Identification and overcoming rituximab resistance in diffuse large B-cell lymphoma using next-generation sequencing

Background/Aims@#Although rituximab, an antiCD20 monoclonal antibody, has dramatically improved the clinical outcomes of diffuse large B-cell lymphoma, rituximab resistance remains a challenge. @*Methods@#We developed a rituximab-resistant cell line (RRCL) by sequential exposure to gradually increasing concentrations of rituximab in a rituximab-sensitive cell line (RSCL). When the same dose of rituximab was administered, RRCL showed a smaller decrease in cell viability and apoptosis than RSCL. To determine the differences in gene expression between RSCL and RRCL, we performed next-generation sequencing. @*Results@#In total, 1,879 differentially expressed genes were identified, and in the over-representation analysis of Consensus-PathDB, mitogen-activated protein kinase (MAPK) signaling pathway showed statistical significance. MAPK13, which encodes the p38δ protein, was expressed more than four-fold in RRCL. Western blot analysis revealed that phosphop38 expression mainwas increased in RRCL, and when p38 inhibitor was administered, phosphop38 expression was significantly decreased. Therefore, we hypothesized that p38 MAPK activation was associated with rituximab resistance. Previous studies have suggested that p38 is associated with NF-κB activation. Deferasirox has been reported to inhibit NF-κB activity and suppress phosphorylation of the MAPK pathway. Furthermore, it also has cytotoxic effects on various cancers and synergistic effects in overcoming drug resistance. In this study, we confirmed that deferasirox induced dose-dependent cytotoxicity in both RSCL and RRCL, and the combination of deferasirox and rituximab showed a synergistic effect in RRCL at all combination concentrations. @*Conclusions@#We suggest that p38 MAPK, especially p38δ, activation is associated with rituximab resistance, and deferasirox may be a candidate to overcome rituximab resistance.

Long-Term Changes in the Mortality Rates of Thyroid Cancer in Korea: Analysis of Korean National Data from 1985 to 2020

Background@#Thyroid cancer mortality has been largely overlooked as relatively stable given the large gap between thyroid cancer incidence and mortality. This study evaluated long-term trends in age-standardized mortality rates (ASMRs) throughout Korea and compared them with mortality data reported by the Surveillance, Epidemiology, and End Results (SEER). @*Methods@#Cancer-specific mortality data from 1985 to 2020 were obtained from Statistics Korea. ASMRs from thyroid cancer were calculated based on the Korean mid-year resident registration population of 2005. We assessed SEER*Explorer and downloaded the mortality data. @*Results@#The ASMR increased from 0.19 to 0.77/100,000 between 1985 and 2002 but decreased continuously to 0.36/100,000 in 2020. The annual percent change (APC) in the ASMR between 1985 and 2003 and between 2003 and 2020 was 6.204 and −4.218, respectively, with similar patterns observed in both men and women. The ASMR of the SEER showed a modest increase from 1988 to 2016 and then stabilized. In subgroup analysis, the ASMR of the old age group (≥55 years) increased significantly from 0.82 in 1985 to 3.92/100,000 in 2002 (APC 6.917) but then decreased again to 1.86/100,000 in 2020 (APC −4.136). ASMRs according to the age group in the SEER showed a relatively stable trend even in the elderly group. @*Conclusion@#The ASMR of thyroid cancer in Korea had increased from 1985 to 2002 but has since been steadily decreasing. This trend was mainly attributed to elderly people aged 55 or over. The absolute APC value of Korea was much higher than that of the SEER.

Composite follicular lymphoma and classic Hodgkin lymphoma

Composite lymphoma is very rare and a combination of Hodgkin lymphoma and non-Hodgkin lymphoma and even histiocytic tumors can occur. Because of the unfamiliarity, not only can this cause diagnostic problems, but can also affect treatment plan. We report a case of composite lymphoma in a 40-year-old male. Initial biopsy showed a composite lymphoma of follicular lymphoma grade 1 and classic Hodgkin lymphoma. After chemotherapy, another lymph node was taken because of disease progression, which revealed follicular lymphoma, grade 3a without Hodgkin lymphoma component.

