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Purpose@#The KNOG-1101 study showed improved 2-year PFS with temozolomide during and after radiotherapy compared to radiotherapy alone for patients with anaplastic gliomas. This trial investigates the effect of concurrent and adjuvant temozolomide on health-related quality of life (HRQoL). @*Materials and Methods@#In this randomized, open-label, phase II trial, 90 patients with World Health Organization grade III glioma were enrolled across multiple centers in South Korea between March 2012 to February 2015 and followed up through 2017. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) and 20-item EORTC QLQ-Brain Neoplasm (QLQ-BN20) were used to compare HRQoL between patients assigned to concurrent chemoradiotherapy with temozolomide followed by 6 cycles of adjuvant temozolomide (arm A) and radiotherapy (RT) alone (arm B). @*Results@#Of the 90 patients in the study, 84 patients (93.3%) completed the baseline HRQoL questionnaire. Emotional functioning, fatigue, nausea and vomiting, dyspnea, constipation, appetite loss, diarrhea, seizures, itchy skin, drowsiness, hair loss, and bladder control were not affected by the addition of temozolomide. All other items did not differ significantly between arm A and arm B throughout treatment. Global health status particularly stayed consistent at the end of adjuvant temozolomide (p=0.47) and at the end of RT (p=0.33). @*Conclusion@#The addition of concurrent and adjuvant temozolomide did not show negative influence on HRQoL with improvement of progression-free survival for patients with anaplastic gliomas. The absence of systematic and clinically relevant changes in HRQoL suggests that an overall long-term net clinical benefit exists for concurrent and adjuvant temozolomide.
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Objective@#: Here, we evaluated whether cerebrospinal fluid (CSF) profiles and their changes after intraventricular chemotherapy for leptomeningeal carcinomatosis (LMC) could predict the treatment response or be prognostic for patient overall survival (OS) along with clinical factors. @*Methods@#: Paired 1) pretreatment lumbar, 2) pretreatment ventricular, and 3) posttreatment ventricular samples and their CSF profiles were collected retrospectively from 148 LMC patients who received Ommaya reservoir installation and intraventricular chemotherapy. CSF profile changes were assessed by calculating the differences between posttreatment and pretreatment samples from the same ventricular compartment. CSF cell counts were further differentiated into total and other based on clinical laboratory reports. @*Results@#: For the treatment response, a decreased CSF ‘total’ cell count tended to be associated with a ‘controlled’ increase in intracranial pressure (ICP) (p=0.059), but other profile changes were not associated with either the control of increased ICP or the cytology response. Among the pretreatment CSF profiles, lumbar protein level and ventricular cell count were significantly correlated with OS in univariable analysis, but they were not significant in multi-variable analysis. Among CSF profile changes, a decrease in ‘other’ cell count showed worse OS than ‘no change’ or increased groups (p=0.001). The cytological response was significant for OS, but the hazard ratio of partial remission was paradoxically higher than that of ‘no response’. @*Conclusion@#: A decrease in other cell count of CSF after intraventricular chemotherapy was associated with poor OS in LMC patients. We suggest that more specific CSF biomarkers of cancer cell origin are needed.
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Objective@#: Here, we evaluated whether cerebrospinal fluid (CSF) profiles and their changes after intraventricular chemotherapy for leptomeningeal carcinomatosis (LMC) could predict the treatment response or be prognostic for patient overall survival (OS) along with clinical factors. @*Methods@#: Paired 1) pretreatment lumbar, 2) pretreatment ventricular, and 3) posttreatment ventricular samples and their CSF profiles were collected retrospectively from 148 LMC patients who received Ommaya reservoir installation and intraventricular chemotherapy. CSF profile changes were assessed by calculating the differences between posttreatment and pretreatment samples from the same ventricular compartment. CSF cell counts were further differentiated into total and other based on clinical laboratory reports. @*Results@#: For the treatment response, a decreased CSF ‘total’ cell count tended to be associated with a ‘controlled’ increase in intracranial pressure (ICP) (p=0.059), but other profile changes were not associated with either the control of increased ICP or the cytology response. Among the pretreatment CSF profiles, lumbar protein level and ventricular cell count were significantly correlated with OS in univariable analysis, but they were not significant in multi-variable analysis. Among CSF profile changes, a decrease in ‘other’ cell count showed worse OS than ‘no change’ or increased groups (p=0.001). The cytological response was significant for OS, but the hazard ratio of partial remission was paradoxically higher than that of ‘no response’. @*Conclusion@#: A decrease in other cell count of CSF after intraventricular chemotherapy was associated with poor OS in LMC patients. We suggest that more specific CSF biomarkers of cancer cell origin are needed.
