AIM: To assess the efficacy and safety of weekly docetaxel plus a fixed-dose rate (FDR) of gemcitabine in metastatic esophageal squamous cell carcinoma (SCC).
METHODS: A multi-center, open-label, prospective phase II study was designed. Thirty-three esophageal SCC patients with documented progression after fluoropyrimidine/platinum-based first-line chemotherapy were enrolled and treated with docetaxel 35 mg/m2 and gemcitabine 1000 mg/m2 iv at a FDR (10 mg/m2 per minute) on days 1 and 8. Treatment was repeated every twenty-one days until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was response rate (RR), and secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS).
RESULTS: Combination of weekly docetaxel and FDR gemcitabine was well tolerated: the most common treatment-related adverse events were anemia (97%), fatigue (64%) and neutropenia (55%). One patient with multiple lung and lymph node metastases died of respiratory failure after receiving four cycles of chemotherapy, and the possibility of drug-induced pneumonitis could not be completely excluded. Disease control (objective response plus stable disease) in the ITT population was achieved in 88% of patients, and the overall RR was 30% (95%CI: 15%-46%). The median PFS and OS were 4.0 (95%CI: 3.4-4.6) and 8.8 mo (95%CI: 7.8-9.8 mo), respectively.
CONCLUSION: A combination of weekly docetaxel and FDR gemcitabine showed promising antitumor activity and tolerability in previously treated, metastatic esophageal SCC.
Clinical trial; Phase II; Chemotherapy; Carcinoma, Esophageal neoplasm; Squamous cell; Docetaxel; Gemcitabine
AIM: To investigate the clinicopathologic features of patients with extra-gastrointestinal stromal tumors (EGISTs) in South Korea.
METHODS: A total of 51 patients with an EGIST were identified. The clinicopathologic features, including sex, age, location, tumor size, histology, mitotic rate, immunohistochemical features, genetic status and survival data, were analyzed.
RESULTS: The median age was 55 years (range: 29-80 years), and male:female ratio was 1:1.04. The most common site was in the mesentery (n = 15) followed by the retroperitoneum (n = 13) and omentum (n = 8). The median tumor size was 9.0 cm (range: 2.6-30.0 cm) and the median mitotic rate was 5.0/50HPF. (1/50 - 185/50). KIT was analyzed in 16, which revealed 10 cases with wild-type KIT and 6 cases with an exon 11 mutation. Among 51 patients, 31 patients had undergone surgery, and 10 had unresectable disease and had taken palliative imatinib, which resulted in 22.7 mo of progression-free survival. Of the patients who had undergone surgery, 18 did not take adjuvant imatinib, and 8 of these were categorized as “high risk” according to the risk criteria. However, the relapse-free survival was not different (P = 0.157) between two groups.
CONCLUSION: Because the biologic behaviors of GISTs differ according to the location of the tumor, a more stratified strategy is required for managing EGISTs including incorporation of molecular features.
Gastrointestinal stromal tumor; Survival; Imatinib; Risk factor; Prognostic factor
Bone marrow metastasis from solid tumors is usually accepted as not only incurable, but as fatal. Colon cancer is a relatively rare malignancy that involves the bone marrow, and to the best of our knowledge, there have been no studies in the literature reporting only bone marrow metastasis of colon cancer as the first presentation of relapse. The present study reports the case of a 74-year-old female patient treated by resection and adjuvant chemotherapy for stage IIIc colon cancer who presented with severe thrombocytopenia with intracranial hemorrhage, and the bone marrow was first and only site of metastasis. There was no evidence of skeletal metastasis. The clinical course was extremely aggressive and the patient succumbed ten days after admission, finally being diagnosed in the postmortem examination. The present study also discusses bone marrow metastasis of solid tumors, with particular respect to the diagnostic difficulties of such rare cases.
bone marrow metastasis; colon cancer; recurrence; thrombocytopenia
In Asia, the incidence of non-Hodgkin lymphoma (NHL) has increased in recent decades. Waldeyer's ring (WR) is the most common site of NHL involving the head and neck. In this study, the pathological distribution of WR-NHL and its clinical features were analyzed retrospectively.
From January 2000 through December 2010, we analyzed the medical records of 328 patients from nine Korean institutions who were diagnosed with WR-NHL.
