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Background@#Research regarding cervical metastasis from an unknown primary tumor (CUP) according to human papillomavirus (HPV) and Epstein-Barr virus (EBV) status in Korea has been sporadic and small-scale. This study aims to analyze and understand the characteristics of CUP in Korea according to viral and p16 and p53 status through a multicenter study. @*Methods@#Ninety-five cases of CUP retrieved from six hospitals in Korea between January 2006 and December 2016 were subjected to high-risk HPV detection (DNA in situ hybridization [ISH] or real-time polymerase chain reaction), EBV detection (ISH), and immunohistochemistry for p16 and p53. @*Results@#CUP was HPV-related in 37 cases (38.9%), EBV-related in five cases (5.3%), and unrelated to HPV or EBV in 46 cases (48.4%). HPV-related CUP cases had the best overall survival (OS) (p = .004). According to the multivariate analysis, virus-unrelated disease (p = .023) and longer smoking duration (p < .005) were prognostic factors for poor OS. Cystic change (p = .016) and basaloid pattern (p < .001) were more frequent in HPV-related cases, and lymphoepithelial lesion was frequent in EBV-related cases (p = .010). There was no significant association between viral status and p53 positivity (p = .341), smoking status (p = .728), or smoking duration (p = .187). Korean data differ from Western data in the absence of an association among HPV, p53 positivity, and smoking history. @*Conclusions@#Virus-unrelated CUP in Korea had the highest frequency among all CUP cases. HPV-related CUP is similar to HPV-mediated oropharyngeal cancer and EBVrelated CUP is similar to nasopharyngeal cancer in terms of characteristics, respectively.
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Background@#The metastatic brain tumor is the most common brain tumor. The aim of this study was to demonstrate the clinicopathological and molecular pathologic features of brain metastases (BM). @*Methods@#A total of 269 patients were diagnosed with BM through surgical resection at Seoul St. Mary’s Hospital from January 2010 to March 2020. We reviewed the clinicopathological features and molecular status of primary and metastatic brain tissues using immunohistochemistry and molecular pathology results. @*Results@#Among 269 patients, 139 males and 130 females were included. The median age of primary tumor was 58 years (range, 13 to 87 years) and 86 patients (32.0%) had BM at initial presentation. Median BM free interval was 28.0 months (range, 1 to 286 months). The most frequent primary site was lung 46.5% (125/269), and followed by breast 15.6% (42/269), colorectum 10.0% (27/269). Epidermal growth factor receptor (EGFR) mutation was found in 50.8% (32/63) and 58.0% (40/69) of lung primary and BM, respectively. In both breast primary and breast cancer with BM, luminal B was the most frequent subtype at 37.9% (11/29) and 42.9% (18/42), respectively, followed by human epidermal growth factor receptor 2 with 31.0% (9/29) and 33.3% (14/42). Triple-negative was 20.7% (6/29) and 16.7% (7/42), and luminal A was 10.3% (3/29) and 7.1% (3/42) of breast primary and BM, respectively. In colorectal primary and colorectal cancer with BM, KRAS mutation was found in 76.9% (10/13) and 66.7% (2/3), respectively. @*Conclusions@#We report the clinicopathological and molecular pathologic features of BM that can provide useful information for understanding the pathogenesis of metastasis and for clinical trials based on the tumor’s molecular pathology.
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Background@#There have been no guidelines for the management of adult patients with diffuse midline glioma (DMG), H3K27M-mutant in Korea since the 2016 revised WHO classification newly defined this disease entity. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for DMG since 2019. @*Methods@#The Working Group was composed of 27 multidisciplinary medical experts in Korea.References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. As ‘diffuse midline glioma’ was recently defined, and there was no international guideline, trials and guidelines of ‘diffuse intrinsic pontine glioma’ or ‘brain stem glioma’ were thoroughly reviewed first. @*Results@#The core contents are as follows. The DMG can be diagnosed when all of the following three criteria are satisfied: the presence of the H3K27M mutation, midline location, and infiltrating feature. Without identification of H3K27M mutation by diagnostic biopsy, DMG cannot be diagnosed. For the primary treatment, maximal safe resection should be considered for tumors when feasible. Radiotherapy is the primary option for tumors in case the total resection is not possible. A total dose of 54 Gy to 60 Gy with conventional fractionation prescribed at 1-2 cm plus gross tumor volume is recommended. Although no chemotherapy has proven to be effective in DMG, concurrent chemoradiotherapy (± maintenance chemotherapy) with temozolomide following WHO grade IV glioblastoma’s protocol is recommended. @*Conclusion@#The detection of H3K27M mutation is the most important diagnostic criteria for DMG. Combination of surgery (if amenable to surgery), radiotherapy, and chemotherapy based on comprehensive multidisciplinary discussion can be considered as the treatment options for DMG.