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Purpose@#Squamous cell carcinomas (SqCC) of the lung often express high levels of thymidylate synthase (TS), which is associated with primary resistance to pemetrexed. We explored the efficacy of pemetrexed in a selected population of patients with lung SqCC with low TS expression. @*Materials and Methods@#In this single-arm phase II trial, we enrolled 32 previously-treated patients with advanced lung SqCC exhibiting low immunohistochemical staining for TS (i.e., in 10% or less of tumor cells). The primary endpoint was 12-week progression-free survival (PFS) rate. @*Results@#Of 32 patients, eight patients (25%) had an Eastern Cooperative Oncology Group performance status of 2, and seven patients (22%) had previously received three or more lines of chemotherapy. The disease control rate from pemetrexed treatment was 30%, and no objective response was observed. The 12-week PFS rate was 24.5% (95% confidence interval [CI], 13.0 to 46.1). Median PFS was 1.3 months (95% CI, 1.3 to 2.7), and median overall survival was 11.8 months (95% CI, 8.1 to not applicable). Most of adverse events were grade 1 or 2. @*Conclusion@#Pemetrexed demonstrated modest activity as a salvage chemotherapy in patients with advanced lung SqCC with low TS expression, although its toxicity was generally manageable.
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Purpose@#We investigated the efficacy of temozolomide during and after radiotherapy in Korean adultswith anaplastic gliomas without 1p/19q co-deletion. @*Materials and Methods@#This was a randomized, open-label, phase 2 study and notably the first multicenter trial forKorean grade III glioma patients. Eligible patients were aged 18 years or older and hadnewly diagnosed non-co-deleted anaplastic glioma with an Eastern Cooperative OncologyGroup performance status of 0-2. Patients were randomized 1:1 to receive radiotherapyalone (60 Gy in 30 fractions of 2 Gy) (control group, n=44) or to receive radiotherapy withconcurrent temozolomide (75 mg/m2/day) followed by adjuvant temozolomide (150-200mg/m2/day for 5 days during six 28-day cycles) (treatment group, n=40). The primary endpointwas 2-year progression-free survival (PFS). Seventy patients (83.3%) were availablefor the analysis of the isocitrate dehydrogenase 1 gene (IDH1) mutation status. @*Results@#The two-year PFS was 42.2% in the treatment group and 37.2% in the control group. Overallsurvival (OS) did not reach to significant difference between the groups. In multivariableanalysis, age was a significant risk factor for PFS (hazard ratio [HR], 2.08; 95% confidenceinterval [CI], 1.04 to 4.16). The IDH1mutation was the only significant prognostic factor forPFS (HR, 0.28; 95% CI, 0.13 to 0.59) and OS (HR, 0.19; 95% CI, 0.07 to 0.50). Adverseevents over grade 3 were seen in 16 patients (40.0%) in the treatment group and werereversible. @*Conclusion@#Concurrent and adjuvant temozolomide in Korean adults with newly diagnosed nonco-deleted anaplastic gliomas showed improved 2-year PFS. The survival benefit of this regimenneeds further analysis with long-term follow-up at least more than 10 years.
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PURPOSE: The purpose of this study was to develop Korean versions of the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy (NCCN-FACT) Ovarian Symptom Index-18 (NFOSI-18) and FACT/Gynecologic Oncology Group (FACT-GOG) Neurotoxicity 4-item (NTX-4), evaluating their reliability and reproducibility. MATERIALS AND METHODS: In converting NFOSI-18 and NTX-4, the following steps were performed: forward translation, backward translation, expert review, pretest of preliminary format, and finalization of Korean versions (K-NFOSI-18 and K-NTX-4). Patients were enrolled from six institutions where each had completed chemotherapy for ovarian, tubal, or peritoneal cancer at least 1 month earlier. In addition to demographics obtained by questionnaire, all subjects were assessed via K-NFOSI-18, K-NTX-4, and a Korean version of the EuroQoL-5 Dimension. Internal structural validity and reliability were evaluated using item internal consistency, item discriminant validity, and Cronbach's α. To evaluate test-retest reliability, K-NFOSI-18 and K-NTX-4 were readministered after 7-21 days, and intraclass correlation coefficients (ICCs) were calculated. RESULTS: Of the 250 women enrolled during the 3-month recruitment period, 13 withdrew or did not respond, leaving 237 (94.8%) for the analyses. Mean patient age was 54.3±10.8 years. Re-testing was performed in 190 patients (80.2%). The total K-NFOSI-18 and K-NTX-4 scores were 49 (range, 20 to 72) and 9 (range, 0 to 16), respectively, with high reliability (Cronbach's α=0.84 and 0.89, respectively) and reproducibility (ICC=0.77 and 0.84, respectively) achieved in retesting. CONCLUSION: Both NFOSI-18 and NTX-4 were successfully developed in Korean with minimal modification. Each Korean version showed high internal consistency and reproducibility.
