Prevalence and Associated Factors for Thyroid Dysfunction Among Patients On Targeted Therapy for Cancers: A Single-Center Study from Thailand.

Objective: This study aimed to explore the prevalence and associated factors of thyroid dysfunction among cancer patients treated with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). Methodology: A cross-sectional study was done in patients who received TKIs at Rajavithi Hospital in 2019. For patients treated with ICI, a retrospective chart review for patients seen in 2018 to 2019 was conducted. If there were abnormal thyroid function tests (TFT), thyroid autoantibodies were tested. Results: There were 144 patients on TKIs with a mean age of 56.0 years. Thyroid dysfunction was found in 14.6% of patients and most had subclinical hypothyroidism (n = 16, 11.1%). Imatinib (n = 11, 10.8%) and sunitinib (n = 4, 100%) were the 2 most common TKIs given to patients with thyroid dysfunction. Thyroid dysfunction was associated with male sex, chronic kidney disease and hepatitis B virus infection but not with previous thyroid disease and presence of thyroid autoantibodies.There were 18 patients who received ICIs. The mean age was 63.3 years. Twelve patients (66.7%) used programmed cell death protein-1 antibody (anti-PD1), mainly nivolumab. Thyroid dysfunction was found in 50%, which occurred at a median duration of 46 days. Most patients had overt hypothyroidism and 55.6% needed levothyroxine replacement. Conclusion: Thyroid dysfunctions from TKIs were mostly asymptomatic and mild in severity. Some types of TKIs might be associated with thyroid dysfunction. On the other hand, thyroid dysfunction from ICIs usually occurs within 6 months and requires levothyroxine replacement.

Efficacy of Combination Docetaxel and Nintedanib in Advanced Non-Small Cell Lung Cancer in Thailand: A Multicenter Study.

INTRODUCTION: The mainstay systemic treatment for non-oncogenic addictive advanced stage non-small cell lung cancer is chemotherapy. Anti-angiogenic agents are additive compounds that enhance disease control and lead to improvement of overall survival benefit. Recently PD-(L)1 blockage, a checkpoint inhibitor, has been adopted as another line of treatment. A sequential strategy to enhance the efficacy of combination docetaxel and nintedanib after immunotherapy, correlated with genomic mutation, has been explored. METHOD: A retrospective cohort study of 56 patients from 8 centers in Thailand who received combination docetaxel and nintedanib via the Thai nintedanib Named Patient Use program was conducted. Demographic characteristics, treatment details, and treatment responses were retrieved from medical records. RESULTS: The majority of patients were male (62.5%) with adenocarcinoma subtype (88%). Thirty-five percent had sensitizing EGFR mutation. Combination docetaxel and nintedanib was given as second to fourth line of treatment. Median PFS of docetaxel/nintedanib was 5.6 months [95% CI 4.8-6.9]. Median OS of the entire cohort was 22.5 months [95% CI 20.2-31.1]. Among them, only four patients received this combination after immunotherapy which limited the validity of efficacy analysis. Median PFS of those four patients was 7.9 months [range 5.2-9.1] which was slightly higher than the remaining cohort (median PFS 4.5 months, 95% CI: 4.0-6.0, p-value 0.09). Among the adenocarcinoma subtype, a relapse-time of platinum-doublet chemotherapy of more than 6 months was solely indicated as a benefit of combination docetaxel/nintedanib treatment compared to the relapse-time of platinum-doublet chemotherapy of less than 6 months by multivariate HR of PFS 0.32 [95% CI: 0.14-0.68, p-value 0.003]. CONCLUSION: Combination docetaxel and nintedanib provided more benefit in relapse-time of platinum-doublet chemotherapy of more than 6 months in advanced stage adenocarcinoma lung cancer. Neither EGFR nor ALK alteration influenced the outcome of treatment.

Timing of chronic obstructive pulmonary disease diagnosis in lung cancer prognosis: a clinical and genomic-based study.