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Background@#To date, there has been no practical guidelines for the prescription of antiepileptic drugs (AEDs) in brain tumor patients in Korea. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for AED usage in brain tumors since 2019. @*Methods@#The Working Group was composed of 27 multidisciplinary medical experts in Korea.References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of the keywords. @*Results@#The core contents are as follows. Prophylactic AED administration is not recommended in newly diagnosed brain tumor patients without previous seizure history. When AEDs are administered during peri/postoperative period, it may be tapered off according to the following recommendations. In seizure-naïve patients with no postoperative seizure, it is recommended to stop or reduce AED 1 week after surgery. In seizure-naïve patients with one early postoperative seizure (<1 week after surgery), it is advisable to maintain AED for at least 3 months before tapering. In seizure-naïve patients with ≥2 postoperative seizures or in patients with preoperative seizure history, it is recommended to maintain AEDs for more than 1 year. The possibility of drug interactions should be considered when selecting AEDs in brain tumor patients. Driving can be allowed in brain tumor patients when proven to be seizure-free for more than 1 year. @*Conclusion@#The KSNO suggests prescribing AEDs in patients with brain tumor based on the current guideline. This guideline will contribute to spreading evidence-based prescription of AEDs in brain tumor patients in Korea.
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Background@#There have been no guidelines for the management of adult patients with diffuse midline glioma (DMG), H3K27M-mutant in Korea since the 2016 revised WHO classification newly defined this disease entity. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for DMG since 2019. @*Methods@#The Working Group was composed of 27 multidisciplinary medical experts in Korea.References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. As ‘diffuse midline glioma’ was recently defined, and there was no international guideline, trials and guidelines of ‘diffuse intrinsic pontine glioma’ or ‘brain stem glioma’ were thoroughly reviewed first. @*Results@#The core contents are as follows. The DMG can be diagnosed when all of the following three criteria are satisfied: the presence of the H3K27M mutation, midline location, and infiltrating feature. Without identification of H3K27M mutation by diagnostic biopsy, DMG cannot be diagnosed. For the primary treatment, maximal safe resection should be considered for tumors when feasible. Radiotherapy is the primary option for tumors in case the total resection is not possible. A total dose of 54 Gy to 60 Gy with conventional fractionation prescribed at 1-2 cm plus gross tumor volume is recommended. Although no chemotherapy has proven to be effective in DMG, concurrent chemoradiotherapy (± maintenance chemotherapy) with temozolomide following WHO grade IV glioblastoma’s protocol is recommended. @*Conclusion@#The detection of H3K27M mutation is the most important diagnostic criteria for DMG. Combination of surgery (if amenable to surgery), radiotherapy, and chemotherapy based on comprehensive multidisciplinary discussion can be considered as the treatment options for DMG.
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Background@#To date, there has been no practical guidelines for the prescription of antiepileptic drugs (AEDs) in brain tumor patients in Korea. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for AED usage in brain tumors since 2019. @*Methods@#The Working Group was composed of 27 multidisciplinary medical experts in Korea.References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of the keywords. @*Results@#The core contents are as follows. Prophylactic AED administration is not recommended in newly diagnosed brain tumor patients without previous seizure history. When AEDs are administered during peri/postoperative period, it may be tapered off according to the following recommendations. In seizure-naïve patients with no postoperative seizure, it is recommended to stop or reduce AED 1 week after surgery. In seizure-naïve patients with one early postoperative seizure (<1 week after surgery), it is advisable to maintain AED for at least 3 months before tapering. In seizure-naïve patients with ≥2 postoperative seizures or in patients with preoperative seizure history, it is recommended to maintain AEDs for more than 1 year. The possibility of drug interactions should be considered when selecting AEDs in brain tumor patients. Driving can be allowed in brain tumor patients when proven to be seizure-free for more than 1 year. @*Conclusion@#The KSNO suggests prescribing AEDs in patients with brain tumor based on the current guideline. This guideline will contribute to spreading evidence-based prescription of AEDs in brain tumor patients in Korea.