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Female , Humans , Demography , Drug Therapy , Fallopian Tubes , Ovarian Neoplasms , Reproducibility of ResultsABSTRACT
PURPOSE: The purpose of this study was to investigate decision patterns to reduce the risks of BRCArelated breast and gynecologic cancers in carriers of BRCA pathogenic variants. We found a change in risk-reducing (RR) management patterns after December 2012, when the National Health Insurance System (NHIS) of Korea began to pay for BRCA testing and riskreducing salpingo-oophorectomy (RRSO) in pathogenic-variant carriers. MATERIALS AND METHODS: The study group consisted of 992 patients, including 705 with breast cancer (BC), 23 with ovarian cancer (OC), 10 with both, and 254 relatives of high-risk patients who underwent BRCA testing at the National Cancer Center of Korea from January 2008 to December 2016.We analyzed patterns of and factors in RR management. RESULTS: Of the 992 patients, 220 (22.2%) were carriers of BRCA pathogenic variants. About 92.3% (203/220) had a family history of BC and/or OC,which significantly differed between BRCA1 and BRCA2 carriers (p < 0.001). All 41 male carriers chose surveillance. Of the 179 female carriers, 59 of the 83 carriers (71.1%) with BC and the 39 of 79 unaffected carriers (49.4%) underwent RR management. None of the carriers affected with OC underwent RR management. Of the management types, RRSO had the highest rate (42.5%) of patient choice. The rate of RR surgery was significantly higher after 2013 than before 2013 (46.3% [74/160] vs. 31.6% [6/19], p < 0.001). CONCLUSION: RRSO was the preferred management for carriers of BRCA pathogenic variants. The most important factors in treatment choice were NHIS reimbursement and/or the severity of illness.
Subject(s)
Female , Humans , Male , Breast , Breast Neoplasms , Korea , National Health Programs , Ovarian Neoplasms , Prophylactic Surgical ProceduresABSTRACT
PURPOSE: The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and the Memorial Sloan Kettering Cancer Center (MSKCC) risk models were developed predominantly with clear cell renal cell carcinoma (RCC). Accordingly, whether these two models could be applied to metastatic non-clear cell RCC (mNCCRCC) as well has not been well-known and was investigated herein. MATERIALS AND METHODS: From the Korean metastatic RCC registry, a total of 156 patients (8.1%) with mNCCRCC among the entire cohort of 1,922 patients were analyzed. Both models were applied to predict first-line progression-free survival (PFS), total PFS, and cancer-specific survival (CSS). RESULTS: The median first-line PFS, total PFS, and CSS were 5, 6, and 24 months, respectively. The IMDC risk model reliably discriminated three risk groups to predict survival: the median first-line PFS, total PFS, and CSS for the favorable, intermediate, and poor risk groups were 9, 5, and, 2 months (p=0.001); 14, 7, and 2 months (p < 0.001); and 41, 21, and 8 months (p < 0.001), all respectively. The MSKCC risk model also reliably differentiated three risk groups: 9, 5, and, 2 months (p=0.005); 10, 7, and 3 months (p=0.002); and 50, 21, and 8 months (p < 0.001), also all respectively. The concordance indices were 0.632 with the IMDC model and 0.643 with the MSKCC model for first-line PFS: 0.748 and 0.655 for CSS. CONCLUSION: The current IMDC and MSKCC risk models reliably predict first-line PFS, total PFS, and CSS in mNCCRCC.