BACKGROUND: A two-phase study (clinical and genomic-based) was conducted to evaluate the effect of timing of chronic obstructive pulmonary disease (COPD) diagnosis on lung cancer outcomes. METHODS: The prognostic influence of COPD was investigated in a clinical cohort of 1,986 patients who received surgery for stage I lung cancer; 823 (41.4%) of them also had COPD, including 549 (27.6%) incidental COPD (diagnosed within 6-months of lung cancer diagnosis) and 274 (13.8%) prior COPD (>6 months before lung cancer diagnosis). The genomic variations were analyzed from another cohort of 1,549 patients for association with 384 lung cancer-related single nucleotide polymorphisms (SNPs). RESULTS: Older age (≥70 years), smokers, and respiratory symptoms were independent predictors of incidental COPD in lung cancer (all P<0.05). Similar to prior COPD, incidental COPD increased postoperative complications and worsened quality-of-life related to dyspnea (both P<0.05). Multivariate Cox regression analysis showed lung cancer survival decreased significantly in incidental COPD (HR, 1.30; 95% CI, 1.02-1.66), but not in prior COPD (HR, 1.15; 95% CI, 0.87-1.52). Among prior COPD, median survival showed a trend for being better in those with fewer exacerbations (0-1 vs. ≥2 exacerbation/year; 6.1 vs. 4.1 years; P=0.10). The SNP-based analysis identified ADCY2:rs52827085 was significantly associated with risk of incidental COPD (OR, 1.76; 95% CI, 1.30-2.38) and NRXN1:rs1356888 associated with prior COPD complicated with lung cancer (OR, 1.73; 95% CI, 1.29-2.33). CONCLUSIONS: Different long-term survival and genomic variants were observed between lung cancer patients with incidental and with prior COPD, suggesting timing of COPD diagnosis should be considered in lung cancer clinical management and mechanistic research.

A randomized, double-blind, placebo-controlled study evaluating the efficacy of combination olanzapine, ondansetron and dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving doxorubicin plus cyclophosphamide.

BACKGROUND: Since most of Thai cancer patients receiving high emetogenic chemotherapy do not have access to neurokinin-1 (NK-1) receptor antagonists or palonosetron as recommended by international guidelines for chemotherapy-induced nausea and vomiting (CINV) prevention. We decided to evaluate the efficacy of olanzapine with the real-life practice antiemetic drugs ondansetron and dexamethasone, in prevention of CINV resulting from doxorubicin plus cyclophosphamide regimen in early-stage breast cancer patients. METHODS: In this randomized, double-blind, placebo-controlled trial, we compared olanzapine with a placebo in combination with ondansetron and dexamethasone in early-stage breast cancer patients receiving doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2. The intervention group received olanzapine 10 mg orally while the control group received a matching placebo daily on day 1 through day 4. All patients received ondansetron 8 mg and dexamethasone 20 mg intravenously 30 minutes before chemotherapy administration and then dexamethasone 10 mg daily orally from day 1 through day 4. The primary endpoint was no nausea rate in the early period. The secondary endpoints were no nausea rate in the delayed and overall periods and a complete response (no vomiting and no use of rescue drug). Outcomes were determined by patients' self-reported daily records of episodes of vomiting or retching, use of rescue therapy and daily levels of nausea based on a visual-analogue scale from the first cycle of chemotherapy. RESULTS: A total of 39 female patients were randomized in a 1:1 ratio to receive olanzapine (20 patients) or a matching placebo (19 patients). A significantly greater proportion of patients reported no nausea in the olanzapine group than in the placebo group in both the early period (0-24 hours after chemotherapy) and the overall period (0-120 hours after chemotherapy). Patients who reported no nausea in the early period accounted for 50% and 10.5% in the olanzapine group and in the placebo group respectively (P=0.008). In the overall period, 30.0% and 0% of patients reported no nausea in the olanzapine and placebo groups respectively (P=0.009). In the early period, there was a significantly different complete response rate between two treatment groups; 75.0% in the olanzapine group and 36.8% in the placebo group (P=0.016). Overall treatment-related adverse events were not significantly different between the two study groups except that somnolence was significantly more common in the olanzapine group than in the placebo group. CONCLUSIONS: Olanzapine 10 mg combined with ondansetron and dexamethasone was more effective than a placebo in preventing CINV resulting from doxorubicin plus cyclophosphamide in early-stage breast cancer patients, especially in the first 24 hours after chemotherapy administration. The short duration of olanzapine was safe and well tolerated.