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Background@#High-risk (HR) human papillomavirus (HPV) is found in a subset of head and neck (HN) squamous cell carcinomas (SCCs). For oropharyngeal SCCs, HR HPV positivity is known to be associated with good prognosis, and a separate staging system for HPV-associated carcinomas using p16 immunohistochemistry (IHC) as a surrogate test has been adopted in the 8th American Joint Committee on Cancer staging system. We examined the HR HPV status and the genotype distribution in five HN subsites. @*Methods@#Formalin-fixed paraffin-embedded tissue sections were used for p16 IHC and DNA extraction. HPV DNA detection and genotyping were done employing either a DNA chip-based or real-time polymerase chain reaction–based method. @*Results@#During 2011–2019, a total of 466 SCCs were tested for HPV DNA with 34.1% positivity for HR HPV. Among HN subsites, the oropharynx showed the highest HR HPV prevalence (149/205, 75.1%), followed by the sinonasal tract (3/14, 21.4%), larynx (5/43, 11.6%), hypopharynx (1/38, 2.6%), and oral cavity (1/166, 0.6%). The most common HPV genotype was HPV16 (84.3%) followed by HPV35 (6.9%) and HPV33 (4.4%). Compared with HR HPV status, the sensitivity and specificity of p16 IHC were 98.6% and 94.3% for the oropharynx, and 99.2% and 93.8% for the tonsil, respectively. @*Conclusions@#Using a Korean dataset, we confirmed that HR HPV is most frequently detected in oropharyngeal SCCs. p16 positivity showed a good concordance with HR HPV DNA for oropharyngeal and especially tonsillar carcinomas. The use of p16 IHC may further be extended to predict HR HPV positivity in sinonasal tract SCCs.
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Meningioma is the most common primary intracranial tumor in adults. The grading of meningioma is based on World Health Organization criteria, which rely on histopathological features alone. This grading system is unable to conclusively predict the clinical behavior of these tumors (i.e., recurrence or prognosis in benign or atypical grades). Advances in molecular techniques over the last decade that include genomic and epigenomic data associated with meningiomas have been used to identify genetic biomarkers that can predict tumor behavior. This review summarizes the molecular characteristics of meningioma using genetic and epigenetic biomarkers. Molecular alterations that can predict meningioma behavior may be integrated into the upcoming World Health Organization grading system.
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Background@#: The Guideline Working Group of the Korean Society for Neuro-Oncology (KSNO)conducted a nationwide questionnaire survey for diverse queries faced in the treatment of brain tumors.As part I of the survey, the aim of this study is to evaluate national patterns of clinical practiceabout antiepileptic drug (AED) and steroid usage for management of brain tumors. @*Methods@#: A web-based survey was sent to all members of the KSNO by email. The survey included9 questions of AED usage and 5 questions of steroid usage for brain tumor patients. All questionswere developed by consensus of the Guideline Working Group. @*Results@#: The overall response rate was 12.8% (54/423). Regarding AED usage, the majority ofrespondents (95.2%) routinely prescribed prophylactic AEDs for patients with seizure at the peri/postoperativeperiod. However, as many as 72.8% of respondents prescribed AED routinely for seizure-naïvepatients, and others prescribed AED as the case may be. The duration of AED prophylaxis showedwide variance according to the epilepsy status and the location of tumor. Levetiracetam (82.9%) wasthe most preferred AED for epilepsy prophylaxis. Regarding steroid usage, 90.5% of respondents usesteroids in perioperative period, including 34.2% of them as a routine manner. Presence of peritumoraledema (90.9%) was considered as the most important factor determining steroid usage followed bydegree of clinical symptoms (60.6%). More than half of respondents (51.2%) replied to discontinue thesteroids within a week after surgery if there are no specific medical conditions, while 7.3% preferredslow tapering up to a month after surgery. @*Conclusion@#: The survey demonstrated the prevailing practice patterns on AED and steroid usagein neuro-oncologic field among members of the KSNO. This information provides a point of referencefor establishing a practical guideline in the management of brain tumor patients.