Subject(s)
Humans , Carcinoma, Renal Cell , Cohort Studies , Disease-Free Survival , Prognosis , Retrospective StudiesABSTRACT
BACKGROUND: To evaluate the efficacy of modified ventriculolumbar perfusion (VLP) chemotherapy with methotrexate on leptomeningeal carcinomatosis in terms of symptomatic response and side effects. METHODS: Previous infusion rate of 20 mL/h was reduced to 15 mL/h for the purpose of decreasing constitutional side effects of VLP such as nausea/vomiting, insomnia and confusion. The primary outcome was the response rate of increased intracranial pressure (ICP), and the secondary outcome was the occurrence of side effects compared to previous 20 mL/h trial. This interim analysis to validate the reduced infusion rate is not to affect the original effect of VLP chemotherapy. RESULTS: All forty-seven patients were enrolled including 22 patients with increased ICP. Thirteen patients out of these (59%) got normalized ICP after VLP chemotherapy. Moderate to severe (grade 2–3) confusion was observed in 3 patients (6%) and it was significantly reduced compared to those (23%) in the VLP 20 mL/h (p=0.017). Grade 2–3 nausea/vomiting was also reduced from 64% to 45% but failed to reach statistical significance (p=0.08). Median overall survival (OS) was 5.3 months (95% confidence interval, 3.55–7.05) and patients OS, who received maintenance VLP was significantly prolonged compared to patients who underwent induction VLP only (5.8 vs. 3.4 months, p=0.025). CONCLUSION: VLP of reduced perfusion rate (15 mL/h) showed compatible control rate of increased ICP at this interim analysis. Decreased moderate to severe side effects and prolonged OS in patients received maintenance VLP encourage us to evaluate the effectiveness of this trial further.
Subject(s)
Humans , Drug Therapy , Infusions, Intraventricular , Intracranial Pressure , Meningeal Carcinomatosis , Methotrexate , Perfusion , Sleep Initiation and Maintenance DisordersABSTRACT
PURPOSE: Liver resection is considered the only curative treatment modality for colorectal liver metastasis. The recurrence rate after hepatectomy is >50%. Two or more hepatectomies are applied to treat recurred metastases. We assessed the efficiency and feasibility of repeat hepatectomy and analyzed the prognostic factors after a repeat hepatectomy. METHODS: In total, 248 patients were diagnosed with recurred liver metastasis between January 2003 and May 2016. Second and third hepatectomies were performed in 70 and 7 patients, respectively. The other 171 patients did not undergo a repeat hepatectomy. Clinical features were collected from the medical records. We analyzed survival rates of the repeat hepatectomy group and the nonrepeat hepatectomy group. We also investigated factors affecting overall and disease-free survival of patients who received a repeat hepatectomy using univariate and multivariate analyses. RESULTS: Median overall survival was significantly higher in the repeat hepatectomy group than in the nonrepeat group (83.0 months vs. 25.0 months, P < 0.001). The morbidity and mortality rates of repeat hepatectomy were 9.1% and 0%, respectively. Median overall and disease-free survival of the repeat hepatectomy group were 62.0 and 51.0 months, respectively. The number of recurred tumors was the only significant factor for disease-free survival (P = 0.029). None of the factors affected overall survival. CONCLUSION: Repeat hepatectomy is necessary, effective, and safe for treating recurred colorectal liver metastasis. Repeat hepatectomy can be considered in patients with fewer than three recurred metastatic tumors.
Subject(s)
Humans , Colorectal Neoplasms , Disease-Free Survival , Feasibility Studies , Hepatectomy , Liver , Medical Records , Mortality , Multivariate Analysis , Neoplasm Metastasis , Prognosis , Recurrence , Survival RateABSTRACT
PURPOSE: Patients often complain of change of defecation pattern and it is necessary to quantify their symptoms. To quantify symptoms, use of questionnaire is ideal, so we adopted a simple and easily writable visual analogue scale for irritable bowel syndrome questionnaire (VAS-IBS). The aim of this study was to develop and validate the Korean version of VAS-IBS questionnaire (Korean VAS-IBS) that can adequately reflect the defecation pattern. METHODS: This study translated English VAS-IBS into Korean using the forward-and-back translation method. Korean VAS-IBS was performed on 30 patients, who visited the outpatient clinic and had no possibility of special defecation pattern. Detailed past medical history and Bristol stool chart was added to the questionnaire. The survey was conducted twice, and the median interval between the 2 surveys was 10 days (8–11 days). Cronbach α for internal consistency reliability and intraclass correlation coefficients for test-retest reliability were analyzed. RESULTS: Korean VAS-IBS achieved acceptable homogeneity with a Cronbach α coefficient of 0.66–0.79 showing adequate internal consistency reliability. In addition, intraclass correlation coefficients showed significant test-retest reliability with 0.46–0.80 except for the question assessing the “perception of psychological wellbeing.” CONCLUSION: The Korean VAS-IBS is a valid and reliable questionnaire for the measurement of the symptoms of defecation pattern changes.