The study group comprised 197 male and 131 female patients with a median age of 58 years (range, 14 to 89). The rate of localized disease (stage I/II) was 64.9%, and that of low-risk disease (low/low-intermediate, as defined by the International Prognostic Index) was 76.8%. Diffuse large B-cell lymphoma (DLBCL; 240 patients, 73.2%) was the most common pathologic subtype, followed by peripheral T-cell lymphoma (14 patients, 4.3%) and nasal NK/T-cell lymphoma (14 patients, 4.3%). WR-NHL occurred most frequently in the tonsils (199 patients, 60.6%). Extranodal involvement was greater with the T-cell subtype (20 patients, 42.5%) compared with the B-cell subtype (69 patients, 24.5%). Multivariate analyses showed that age ≥ 62 years, T-cell subtype, and failure to achieve complete remission were significant risk factors for overall survival.
DLBCL was found to have a higher incidence in Korea than those incidences reported by other WR-NHL studies. T-cell lymphoma occurred more frequently than did follicular lymphoma. T-cell subtype, age ≥ 62 years, and complete remission failure after first-line treatment were significant poor prognostic factors for overall survival according to the multivariate analysis.
Head and neck; Non-Hodgkin lymphoma; Diffuse large B-cell lymphoma; T-cell lymphoma
Spontaneous regression of cancer is a partial or complete disappearance of malignant tumor without specific treatment. Spontaneous regression of hepatocellular carcinoma (HCC) is a rare condition, and the mechanism underlying it is unclear. This report presents a rare case of spontaneous complete regression of HCC, as revealed by tumor markers and imaging studies. A 64-year-old Korean male patient with hepatitis B virus-associated chronic hepatitis presented with HCC. The patient had undergone right lobectomy of the liver but the cancer recurred with multiple lung and adrenal metastases after 14 months. The patient received palliative cytotoxic chemotherapy. However, there was no clinical benefit and the disease progressed. It was decided to discontinue anticancer therapy and administer only supportive care. After approximately six months, the symptoms disappeared and the HCC had completely regressed. The patient remains alive over five years after recurrence.
spontaneous regression; hepatocellular carcinoma; liver cancer; metastasis
Little is known about the clinical features of advanced gastric cancer (AGC) combined with disseminated intravascular coagulation (DIC). The main objective of this study was to determine the clinical outcome of patients with AGC complicated by DIC.
Materials and Methods
We conducted a retrospective review of 68 AGC patients diagnosed with DIC at four tertiary medical centers between January 1995 and June 2010.
Sixty eight patients were included. The median age was 55 years (range, 25 to 78 years). Nineteen patients received chemotherapy, whereas 49 patients received only best supportive care (BSC). The median overall survival (OS) of the 68 patients was 16 days (95% confidence interval [CI], 11 to 21 days). Significantly prolonged OS was observed in the chemotherapy group, with a median survival of 61 days compared to 9 days in the BSC group (p<0.001, log-rank test). Age and previous chemotherapy were another significant factors that were associated with OS in univariate analysis. In multivariate analysis, age (≥65 vs. <65; hazard ratio [HR], 0.38; 95% CI, 0.18 to 0.78; p<0.001), chemotherapy (BSC vs. chemotherapy; HR 0.31; 95% CI, 0.15 to 0.63; p<0.001), and previous chemotherapy (yes or no; HR, 0.49; 95% CI, 0.25 to 0.98; p<0.045) were consistently independent prognostic factors that impacted OS.
Our study showed that patients with AGC complicated by DIC had very poor OS, and suggested that chemotherapy might improve OS of these patients.
Stomach neoplasms; Disseminated intravascular coagulation; Drug therapy
We report here a case of oral myiasis in the Republic of Korea. The patient was a 37-year-old man with a 30-year history of Becker's muscular dystrophy. He was intubated due to dyspnea 8 days prior to admission to an intensive care unit (ICU). A few hours after the ICU admission, 43 fly larvae were found during suction of the oral cavity. All maggots were identified as the third instars of Lucilia sericata (Diptera: Calliphoridae) by morphology. We discussed on the characteristics of myiasis acquired in Korea, including the infection risk and predisposing factors.