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Background@#: The Guideline Working Group of the Korean Society for Neuro-Oncology (KSNO)conducted a nationwide questionnaire survey for diverse queries faced in the treatment of brain tumors.As part II of the survey, the aim of this study is to evaluate the national patterns of clinical practicefor patients with diffuse midline glioma and meningioma. @*Methods@#: A web-based survey was sent to all members of the KSNO by email. The survey included4 questions of diffuse midline glioma and 6 questions of meningioma (including 2 case scenarios).All questions were developed by consensus of the Guideline Working Group. @*Results@#: In the survey about diffuse midline glioma, 76% respondents performed histologicconfirmation to identify H3K27M mutation on immunohistochemical staining or sequencing methods.For treatment of diffuse midline glioma, respondents preferred concurrent chemoradiotherapy withtemozolomide (TMZ) and adjuvant TMZ (63.8%) than radiotherapy alone (34.0%). In the surveyabout meningioma, respondents prefer wait-and-see policy for the asymptomatic small meningiomawithout peritumoral edema. However, a greater number of respondents had chosen surgical resectionas the first choice for all large size meningiomas without exception, and small size meningiomaswith either peritumoral edema or eloquent location. There was no single opinion with major consensuson long-term follow-up plans for asymptomatic meningioma with observation policy. As many as68.1% of respondents answered that they would not add any adjuvant therapies for World Health Organizationgrade II meningiomas if the tumor was totally resected including dura. @*Conclusion@#: The survey demonstrates the prevailing clinical practice patterns for patients with diffusemidline glioma and meningioma among members of the KSNO. This information provides a pointof reference for establishing a practical guideline in the management of diffuse midline glioma andmeningioma.
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Background@#: The Guideline Working Group of the Korean Society for Neuro-Oncology (KSNO)conducted the nationwide questionnaire survey for diverse queries facing to treat patients with braintumor. As part III of the survey, the aim of this study is to evaluate the national patterns of clinical practicefor patients with brain metastasis and primary central nervous system lymphoma (PCNSL). @*Methods@#: A web-based survey was sent to all members of the KSNO by email. The survey included7 questions of brain metastasis and 5 questions of PCNSL, focused on the management strategiesin specific situations. All questions were developed by consensus of the Guideline WorkingGroup. @*Results@#" In the survey about brain metastasis, respondents preferred surgical resection withadjuvant treatment for patients with a surgically accessible single brain metastatic lesion less than 3cm in size without extracranial systemic lesions. However, most respondents considered radiosurgeryfor surgically inaccessible lesions. As the preferred treatment of multiple brain metastases according tothe number of brain lesions, respondents tended to choose radiotherapy with increasing number of lesions.Radiosurgery was mostly chosen for the brain metastases of less than or equal to 4. In the surveyabout PCNSL, a half of respondents choose high-dose methotrexate-based polychemotherapy asthe first-line induction therapy for PCNSL. The consolidation and salvage therapy showed a little variationamong respondents. For PCNSL patients with cerebrospinal fluid dissemination, intrathecal chemotherapywas most preferred. @*Conclusion@#: The survey demonstrates the prevailing clinical practice patterns for patients withbrain metastasis and PCNSL among members of the KSNO. This information provides a point of referencefor establishing a practical guideline in the management of brain metastasis and PCNSL.