Preclinical Models of Follicular Cell-Derived Thyroid Cancer: An Overview from Cancer Cell Lines to Mouse Models

The overall prognosis of thyroid cancer is excellent, but some patients have grossly invasive disease and distant metastases with limited responses to systemic therapies. Thus, relevant preclinical models are needed to investigate thyroid cancer biology and novel treatments. Different preclinical models have recently emerged with advances in thyroid cancer genetics, mouse modeling and new cell lines. Choosing the appropriate model according to the research question is crucial to studying thyroid cancer. This review will discuss the current preclinical models frequently used in thyroid cancer research, from cell lines to mouse models, and future perspectives on patient-derived and humanized preclinical models in this field.

Immunoglobulin G4-Related Thyroid Disease: A Single-Center Experience and Literature Review

Background@#Immunoglobulin G4 (IgG4)-related disease is an entity that can involve the thyroid gland. The spectrum of IgG4-related thyroid disease (IgG4-RTD) includes Hashimoto thyroiditis (HT) and its fibrotic variant, Riedel thyroiditis, as well as Graves’ disease. The early diagnosis of IgG4-RTD is important because it is a medically treatable disease, and a delay in the diagnosis might result in unnecessary surgery. We present a case series of IgG4-RTD with a review of the literature. @*Methods@#We retrospectively reviewed the clinical presentation and the radiological and pathological findings of patients diagnosed with IgG4-RTD between 2017 and 2021 at a tertiary medical center in Korea. We also conducted a literature review of IgG4-RTD. @*Results@#Five patients were diagnosed with IgG4-RTD during the study period. The patients’ age ranged from 31 to 76 years, and three patients were men. Most patients visited the clinic for a neck mass, and hypoechogenic nodular lesions were observed on neck ultrasonography. Three patients had IgG4 HT, and two patients had IgG4 Riedel thyroiditis. All patients developed hypothyroidism that necessitated L-thyroxine replacement. The diagnosis of IgG4-RTD was confirmed after a pathological examination of the surgical specimen in the first two cases. However, the early diagnosis was possible after a core needle biopsy in three clinically suspected patients. @*Conclusion@#The diagnosis of IgG4-RTD requires clinical suspicion combined with serology and histological analyses using IgG4 immunostaining. The early diagnosis of IgG4-RTD is difficult; thus, biopsy with IgG4 immunostaining and serum IgG4 measurements will help diagnose patients suspected of having IgG4-RTD.

Active Surveillance as an Effective Management Option for Low-Risk Papillary Thyroid Microcarcinoma

Active surveillance (AS) for low-risk papillary thyroid microcarcinoma (PTMC) has been accepted worldwide as safe and effective. Despite the growing acceptance of AS in the management of low-risk PTMCs, there are barriers to AS in real clinical settings, and it is important to understand and establish appropriate AS protocol from initial evaluation to follow-up. PTMC management strategies should be decided upon after careful consideration of patient and tumor characteristics by a multidisciplinary team of thyroid cancer specialists. Patients should understand the risks and benefits of AS, participate in decision-making and follow structured monitoring strategies. In this review, we discuss clinical outcomes of AS from previous studies, optimal indications and follow-up strategies for AS, and unresolved questions about AS.

Protocol for a Korean Multicenter Prospective Cohort Study of Active Surveillance or Surgery (KoMPASS) in Papillary Thyroid Microcarcinoma