Sarcomatoid Carcinoma of the Lung: The Mayo Clinic Experience in 127 Patients.

BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is an unusual form of non-small-cell lung cancer (NSCLC). Because of its rarity and heterogeneity, the treatment and prognosis of PSC have not been clearly described. METHODS AND MATERIALS: We retrospectively evaluated all patients with a diagnosis of PSC from 1997 to 2015 at the Mayo Clinic (Rochester, MN). The clinical characteristics, treatment details, and outcomes were collected. The survival rates of the PSC patients were compared with those for other subtypes of NSCLC. We used propensity score matching to minimize the bias resulting from to imbalanced comparison groups. RESULTS: The study included 127 PSC patients. The median age at diagnosis was 68 years (range, 32-89 years), most of whom were men (61%) and smokers (82%). The clinical stage was I, II, III, and IV in 15.9%, 20.6%, 22.2%, and 41.3%, respectively. The median survival time was 9.9 months (95% confidence interval [CI], 7.6-12.6 months). The 1-, 2-, and 5-year survival rates were 42%, 23%, and 15%, respectively. Most patients received multimodality treatment. Of the 3 patients who received neoadjuvant chemotherapy, a partial response was demonstrated in 2. Twenty-five patients who underwent palliative chemotherapy were evaluated for tumor response: 52% experienced progression, 40% stable disease, 8.0% a partial response, and 0% a complete response. Multivariate analysis showed T stage, M stage, and treatment with surgery plus neoadjuvant chemotherapy or surgery plus adjuvant therapy were independent prognostic factors (P < .05). In matched analysis, multivariate models revealed worse overall survival for PSC compared with adenocarcinoma (hazard ratio, 2.38; 95% CI, 1.61-2.53) and squamous cell carcinoma (hazard ratio, 2.20; 95% CI, 1.44-2.34). CONCLUSION: We found the outcome of PSC to be significantly worse than that of adenocarcinoma and squamous cell carcinoma. Neoadjuvant or adjuvant chemotherapy, in addition to surgical resection, should be considered.

Survival and Prognostic Factors of Metastatic Breast Cancer.

Background: Prognostic factors for survival of metastatic breast cancer (MBC) patients are important for identifying risks and deciding on patient treatment; however, few studies of prognostic factors in MBC have been performed in Thailand. Objective: To determine the survival duration and prognostic factors for overall survival in metastatic breast cancer. Material and Method: This retrospective cohort study was conducted by reviewing 232 files of MBC patients treated in the Oncology Unit, Department of Medicine, Rajavithi Hospital from January 1st 2005 to December 31th 2013. Results: There were 232 patients whose median age was 51.5 years. The 1-year, 3-year and 5-year overall survival rates for MBC patients were 53.2%, 18.7% and 7.3% respectively, and the median overall survival time of all MBC patients was 13.43 months. Multivariate analysis showed that large tumor size T4 (HR = 1.89, 95% CI 1.04-3.44; p = 0.038), ECOG performance status 3-4 (HR = 2.44, 95% CI 1.48-4.00; p<0.001) and treatment with best supportive care only (HR = 5.95, 95% CI 3.56-9.96; p<0.001) were significant prognostic factors for poor overall survival in MBC. Breast cancer subtype analysis showed that luminal-A subtype was associated with a high rate of late recurrence (beyond 2 years) (p = 0.016) and HER-2 enriched subtype was related to a high rate of early relapse (before 2 years (p = 0.001)). Conclusion: The important prognostic factors for overall survival in MBC were tumor size, ECOG PS and type of first-line treatment. In order to improve survival outcomes, patients with large tumor size should be treated with intensive chemotherapy and targeted therapy if HER-2 status positive. It is essential that early breast cancer patients have an awareness of recurrent diseases in order to identify good performance status in MBC patients suitable for active treatment.