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BACKGROUND/AIMS: This study investigated the clinical and pathological features of immunoglobulin G4 (IgG4)-related ophthalmic disease. To clarify the features, we compared IgG4-related ophthalmic disease and orbital inflammatory pseudotumor. METHODS: We retrospectively reviewed the medical records of 103 patients who were initially diagnosed with orbital inflammatory pseudotumor, and identified 16 cases in which the diagnosis was based on surgical biopsy and for which data in medical records were sufficient for analysis. Immunohistochemical staining of pathological specimens for IgG and IgG4 was performed. Finally, six of IgG4-related ophthalmic disease patient and 10 of orbital inf lammatory pseudotumor patient were analyzed. RESULTS: The IgG4-related ophthalmic disease group had more IgG4-positive plasma cells and a higher IgG4/IgG plasma cell ratio than the orbital inflammatory pseudotumor group. Collagenous fibrosis and lacrimal gland involvement were significantly more frequent in the IgG4-related ophthalmic disease group. Dense lymphocyte infiltration, obliterative phlebitis, and bilateral lesions were more frequent in IgG4-related ophthalmic disease, but the differences were not significant. The recurrence-free period was shorter in the IgG4-related ophthalmic disease group (p = 0.035). CONCLUSIONS: The location of the lesion (lacrimal gland), count and ratio of IgG4-positive plasma cells, and collagenous fibrosis aid the diagnosis of IgG4-related ophthalmic disease in patients with idiopathic orbital mass-like lesions. In addition, maintenance therapy should be considered in patients with IgG4-related ophthalmic disease to prevent recurrence.
Subject(s)
Humans , Biopsy , Collagen , Diagnosis , Fibrosis , Immunoglobulin G , Immunoglobulins , Lacrimal Apparatus , Lymphocytes , Medical Records , Orbit , Orbital Pseudotumor , Phlebitis , Plasma Cells , Recurrence , Retrospective StudiesABSTRACT
BACKGROUND: There has been no practical guidelines for the management of patients with central nervous system (CNS) tumors in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, started to prepare guidelines for CNS tumors from February 2018. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. RESULTS: First, the maximal safe resection if feasible is recommended. After the diagnosis of a glioblastoma with neurosurgical intervention, patients aged ≤70 years with good performance should be treated by concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide chemotherapy (Stupp's protocol) or standard brain radiotherapy alone. However, those with poor performance should be treated by hypofractionated brain radiotherapy (preferred)±concurrent or adjuvant temozolomide, temozolomide alone (Level III), or supportive treatment. Alternatively, patients aged >70 years with good performance should be treated by hypofractionated brain radiotherapy+concurrent and adjuvant temozolomide or Stupp's protocol or hypofractionated brain radiotherapy alone, while those with poor performance should be treated by hypofractionated brain radiotherapy alone or temozolomide chemotherapy if the patient has methylated MGMT gene promoter (Level III), or supportive treatment. CONCLUSION: The KSNO's guideline recommends that glioblastomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to the individual comprehensive condition of the patient.
Subject(s)
Humans , Brain , Central Nervous System , Chemoradiotherapy , Diagnosis , Drug Therapy , Glioblastoma , Korea , RadiotherapyABSTRACT
BACKGROUND: There was no practical guideline for the management of patients with central nervous system tumor in Korea in the past. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, developed the guideline for glioblastoma successfully and published it in Brain Tumor Research and Treatment, the official journal of KSNO, in April 2019. Recently, the KSNO guideline for World Health Organization (WHO) grade III cerebral glioma in adults has been established. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searches in PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords. Scope of the disease was confined to cerebral anaplastic astrocytoma and oligodendroglioma in adults. RESULTS: Whenever radiological feature suggests high grade glioma, maximal safe resection if feasible is globally recommended. After molecular and histological examinations, patients with anaplastic astrocytoma, isocitrate dehydrogenase (IDH)-mutant should be primary treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy whereas those with anaplastic astrocytoma, NOS, and anaplastic astrocytoma, IDH-wildtype should be treated following the protocol for glioblastomas. In terms of anaplastic oligodendroglioma, IDH-mutant and 1p19q-codeletion, and anaplastic oligodendroglioma, NOS should be primary treated by standard brain radiotherapy and neoadjuvant or adjuvant PCV (procarbazine, lomustine, and vincristine) combination chemotherapy. CONCLUSION: The KSNO's guideline recommends that WHO grade III cerebral glioma of adults should be treated by maximal safe resection if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors.