Background@#A Korean Multicenter Prospective cohort study of Active Surveillance or Surgery (KoMPASS) for papillary thyroid microcarcinomas (PTMCs) has been initiated. The aim is to compare clinical outcomes between active surveillance (AS) and an immediate lobectomy for low-risk PTMCs. We here outline the detailed protocol for this study. @*Methods@#Adult patients with a cytopathologically confirmed PTMC sized 6.0 to 10.0 mm by ultrasound (US) will be included. Patients will be excluded if they have a suspicious extra-thyroidal extension or metastasis of a PTMC or multiple thyroid nodules or other thyroid diseases which require a total thyroidectomy. Printed material describing the prognosis of PTMCs, and the pros and cons of each management option, will be provided to eligible patients to select their preferred intervention. For the AS group, thyroid US, thyroid function, and quality of life (QoL) parameters will be monitored every 6 months during the first year, and then annually thereafter. Disease progression will be defined as a ≥3 mm increase in maximal diameter of a PTMC, or the development of new thyroid cancers or metastases. If progression is detected, patients should undergo appropriate surgery. For the lobectomy group, a lobectomy with prophylactic central neck dissection will be done within 6 months. After initial surgery, thyroid US, thyroid function, serum thyroglobulin (Tg), anti-Tg antibody, and QoL parameters will be monitored every 6 months during the first year and annually thereafter. Disease progression will be defined in these cases as the development of new thyroid cancers or metastases. @*Conclusion@#KoMPASS findings will help to confirm the role of AS, and develop individualized management strategies, for low-risk PTMCs.

Gender-Dependent Reference Range of Serum Calcitonin Levels in Healthy Korean Adults

Background@#Serum calcitonin measurement contains various clinical and methodological aspects. Its reference level is wide and unclear despite sensitive calcitonin kits are available. This study aimed to identify the specific reference range in the healthy Korean adults. @*Methods@#Subjects were ≥20 years with available calcitonin (measured by a two-site immunoradiometric assay) data by a routine health checkup. Three groups were defined as all eligible subjects (group 1, n=10,566); subjects without self or family history of thyroid disease (group 2, n=5,152); and subjects without chronic kidney disease, autoimmune thyroid disease, medication of proton pump inhibitor/H2 blocker/steroid, or other malignancies (group 3, n=4,638). @*Results@#This study included 6,341 male and 4,225 female subjects. Males had higher mean calcitonin than females (2.3 pg/mL vs. 1.9 pg/mL, P<0.001) in group 1. This gender difference remained similar in groups 2 and 3. Calcitonin according to age or body mass index was not significant in both genders. Higher calcitonin in smoking than nonsmoking men was observed but not in women. Sixty-nine subjects had calcitonin higher than the upper reference limit (10 pg/mL) and 64 of them had factors associated with hypercalcitoninemia besides medullary thyroid cancer. Our study suggests the reference intervals for men who were non, ex-, current smokers, and women (irrespective of smoking status) as <5.7, <7.1, <7.9, and <3.6 pg/mL, respectively. @*Conclusion@#Specific calcitonin reference range should be provided considering for sex and smoking status. Taking account for several factors known to induce hypercalcitoninemia can help interpret the gray zone of moderately elevated calcitonin.

Active Surveillance as an Effective Management Option for Low-Risk Papillary Thyroid Microcarcinoma

Active surveillance (AS) for low-risk papillary thyroid microcarcinoma (PTMC) has been accepted worldwide as safe and effective. Despite the growing acceptance of AS in the management of low-risk PTMCs, there are barriers to AS in real clinical settings, and it is important to understand and establish appropriate AS protocol from initial evaluation to follow-up. PTMC management strategies should be decided upon after careful consideration of patient and tumor characteristics by a multidisciplinary team of thyroid cancer specialists. Patients should understand the risks and benefits of AS, participate in decision-making and follow structured monitoring strategies. In this review, we discuss clinical outcomes of AS from previous studies, optimal indications and follow-up strategies for AS, and unresolved questions about AS.

Protocol for a Korean Multicenter Prospective Cohort Study of Active Surveillance or Surgery (KoMPASS) in Papillary Thyroid Microcarcinoma