Subject(s)
Humans , Ambulatory Care Facilities , Defecation , Irritable Bowel Syndrome , Methods , Reproducibility of Results , Translations , Visual Analog ScaleABSTRACT
PURPOSE: The purpose of this study was to develop a Korean version of the self-reported thyroid-specific quality of life (QoL) questionnaire for thyroid cancer patients (KT-QoL), and to evaluate its reliability and validity. MATERIALS AND METHODS: Two hundred seventy-two patients who underwent thyroidectomy from January to December 2010 were recruited in this study. The original version of the thyroid QoL was translated into Korean and evaluated for its reliability and validity. Using the developed KT-QoL, the postoperative QoL was evaluated until postoperative 1 year. RESULTS: At the preoperative baseline, the item internal consistency (IIC) ranged from −0.19 to 0.76, with low IIC values for items 2, 17, and 27. Item discriminant validity ranged from 86% to 97%. These values were similar at the postoperative periods. The internal consistency reliability (Cronbach's α) was high for all dimensions, ranging from 0.90 to 0.95. The test-retest reliability (intraclass correlation coefficient) was acceptable (0.74-0.82). The external validity examined by the correlation between the item 1j (voice changes) of KT-QoL and the voice handicap index-30 ranged from 0.51 to 0.75. Patients' QoL scores decreased after surgery, which demonstrated the sensitivity of the questionnaire. The QoL scores in patients with lobectomy showed best QoL scores postoperatively and those with receiving radioactive iodine still showed decreased QoL scores along the postoperative periods. CONCLUSION: These results demonstrate that KT-QoL is a valid instrument for evaluating QoL of Korean patients with thyroid cancer.
Subject(s)
Humans , Iodine , Postoperative Period , Quality of Life , Reproducibility of Results , Surveys and Questionnaires , Thyroid Gland , Thyroid Neoplasms , Thyroidectomy , VoiceABSTRACT
PURPOSE: This study assessed the feasibility and compliance of induction chemotherapy with gemcitabine and cisplatin followed by simultaneous integrated boost–intensity modulated radiotherapy (SIB-IMRT) with concurrent gemcitabine in patients with locally advanced unresectable pancreatic cancer. MATERIALS AND METHODS: In this trial, patients received induction chemotherapy consisting of gemcitabine (1,000 mg/m²) and cisplatin (25 mg/m²) on days 1, 8, and 15 of each treatment cycle. Patients were subsequently treated with gemcitabine (300 mg/m²/wk) during SIB-IMRT. The patients received total doses of 55 and 44 Gy in 22 fractions to planning target volume 1 and 2, respectively. As an ancillary study, digital polymerase chain reaction was performed to screen for the seven most common mutations in codons 12 and 13 of the KRAS oncogene of circulating cell free DNA (cfDNA). RESULTS: Forty-four patients were enrolled between 2012 and 2015. Of these, 33 (75%) completed the treatment. The most common toxicities during induction chemotherapy were grades 3 and 4 neutropenia (18.2%), grade 3 nausea (6.8%) and vomiting (6.8%). The most common toxicities during SIB-IMRT were grade 3 neutropenia (24.2%) and grade 3 anemia (12.1%). Ten patients (23%) underwent a curative resection after therapy. Median overall survival was significantly longer in patients who underwent curative resection (16.8 months vs. 11 months, p < 0.01). The median cfDNA concentration was significantly lower after treatment (108.5 ng/mL vs. 18.4 ng/mL, p < 0.001). CONCLUSION: Induction chemotherapy with gemcitabine and cisplatin followed by concurrent SIB-IMRT was well tolerated and active.