Subject(s)
Adult , Humans , Astrocytoma , Brain , Brain Neoplasms , Central Nervous System , Drug Therapy , Drug Therapy, Combination , Glioblastoma , Glioma , Isocitrate Dehydrogenase , Korea , Lomustine , Oligodendroglioma , Radiotherapy , World Health OrganizationABSTRACT
BACKGROUND: There was no practical guideline for the management of patients with central nervous system tumor in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has developed the guideline for glioblastoma. Subsequently, the KSNO guideline for World Health Organization (WHO) grade II cerebral glioma in adults is established. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searching PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords regarding diffuse astrocytoma and oligodendroglioma of brain in adults. RESULTS: Whenever radiological feature suggests lower grade glioma, the maximal safe resection if feasible is recommended globally. After molecular and histological examinations, patients with diffuse astrocytoma, isocitrate dehydrogenase (IDH)-wildtype without molecular feature of glioblastoma should be primarily treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy (Level III) while those with molecular feature of glioblastoma should be treated following the protocol for glioblastomas. In terms of patients with diffuse astrocytoma, IDH-mutant and oligodendroglioma (IDH-mutant and 1p19q codeletion), standard brain radiotherapy and adjuvant PCV (procarbazine+lomustine+vincristine) combination chemotherapy should be considered primarily for the high-risk group while observation with regular follow up should be considered for the low-risk group. CONCLUSION: The KSNO's guideline recommends that WHO grade II gliomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors and clinical characteristics of patients.
Subject(s)
Adult , Humans , Astrocytoma , Brain , Central Nervous System , Drug Therapy , Drug Therapy, Combination , Follow-Up Studies , Glioblastoma , Glioma , Isocitrate Dehydrogenase , Korea , Oligodendroglioma , Radiotherapy , World Health OrganizationABSTRACT
PURPOSE: Trastuzumab is an effective treatment for human epidermal growth factor receptor 2 (HER2)-amplified breast cancers. We sought to develop a simple protocol for HER2 image analysis of breast cancer specimens. MATERIALS AND METHODS: In a preliminary test, we found that at least 1000 tumor cells need to be examined in the most strongly stained areas. Next, we evaluated the clinical usefulness of this established protocol of image analysis in 555 breast cancer patients. Results of the HER2 immunohistochemical (IHC) staining were compared between manual scoring and image analysis. RESULTS: The HER2 IHC results obtained by the image analysis method correlated well with those obtained by the manual scoring method (Cohen's kappa=0.830). Using the HER2 silver in situ hybridization (SISH) results as a gold standard, sensitivity values were 72.1% for manual scoring and 74.0% for image analysis; specificity values were 96.2% for manual scoring and 94.7% for image analysis; and accuracy values were 91.7% for manual scoring and 90.8% for image analysis. McNemar's test was applied to the results, and there were no statistically significant differences in sensitivity and specificity between the positive (p=0.688) and negative (p=0.118) SISH groups. CONCLUSION: HER2 image analysis results were similar to those obtained via the manual scoring method, indicating that the use of image analysis can reduce assessment time and effort. We suggest that image analysis-based evaluation of 1000 tumor cells in the most strongly IHC-stained area, regardless of stroma content, is sufficient for determining HER2 expression levels in breast cancer specimens.
Subject(s)
Humans , Breast Neoplasms , Breast , Immunohistochemistry , In Situ Hybridization , Methods , ErbB Receptors , Research Design , Sensitivity and Specificity , Silver , TrastuzumabABSTRACT
BACKGROUND: While procarbazine, CCNU (lomustine), and vincristine (PCV) has been an alternative chemotherapy option for malignant gliomas, it is worth investigating whether the combination of only procarbazine and CCNU is comparable because vincristine adds toxicity with uncertain benefit. The purpose of this study was to evaluate the feasibility of procarbazine and CCNU chemotherapy for recurrent glioblastoma multiforme (GBM) with O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation. METHODS: Eight patients with recurrent GBM following concurrent chemoradiotherapy and temozolomide (TMZ) adjuvant therapy were enrolled in this trial; they received no other chemotherapeutic agents or target therapy. They received CCNU (75 mg/m²) on day 1 and procarbazine (60 mg/m²) through days 11 and 24 every 4 weeks. The median cycle of CCNU and procarbazine was 3.5 (range: 2–6). RESULTS: One patient achieved stable disease. The median progression-free survival (PFS) with procarbazine and CCNU chemotherapy was eight weeks (range: 5–73), and the PFS rates were 25% and 12.5% at 16 and 30 weeks, respectively. The median overall survival (OS) from the initial diagnosis to death was 40 months, and the median OS from the administration of procarbazine and CCNU chemotherapy to death was 9.7 months (95% confidence interval: 6.7–12.7). Serious adverse events were found at six visits, and two cases were considered to be grade 3 toxicities. CONCLUSION: The efficacy of procarbazine and CCNU chemotherapy is not satisfactory. This study suggests the need to develop other treatment strategies for recurrent and TMZ-refractory GBM. Trial registry at ClinicalTrials.gov, NCT017337346.