Background@#A Korean Multicenter Prospective cohort study of Active Surveillance or Surgery (KoMPASS) for papillary thyroid microcarcinomas (PTMCs) has been initiated. The aim is to compare clinical outcomes between active surveillance (AS) and an immediate lobectomy for low-risk PTMCs. We here outline the detailed protocol for this study. @*Methods@#Adult patients with a cytopathologically confirmed PTMC sized 6.0 to 10.0 mm by ultrasound (US) will be included. Patients will be excluded if they have a suspicious extra-thyroidal extension or metastasis of a PTMC or multiple thyroid nodules or other thyroid diseases which require a total thyroidectomy. Printed material describing the prognosis of PTMCs, and the pros and cons of each management option, will be provided to eligible patients to select their preferred intervention. For the AS group, thyroid US, thyroid function, and quality of life (QoL) parameters will be monitored every 6 months during the first year, and then annually thereafter. Disease progression will be defined as a ≥3 mm increase in maximal diameter of a PTMC, or the development of new thyroid cancers or metastases. If progression is detected, patients should undergo appropriate surgery. For the lobectomy group, a lobectomy with prophylactic central neck dissection will be done within 6 months. After initial surgery, thyroid US, thyroid function, serum thyroglobulin (Tg), anti-Tg antibody, and QoL parameters will be monitored every 6 months during the first year and annually thereafter. Disease progression will be defined in these cases as the development of new thyroid cancers or metastases. @*Conclusion@#KoMPASS findings will help to confirm the role of AS, and develop individualized management strategies, for low-risk PTMCs.

Gender-Dependent Reference Range of Serum Calcitonin Levels in Healthy Korean Adults

Background@#Serum calcitonin measurement contains various clinical and methodological aspects. Its reference level is wide and unclear despite sensitive calcitonin kits are available. This study aimed to identify the specific reference range in the healthy Korean adults. @*Methods@#Subjects were ≥20 years with available calcitonin (measured by a two-site immunoradiometric assay) data by a routine health checkup. Three groups were defined as all eligible subjects (group 1, n=10,566); subjects without self or family history of thyroid disease (group 2, n=5,152); and subjects without chronic kidney disease, autoimmune thyroid disease, medication of proton pump inhibitor/H2 blocker/steroid, or other malignancies (group 3, n=4,638). @*Results@#This study included 6,341 male and 4,225 female subjects. Males had higher mean calcitonin than females (2.3 pg/mL vs. 1.9 pg/mL, P<0.001) in group 1. This gender difference remained similar in groups 2 and 3. Calcitonin according to age or body mass index was not significant in both genders. Higher calcitonin in smoking than nonsmoking men was observed but not in women. Sixty-nine subjects had calcitonin higher than the upper reference limit (10 pg/mL) and 64 of them had factors associated with hypercalcitoninemia besides medullary thyroid cancer. Our study suggests the reference intervals for men who were non, ex-, current smokers, and women (irrespective of smoking status) as <5.7, <7.1, <7.9, and <3.6 pg/mL, respectively. @*Conclusion@#Specific calcitonin reference range should be provided considering for sex and smoking status. Taking account for several factors known to induce hypercalcitoninemia can help interpret the gray zone of moderately elevated calcitonin.

The effect of the response to the coronavirus disease pandemic on treatment outcomes in patients with lymphoma and multiple myeloma

Background/Aims@#Relatively little data are available on how the response to the coronavirus disease 2019 (COVID-19) pandemic has affected treatment outcomes in patients receiving chemotherapy for lymphoma or multiple myeloma. We aimed to determine the effect of COVID-19 countermeasures on treatment outcomes in this patient population. @*Methods@#We retrospectively analyzed data on patients treated for lymphoma or multiple myeloma in two tertiary hospitals in Seoul. Patients were divided into two groups: group 1 included patients who received chemotherapy between September and December 2019 (the control period), and group 2 included patients who received chemotherapy between September and December 2020 (the study period). Countermeasures to COVID-19 were applied to the patients in group 2. The countermeasures implemented included mask wearing and regular handwashing at home and in hospital; COVID-19 risk assessments on all hospital visitors; and pre-emptive COVID-19 screening for all newly hospitalized patients and their resident guardians. @*Results@#No differences in treatment outcomes, including treatment response, incidence and duration of neutropenia or neutropenic fever, delays in chemotherapy, or number of deaths during chemotherapy, were observed between the g roups. None of the patients in group 2 tested positive for COVID-19, and there were no COVID-19-related deaths during the study period. @*Conclusions@#Countermeasures to COVID-19 did not affect treatment outcomes in patients receiving chemotherapy for lymphoma or multiple myeloma. Data on the effect of countermeasures to COVID-19 on treatment outcomes should continue to be analyzed to ensure that treatment outcomes are not adversely affected.

