and HCC-specific deaths, decreasing trends (P for trend <0.0001) of adjusted hazard ratios (aHRs) were observed in all stages with no treatment, statin use only, palliative treatment only, and palliative treatment plus statin use. The aHRs of all-cause and HCC-specific deaths increased with the progress in cancer stage and reduced with the use of advanced therapeutic modalities (P for trend <0.0001). Differences in HBV- and non-HBV-related HCC were solely due to statin use. Statin use alone reduced HCC-specific deaths by 36% in non-HBV-related HCC in stage I and 50% in HBV-related HCC in stages II and III. With a relatively substantial reduction in mortality, the therapeutic effects of statin use were stronger in HBV-related HCC than in non-HBV-related HCC. Palliative treatments are critical for HCC patients. Multiple therapeutic methods with statin use reduced the mortality risk. Statins prolong the survival of patients with advanced HCC receiving palliative treatment, thus demonstrating its therapeutic value as an adjuvant treatment. Furthermore, statin-based palliative treatment in early stage HCC remarkably reduced the number of deaths. For patients who cannot tolerate palliative treatments, statin use only might possibly reduce mortality, particularly in HBV-related early stage HCC patients (>50% reduction in HCC deaths).

Value and application of trimodality therapy or definitive concurrent chemoradiotherapy in thoracic esophageal squamous cell carcinoma

Few large, prospective, randomized studies have investigated the value and optimal application of neoadjuvant chemoradiotherapy followed by surgery (trimodality therapy) or definitive concurrent chemoradiotherapy (CCRT) for patients with thoracic esophageal squamous cell carcinoma (TESCC).