Subject(s)
Humans , Chemoradiotherapy , Diagnosis , Disease-Free Survival , Drug Therapy , Glioblastoma , Glioma , Lomustine , Methylation , Procarbazine , VincristineABSTRACT
No abstract available.
Subject(s)
Humans , Adenoids , Carcinoma, Adenoid Cystic , Palate, HardABSTRACT
BACKGROUND: Mutations in the KRAS gene have been identified in approximately 50% of colorectal cancers (CRCs). KRAS mutations are well established biomarkers in anti–epidermal growth factor receptor therapy. Therefore, assessment of KRAS mutations is needed in CRC patients to ensure appropriate treatment. METHODS: We compared the analytical performance of the cobas test to Sanger sequencing in 264 CRC cases. In addition, discordant specimens were evaluated by 454 pyrosequencing. RESULTS: KRAS mutations for codons 12/13 were detected in 43.2% of cases (114/264) by Sanger sequencing. Of 257 evaluable specimens for comparison, KRAS mutations were detected in 112 cases (43.6%) by Sanger sequencing and 118 cases (45.9%) by the cobas test. Concordance between the cobas test and Sanger sequencing for each lot was 93.8% positive percent agreement (PPA) and 91.0% negative percent agreement (NPA) for codons 12/13. Results from the cobas test and Sanger sequencing were discordant for 20 cases (7.8%). Twenty discrepant cases were subsequently subjected to 454 pyrosequencing. After comprehensive analysis of the results from combined Sanger sequencing–454 pyrosequencing and the cobas test, PPA was 97.5% and NPA was 100%. CONCLUSIONS: The cobas test is an accurate and sensitive test for detecting KRAS-activating mutations and has analytical power equivalent to Sanger sequencing. Prescreening using the cobas test with subsequent application of Sanger sequencing is the best strategy for routine detection of KRAS mutations in CRC.
Subject(s)
Humans , Biomarkers , Codon , Colorectal NeoplasmsABSTRACT
BACKGROUND: Programmed death ligand 1 (PD-L1) in tumor cells is known to promote immune escape of cancer by interacting with programmed cell death 1 (PD-1) in tumor infiltrating immune cells. Immunotherapy targeting these molecules is emerging as a new strategy for the treatment of glioblastoma (GBM). Understanding the relationship between the PD-L1/PD-1 axis and prognosis in GBM patients may be helpful to predict the effects of immunotherapy. METHODS: PD-L1 expression and PD-1–positive tumor infiltrating mononuclear cell (PD-1+tumor infiltrating mononuclear cell [TIMC]) density were evaluated using tissue microarray containing 54 GBM cases by immunohistochemical analysis; the associations with patient clinical outcomes were evaluated. RESULTS: PD-L1 expression and high PD-1+TIMC density were observed in 31.5% and 50% of GBM cases, respectively. High expression of PD-L1 in tumor cells was an independent and significant predictive factor for worse overall survival (OS; hazard ratio, 4.958; p = .007) but was not a significant factor in disease-free survival (DFS). PD-1+TIMC density was not correlated with OS or DFS. When patients were classified based on PD-1 expression and PD-1+TIMC density, patients with PD-L1+/PD-1+TIMC low status had the shortest OS (13 months, p = .009) and DFS (7 months, p = .053). CONCLUSIONS: PD-L1 expression in GBM was an independent prognostic factor for poor OS. In addition, combined status of PD-L1 expression and PD-1+TIMC density also predicted patient outcomes, suggesting that the therapeutic role of the PD-1/PD-L1 axis should be considered in the context of GBM immunity.