Clinicopathological Characteristics and Disease-Free Survival in Patients with Hürthle Cell Carcinoma: A Multicenter Cohort Study in South Korea

Background@#Hürthle cell carcinoma (HCC), a type of thyroid carcinoma, is rare in South Korea, and few studies have investigated its prognosis. @*Methods@#This long-term multicenter retrospective cohort study evaluated the clinicopathological features and clinical outcomes in patients with HCC who underwent thyroid surgery between 1996 and 2009. @*Results@#The mean age of the 97 patients included in the study was 50.3 years, and 26.8% were male. The mean size of the primary tumor was 3.2±1.8 cm, and three (3.1%) patients had distant metastasis at initial diagnosis. Ultrasonographic findings were available for 73 patients; the number of nodules with low-, intermediate-, and high suspicion was 28 (38.4%), 27 (37.0%), and 18 (24.7%), respectively, based on the Korean-Thyroid Imaging Reporting and Data System. Preoperatively, follicular neoplasm (FN) or suspicion for FN accounted for 65.2% of the cases according to the Bethesda category, and 13% had malignancy or suspicious for malignancy. During a median follow-up of 8.5 years, eight (8.2%) patients had persistent/recurrent disease, and none died of HCC. Older age, gross extrathyroidal extension (ETE), and widely invasive types of tumors were significantly associated with distant metastasis (all P<0.01). Gross ETE (hazard ratio [HR], 27.7; 95% confidence interval [CI], 2.2 to 346.4; P=0.01) and widely invasive classification (HR, 6.5; 95% CI, 1.1 to 39.4; P=0.04) were independent risk factors for poor disease-free survival (DFS). @*Conclusion@#The long-term prognosis of HCC is relatively favorable in South Korea from this study, although this is not a nation-wide data, and gross ETE and widely invasive cancer are significant prognostic factors for DFS. The diagnosis of HCC by ultrasonography and cytopathology remains challenging.

Clinical Characteristics and Prognosis of Coexisting Thyroid Cancer in Patients with Graves’ Disease: A Retrospective Multicenter Study

Background@#The association between Graves’ disease (GD) and co-existing thyroid cancer is still controversial and most of the previously reported data have been based on surgically treated GD patients. This study investigated the clinicopathological findings and prognosis of concomitant thyroid cancer in GD patients in the era of widespread application of ultrasonography. @*Methods@#Data of GD patients who underwent thyroidectomy for thyroid cancer between 2010 and 2019 in three tertiary hospitals in South Korea (Asan Medical Center, Chonnam National University Hwasun Hospital, and Pusan National University Hospital) were collected and analyzed retrospectively. In the subgroup analysis, aggressiveness and clinical outcomes of thyroid cancer were compared nodular GD and non-nodular GD groups according to the presence or absence of the thyroid nodules other than thyroid cancer (index nodules). @*Results@#Of the 15,159 GD patients treated at the hospitals during the study period, 262 (1.7%) underwent thyroidectomy for coexisting thyroid cancer. Eleven patients (4.2%) were diagnosed with occult thyroid cancer and 182 patients (69.5%) had microcarcinomas. No differences in thyroid cancer aggressiveness, ultrasonographic findings, or prognosis were observed between the nodular GD and non-nodular GD groups except the cancer subtype. In the multivariate analysis, only lymph node (LN) metastasis was an independent prognostic factor for recurrent/persistent disease of thyroid cancer arising in GD (P=0.020). @*Conclusion@#The prevalence of concomitant thyroid cancer in GD patients was considerably lower than in previous reports. The clinical outcomes of thyroid cancer in GD patients were also excellent but, more cautious follow-up is necessary for patients with LN metastasis in the same way as for thyroid cancer in non-GD patients.