Hepatitis C infection and renal cell carcinoma: A systematic review and meta-analysis.

AIM: To investigate the association between hepatitis C virus (HCV) infection and risk of renal cell carcinoma (RCC). METHODS: A literature search was performed from inception until February 2016. Studies that reported relative risks, odd ratios, hazard ratios or standardized incidence ratio comparing the risk of RCC among HCV-infected participants vs those without HCV infection were included. Participants without HCV infection were used as comparators. Pooled odds ratios and 95%CI were calculated using a random-effect, generic inverse variance method. RESULTS: Seven observational studies were with 196826 patients were included in the analysis to assess the risk of RCC in patients with HCV. A significantly increased risk of RCC among participants with HCV infection was found with a pooled RR of 1.86 (95%CI: 1.11-3.11). The association between RCC and HCV was marginally insignificant after a sensitivity analysis limited only to studies with adjusted analysis, with a pooled RR of 1.50 (95%CI: 0.93-2.42). CONCLUSION: Our study demonstrated a potential association between HCV infection and RCC. Further studies of RCC surveillance in patients with HCV are required.

Factors influencing development and mortality of acute respiratory failure in hospitalized patient with active pulmonary tuberculosis: a 10-year retrospective review.

BACKGROUND: Pulmonary tuberculosis with acute respiratory failure is fatal and is a burden in the intensive care units and leads to mortality. This retrospective study identifies the factors influencing the development of pulmonary tuberculosis requiring mechanical ventilation (TBMV) and mortality in the hospitalized patients with pulmonary tuberculosis. METHODS: The medical records of hospitalized adult patients with pulmonary tuberculosis were retrospectively reviewed. Demographic data, clinical presentations, radiographic findings, biochemical tests, and clinical outcomes were collected. Data were compared by Student's t-test and Chi-square test between groups. Select variables that were statistically significant with P values <0.1 were introduced into a forward, stepwise, logistic regression model. Odds ratios (ORs) and their 95% confidence intervals (CIs) identified the independent influencing factors in the development of TBMV and mortality. RESULTS: Of 268 enrolled patients, 185 (69.0%) were male. The patients were equally divided between the TBMV and non-TBMV groups. The shorter duration of illness (OR, 0.99; 95% CI, 0.98-0.99), underlying disease of AIDS (OR, 14.55; 95% CI, 1.71-123.91), presentation of fever (OR, 2.11; 95% CI, 1.20-3.71) and dyspnea (OR, 3.51; 95% CI, 2.02-6.11), large amount of acid fast bacilli on sputum smear (OR, 3.76; 95% CI, 1.90-7.47), lower serum albumin level (OR, 0.39; 95% CI, 0.26-0.59), and delayed initiation of anti-tuberculosis agents (OR, 1.06; 95% CI, 1.00-1.12) were independent factors to develop TBMV. Male gender (OR, 2.16; 95% CI, 1.01-4.61), consolidation pattern on chest X-ray (OR, 2.41; 95% CI, 1.17-4.98), and lower serum albumin (OR, 0.39; 95% CI, 0.21-0.71) were correlated to mortality. CONCLUSIONS: The incidence and mortality rate of TBMV patients were high. Acute tuberculous pneumonia, underlying disease of AIDS, amount of acid fast bacilli, and delayed administration of anti-tuberculosis agents were independent risk factors to develop TBMV. Male gender, consolidation on chest X-ray, and low serum albumin were significantly related to mortality.