Subject(s)
Humans , Anemia , Cisplatin , Codon , Compliance , DNA , Feasibility Studies , Induction Chemotherapy , Nausea , Neutropenia , Oncogenes , Pancreatic Neoplasms , Polymerase Chain Reaction , Radiotherapy , VomitingABSTRACT
OBJECTIVE: The Gynecologic Cancer Lymphedema Questionnaire (GCLQ) was designed to identify gynecologic cancer patients with lower limb lymphedema (LLL). The questionnaire consists of 20 items distributed over 7 symptom clusters. The present study aimed to develop an abridged form of the GCLQ for simpler screening and more effective follow-up of LLL. METHODS: Data that had been collected for the development and validation of the Korean version of the GCLQ (GCLQ-K) were used in this study. Receiver-operating characteristic (ROC) curves were drawn according to the individual items of the GCLQ-K. Based on discrimination ability, the candidate items were selected in each symptom cluster. After combining the items, the best model was identified and named GCLQ-7. The area under the ROC curve (AUC) was compared between the GCLQ-7 and the original GCLQ-K. RESULTS: In total, 11 candidate items were selected from the original GCLQ-K. Among the models made with the candidate items, GCLQ-7, the best model, was constructed with 7 items as follows: 1) limited knee movement, 2) general swelling, 3) redness, 4) firmness/tightness, 5) groin swelling, 6) heaviness, and 7) aching. This model exhibited an AUC of 0.945 (95% confidence interval [CI], 0.900–0.991), which is comparable with that of the original GCLQ-K (AUC, 0.867; 95% CI, 0.779–0.956). The best cutoff value was 2 points, at which the sensitivity and specificity were 97.0% and 76.5%, respectively. CONCLUSION: The newly developed short version model, GCLQ-7, showed acceptable discrimination ability as compared with the original GCLQ-K.
Subject(s)
Female , Humans , Area Under Curve , Discrimination, Psychological , Endometrial Neoplasms , Follow-Up Studies , Genital Neoplasms, Female , Groin , Knee , Lower Extremity , Lymphedema , Mass Screening , Ovarian Neoplasms , ROC Curve , Sensitivity and Specificity , Surveys and Questionnaires , Uterine Cervical NeoplasmsABSTRACT
PURPOSE: The purpose of this study was to evaluate the impact of postmastectomy radiotherapy (PMRT) on loco-regional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival (OS) in pT1-2N1 patients treated with taxane-based chemotherapy. MATERIALS AND METHODS: We retrospectively reviewed the medical data of pathological N1 patients who were treated with modified radical mastectomy and adjuvant taxane-based chemotherapy in 12 hospitals between January 2006 and December 2010. RESULTS: We identified 714 consecutive patients. The median follow-up duration was 69 months (range, 1 to 114 months) and the 5-year LRRFS, DFS, and OS rates were 97%, 94%, and 98%, respectively, in patients who received PMRT (PMRT [+]). The corresponding figures were 96%, 90%, and 96%, respectively, in patients who did not receive PMRT (PMRT [–]). PMRT had no significant impact on survival. Upon multivariable analysis, only the histological grade (HG) was statistically significant as a prognostic factor for LRRFS and DFS. In a subgroup analysis of HG 3 patients, PMRT (+) showed better DFS (p=0.081). CONCLUSION: PMRT had no significant impact on LRRFS, DFS, or OS in pT1-2N1 patients treated with taxane-based chemotherapy. PMRT showed a marginal benefit for DFS in HG 3 patients. Randomized studies are needed to confirm the benefit of PMRT in high risk patients, such as those with HG 3.
Subject(s)
Humans , Breast Neoplasms , Breast , Disease-Free Survival , Drug Therapy , Follow-Up Studies , Mastectomy, Modified Radical , Radiotherapy , Recurrence , Retrospective StudiesABSTRACT
PURPOSE: This phase II study examined whether the addition of simvastatin to afatinib provides a clinical benefit compared with afatinib monotherapy in previously treated patients with nonadenocarcinomatous non-small cell lung cancer (NA-NSCLC). MATERIALS AND METHODS: Patients with advanced NA-NSCLC who progressed after one or two chemotherapy regimens were randomly assigned to a simvastatin (40 mg/day) plus afatinib (40 mg/day) (AS) arm or to an afatinib (A) arm. The primary endpoint was response rate (RR). RESULTS: Sixty-eight patients were enrolled (36 in the AS arm and 32 in the A arm). The RR was 5.7% (95% confidence interval [CI], 0.7 to 19.2) for AS and 9.4% (95% CI, 2.0 to 25.0) for A (p=0.440). In arms AS and A, the median progression-free survival (PFS) was 1.0 versus 3.6 months (p=0.240) and the overall survival was 10.0 months versus 7.0 months (p=0.930), respectively. Skin rash, stomatitis, and diarrhea were the most common adverse events in both arms. More grade 3 or 4 diarrhea was observed in arm A (18.8% vs. 5.6% in arm AS). In all patients, the median PFS for treatment including afatinib was not correlated with the status of epidermal growth factor receptor (EGFR) mutation (p=0.122), EGFR fluorescence in situ hybridization (p=0.944), or EGFR immunohistochemistry (p=0.976). However, skin rash severity was significantly related to the risk of progression for afatinib (hazard ratio for skin rash grade ≥ 2 vs. grade < 2, 0.44; 95% CI, 0.25 to 0.78; p=0.005). CONCLUSION: There were no significant differences in the efficacy between AS and A arms in patients with NA-NSCLC.