Clinical Outcomes after Early and Delayed Radioiodine Remnant Ablation in Patients with Low-Risk Papillary Thyroid Carcinoma: Propensity Score Matching Analysis

Background@#The clinical outcomes of delayed radioiodine remnant ablation (RRA) therapy in patients with low-risk papillary thyroid carcinoma (PTC) are unclear. We aimed to evaluate the clinical impact of the interval between total thyroidectomy (TT) and RRA therapy in patients with low-risk PTC. @*Methods@#We included 526 patients who underwent TT and RRA for low-risk PTC with a primary tumor size of >1 cm between 2000 and 2012. Patients were divided into the early (3 months after TT considering other prognostic factors.

Unmet Clinical Needs in the Treatment of Patients with Thyroid Cancer

The increased incidence of thyroid cancer is a worldwide phenomenon; however, the issue of overdiagnosis has been most prominent in South Korea. The age-standardized mortality rate of thyroid cancer in Korea steeply increased from 1985 to 2004 (from 0.17 per 100,000 to 0.85 per 100,000), and then decreased until 2015 to 0.42 per 100,000, suggesting that early detection reduced mortality. However, early detection of thyroid cancer may be cost-ineffective, considering its very high prevalence and indolent course. Therefore, risk stratification and tailored management are vitally important, but many prognostic markers can only be evaluated postoperatively. Discovery of preoperative marker(s), especially for small cancers, is the most important unmet clinical need for thyroid cancer. Herein, we discuss some such factors that we recently discovered. Another unmet clinical need is better treatment of radioiodine-refractory (RAIR) differentiated thyroid cancer (DTC) and undifferentiated cancers. Although sorafenib and lenvatinib are available, better drugs are needed. We found that phosphoglycerate dehydrogenase, a critical enzyme for serine biosynthesis, could be a novel therapeutic target, and that the lymphocyte-to-monocyte ratio is a prognostic marker of survival in patients with anaplastic thyroid carcinoma or RAIR DTC. Deeper insights are needed into tumor-host interactions in thyroid cancer to improve treatment.

Quality of Life in Patients with Papillary Thyroid Microcarcinoma According to Treatment: Total Thyroidectomy with or without Radioactive Iodine Ablation

BACKGROUND: Recently, there has been some controversy regarding the role of radioactive iodine (RAI) ablation in the treatment of low-risk differentiated thyroid carcinoma (DTC), especially papillary thyroid microcarcinoma (PTMC). This study aimed to compare quality of life (QoL) parameters between patients with PTMC who underwent total thyroidectomy (TT) alone and those who underwent TT with RAI ablation.METHODS: In this cross-sectional study, patients with PTMC who underwent TT with/without RAI remnant ablation were prospectively enrolled between June 2016 and October 2017. All patients completed three questionnaires: the 12-item short-form health survey (SF-12), thyroid cancer-specific quality of life (THYCA-QoL) questionnaire, and fear of progression (FoP) questionnaire.RESULTS: The TT and TT with RAI groups comprised 107 and 182 patients, respectively. The TT with RAI group had significantly lower serum thyrotropin (TSH) levels than the TT group. However, after matching for TSH levels between the groups (n=100 in both groups), there were no significant differences in baseline characteristics. According to the SF-12, the score for general health was significantly lower in the TT with RAI group than in the TT group (P=0.047). The THYCA-QoL also showed a significant difference in the “felt chilly” score between groups (P=0.023). No significant differences in FoP scores were observed between the groups.CONCLUSION: Patients with PTMC who underwent TT with RAI ablation experienced more health-related problems than those managed with TT alone. These findings support the idea that RAI ablation should be carefully considered in patients with low-risk DTCs.

Modification of the Tumor-Node-Metastasis Staging System for Differentiated Thyroid Carcinoma by Considering Extra-Thyroidal Extension and Lateral Cervical Lymph Node Metastasis

BACKGROUND: Concerns have arisen about the classification of extra-thyroidal extension (ETE) and lateral cervical lymph node metastasis (N1b) in the 8th edition of the tumor-node-metastasis staging system (TNM-8). This study evaluated the prognostic validity of a modified-TNM staging system, focusing on ETE and N1b, in differentiated thyroid carcinoma (DTC) patients.METHODS: This multicenter retrospective cohort study included 4,878 DTC patients from five tertiary hospitals. In the modified-TNM, T3b in TNM-8 was down-staged to T2, and stage II was subdivided into stages IIA and IIB. Older patients with N1b were reclassified as stage IIB.RESULTS: The modified-TNM resulted in staging migration in 540 patients (11%) classified as stage II according to the TNM-8, with 75 (14%), 381 (71%), and 84 patients (16%) classified as stages I, IIA, and IIB, respectively. The 10-year disease-specific survival (DSS) rates in patients classified as stages I, II, III, and IV by TNM-8 were 99.8%, 95.9%, 81.0%, and 41.6%, respectively. The DSS rates of patients classified as stages I, IIA, IIB, III, and IV according to the modified-TNM were 99.8%, 96.4%, 93.3%, 81.0%, and 41.6%, respectively. DSS curves between stages on TNM-8 (P<0.001) and modified-TNM (P<0.001) differed significantly, but the modified-TNM discriminated better than TNM-8. The proportions of variation explained values of TNM-8 and modified-TNM were 6.3% and 6.5%, respectively.CONCLUSION: Modification of the TNM staging system focusing on ETE and N1b could improve the prediction of DSS in patients with DTC. Further researches are needed to validate the prognostic accuracy of this modified-TNM staging system.

Survival Benefit of Palliative Primary Tumor Resection Based on Tumor Location in Patients with Metastatic Colorectal Cancer: A Single-center Retrospective Study / 대한소화기학회지

Background/Aims@#The molecular underpinnings of colorectal cancer (CRC) vary according to the tumor location. The advantages of a palliative primary tumor resection in patients with metastatic CRC are controversial. This study examined the survival outcomes of a palliative primary tumor resection based on the tumor location in patients with metastatic CRC. @*Methods@#The medical records of 600 patients diagnosed with metastatic CRC between January 2000 and June 2018 were reviewed retrospectively. Patients undergoing surgery for both the primary tumor and metastatic lesions were excluded. The clinical factors affecting the long-term outcomes were evaluated according to the primary tumor location, and the long-term survival was compared between patients with and without a palliative primary tumor resection. The data were analyzed using the Kaplan-Meier estimator and multivariate Cox regression models. @*Results@#The median follow-up duration was 18 months (interquartile range, 10-28). Patients with right-sided CRC had a poor overall- and progression-free survival compared to those with left-sided CRC. In multivariate Cox regression analysis, the palliative primary tumor resection was an independent prognostic factor predicting better overall survival in patients with metastatic CRC, regardless of the primary tumor location. @*Conclusions@#The primary tumor location influences the prognosis, and that a primary tumor resection can improve the overall survival in patients with metastatic CRC, regardless of the primary tumor location.

Vandetanib for the Management of Advanced Medullary Thyroid Cancer: A Real-World Multicenter Experience

Background@#Vandetanib is the most widely used tyrosine kinase inhibitor for the treatment of patients with advanced medullary thyroid cancer (MTC). However, only limited data regarding its use outside clinical trials are available. We aimed to evaluate the efficacy and safety of vandetanib in patients with advanced MTC in routine clinical practice. @*Methods@#In this multicenter retrospective study, 12 patients with locally advanced or metastatic MTC treated with vandetanib at four tertiary hospitals were included. The primary outcome was the objective response rate (ORR) based on the Response Evaluation Criteria in Solid Tumors. The progression-free survival (PFS), overall survival (OS), and toxicities were also evaluated. @*Results@#Eleven patients (92%) had distant metastasis and 10 (83%) had disease progression at enrollment. Partial response was observed in five patients (ORR, 42%) and stable disease lasting ≥24 weeks was reported in an additional five patients (83%). During the median 31.7 months of follow-up, disease progression was seen in five patients (42%); of these, two died due to disease progression. The median PFS was 25.9 months, while the median OS was not reached. All patients experienced adverse events (AEs) which were generally consistent with the known safety profile of vandetanib. Vandetanib was discontinued in two patients due to skin toxicity. @*Conclusion@#Consistent with the phase III trial, this study confirmed the efficacy of vandetanib for advanced MTC in terms of both ORR and PFS in the real-world setting. Vandetanib was well tolerated in the majority of patients, and there were no fatal AEs.