Subject(s)
Humans , Arm , Carcinoma, Non-Small-Cell Lung , Carcinoma, Squamous Cell , Diarrhea , Disease-Free Survival , Drug Therapy , Exanthema , Fluorescence , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Immunohistochemistry , In Situ Hybridization , ErbB Receptors , Simvastatin , StomatitisABSTRACT
PURPOSE: Defects in the DNA damage repair process can cause genomic instability and play an important role in cervical carcinogenesis. The purpose of this study was to analyze the association of 29 candidate single nucleotide polymorphisms (SNPs) in genes in the DNA repair pathway, TP53, and TP53BP1 with the risk of cervical cancer. MATERIALS AND METHODS: Twenty-nine SNPs in four genes in the DNA repair pathway (ERCC2, ERCC5, NBS1, and XRCC1), TP53, and TP53BP1 were genotyped for 478 cervical cancer patients and 922 healthy control subjects, and their effects on cervical carcinogenesis were analyzed. RESULTS: The most significant association was found for rs17655 in ERCC5, with an age-adjusted p-value < 0.0001, for which a strong additive effect of the risk allele C was observed (odds ratio, 2.01 for CC to GG). On the other hand, another significant polymorphism rs454421 in ERCC2 showed a dominant effect (odds ratio, 1.68 for GA+AA to GG) with an age-adjusted p-value of 0.0009. The association of these polymorphisms remained significant regardless of the age of onset. The significant result for rs17655 was also consistent for subgroups of patients defined by histology and human papillomavirus (HPV) types. However, for rs454421, the association was observed only in patients with squamous cell carcinoma and non-HPV 18 type. CONCLUSION: The results of this study show a novel association of cervical cancer and the genes involved in the nucleotide excision pathway in the Korean population.
Subject(s)
Humans , Age of Onset , Alleles , Carcinogenesis , Carcinoma, Squamous Cell , DNA Damage , DNA Repair , Genomic Instability , Hand , Polymorphism, Single Nucleotide , Uterine Cervical NeoplasmsABSTRACT
PURPOSE: The study was aimed to determine the correlations of tissue-based biomarker expressions between primary and metastatic specimens of renal cell carcinoma and with several well-known prognostic clinicopathological parameters. MATERIALS AND METHODS: The immunohistochemistry (IHC) was used to determine the expression levels of 9 tissue-based markers calculated in H-score expressed by percentage of expression multiplied by the intensity score (0, 1, 2, and 3 points). Using 17 patients' 38 specimens paired with primary renal lesion and its metastatic lesions collected between 2004 and 2015, Tissue microarray with IHC was performed with BAP1, PBRM1, pS6, PTEN, TGase2, PD-L1, CA9, PSMA, and Ki-67 on formalin-fixed paraffin-embedded sections. Pearson correlation and accuracy test were performed to analyze the correlation between primary and metastatic tissues. RESULTS: The 17 patients' mean age was 56.9 years old, mean tumor size was 7.9 cm, and the male to female ratio was 13:4 (76.5%:23.5%), respectively. Three patients had 2, 3, and 3 metastatic tissues, and the rest of 14 patients had only one metastatic tissue. The H-score (PSMA and Ki67) and intensity score (pS6 and PSMA) showed that some differential significant markers were identified which had statistical correlations of expression levels between primary and metastatic lesions among 9 markers. However, no real correlation of PSMA, Ki67, and pS6 markers were found their expressions of between primary and metastatic tissues because of their skewed expressions. CONCLUSIONS: Tissue markers failed to correlate their expression levels in primary lesions with those of metastatic lesions.
Subject(s)
Female , Humans , Male , Biomarkers , Carcinoma, Renal Cell , Immunohistochemistry , Neoplasm MetastasisABSTRACT
OBJECTIVE: Elevated cell counts and protein levels in cerebrospinal fluid (CSF) result from disease activity in patients with leptomeningeal carcinomatosis (LMC). Previous studies evaluated the use of CSF profiles to monitor a treatment response or predict prognosis. CSF profiles vary, however, according to the sampling site and the patient's systemic condition. We compared lumbar and ventricular CSF profiles collected before intraventricular chemotherapy for LMC and evaluated the association of these profiles with patients' systemic factors and LMC disease activity. METHODS: CSF profiles were retrospectively collected from 228 patients who underwent Ommaya reservoir insertion for intraventricular chemotherapy after a diagnosis of LMC. Lumbar samples taken via lumbar puncture were used for the diagnosis, and ventricular samples were obtained later at the time of Ommaya reservoir insertion. LMC disease activity was defined as the presence of LMC-related symptoms such as increased intracranial pressure, hydrocephalus, cranial neuropathy, and cauda equina syndrome. RESULTS: Cell counts (median : 8 vs. 1 cells/mL) and protein levels (median : 68 vs. 17 mg/dL) significantly higher in lumbar CSF than in ventricular CSF (p<0.001). Among the evaluated systemic factors, concomitant brain metastasis and previous radiation were significantly correlated with higher protein levels in the lumbar CSF (p=0.01 and <0.001, respectively). Among the LMC disease activity, patients presenting with hydrocephalus or cauda equina syndrome showed higher lumbar CSF protein level compared with that in patients without those symptoms (p=0.049 and p<0.001, respectively). The lumbar CSF cell count was significantly lower in patients with cranial neuropathy (p=0.046). The ventricular CSF cell counts and protein levels showed no correlation with LMC symptoms. Carcinoembryonic antigen (CEA), which was measured from ventricular CSF after the diagnosis in 109 patients, showed a significant association with the presence of hydrocephalus (p=0.01). CONCLUSION: The protein level in lumbar CSF indicated the localized disease activity of hydrocephalus and cauda equina syndrome. In the ventricular CSF, only the CEA level reflected the presence of hydrocephalus. We suggest using more specific biomarkers for the evaluation of ventricular CSF to monitor disease activity and treatment response.
Subject(s)
Humans , Biomarkers , Brain , Carcinoembryonic Antigen , Cell Count , Cerebrospinal Fluid , Cranial Nerve Diseases , Diagnosis , Drug Therapy , Hydrocephalus , Intracranial Pressure , Meningeal Carcinomatosis , Neoplasm Metastasis , Polyradiculopathy , Prognosis , Retrospective Studies , Spinal PunctureABSTRACT
PURPOSE: The purpose of this study is to compare quality of life (QoL) and sexual functioning between sexually active cervical cancer survivors and healthy women. MATERIALS AND METHODS: In this cross-sectional study, propensity-score-matched cervical cancer survivors (n=104) and healthy women (n=104) were compared. All women had engaged in sexual activity within the previous 3 months, and cervical cancer survivors showed no evidence of disease after primary treatment. QoL and sexual functioning were assessed using three questionnaires; the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), Cervical Cancer Module (EORTC QLQ-CX24), and the Female Sexual Function Index (FSFI). RESULTS: Significantly higher scores for lymphedema were observed in the cervical cancer survivors group compared with the healthy women group (mean, 20.2 vs. 12.2; p < 0.05). Sexuality, both in terms of sexual activity, sexual enjoyment, and sexual worry (EORTC QLQ-CX24), and in terms of desire, arousal, lubrication, orgasm, satisfaction, and pain (FSFI) were similar between the groups. When the scale of sexual/vaginal functioning in EORTC QLQ-CX24 was divided into individual questions, cervical cancer survivors reported shorter vaginal length than the control group, but without statistical significance (mean, 80.6 vs. 85.4; p=0.077). CONCLUSION: Compared with healthy women, sexuality was not impaired in cervical cancer survivors who showed no evidence of disease after primary treatment and engaging in sexual activity. Further prospective cohort studies are warranted to confirm this finding.