Lucilia sericata; oral myiasis; predisposing factor; nosocomial infection
Brachial-ankle pulse wave velocity (baPWV) is known to be a good surrogate marker of clinical atherosclerosis. Atherosclerosis is a major predictor for developing neuropathy. The goal of this study was to determine the relationship between baPWV and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes.
A retrospective cross-sectional study was conducted involving 692 patients with type 2 diabetes. The correlation between increased baPWV and DPN, neurological symptoms, and neurological assessment was analyzed. DPN was examined using the total symptom score (TSS), ankle reflexes, the vibration test, and the 10-g monofilament test. DPN was defined as TSS ≥2 and an abnormal neurological assessment. Data were expressed as means±standard deviation for normally distributed data and as median (interquartile range) for non-normally distributed data. Independent t-tests or chi-square tests were used to make comparisons between groups, and a multiple logistic regression test was used to evaluate independent predictors of DPN. The Mantel-Haenszel chi-square test was used to adjust for age.
Patients with DPN had higher baPWV and systolic blood pressure, and were more likely to be older and female, when compared to the control group. According to univariate analysis of risk factors for DPN, the odds ratio of the baPWV ≥1,600 cm/sec was 1.611 (95% confidence interval [CI], 1.072 to 2.422; P=0.021) and the odds ratio in female was 1.816 (95% CI, 1.195 to 2.760; P=0.005).
Increased baPWV was significantly correlated with peripheral neuropathy in patients with type 2 diabetes.
Brachial-ankle pulse wave velocity; Diabetes mellitus, type 2; Diabetic peripheral neuropathy
This study evaluates the effectiveness of immunochemotherapy and radiation therapy in the treatment of patients with primary bone lymphoma (PBL).
We retrospectively reviewed the medical records of 33 patients with PBL who were treated at 6 medical centers in Korea from 1992 to 2010. Clinicopathological features and treatment outcomes were analyzed.
The median age of the patients participating in our study was 40 years. The most common sites of involvement were the pelvis (12.36%) and femur (11.33%). CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like regimens were administered to 20 patients (61%), and R-CHOP (rituximab plus CHOP) was administered to the remaining 13 patients (39%). The overall response rate was 89% (complete response, 76%; partial response, 12%). The overall survival (OS) of patients with solitary bone lesions was longer than that of patients with multiple bone lesions (median OS: not reached vs. 166 months, respectively; P=0.089). Addition of rituximab to CHOP did not significantly affect either OS or progression-free survival (P=0.53 and P=0.23, respectively). Combining radiation therapy with chemotherapy also did not improve the OS or progression-free survival of patients with solitary bone lesions.
Conventional cytotoxic chemotherapy remains an effective treatment option for patients with PBL. Additional benefits of supplementing chemotherapy with either rituximab or radiation therapy were not observed in this study. Further investigation is needed to characterize the role of immunochemotherapy in treating patients with PBL.
Bone lymphoma; Radiotherapy; Rituximab
We retrospectively evaluated the efficacy and safety of the modified FOLFIRI regimen in frail or elderly patients with advanced gastric cancer (AGC). We reviewed 24 frail [Eastern Cooperative Oncology Group performance status (ECOG PS) of 2] or elderly (65 years or over) patients with AGC who received the modified FOLFIRI regimen as salvage chemotherapy. Patients received irinotecan 150 mg/m2 and leucovorin (LV) 100 mg/m2 as a 2 h intravenous infusion, followed by 5-fluorouracil (5-FU) 2,000 mg/m2 as a 46 h continuous infusion. Among the 24 patients, 18 (75%) had an ECOG PS of 2, and 11 (45.8%) were aged 65 years or over. A total of 113 cycles were conducted, with a median number of 4 cycles per patient. A total of 3 patients achieved partial response (PR) and 8 demonstrated stable disease (SD). On an intent-to-treat basis, the overall response rate (RR) was 12.5% and the disease control rate (PR and SD) was 45.8%. The median time to progression (TTP) was 2 months [95% confidence interval (CI), 1.9–2.1 months] and the median overall survival (OS) was 5.4 months (95% CI, 4.1–6.7 months). Grade 3–4 hematological toxicities, including neutropenia, anemia and thrombocytopenia, were observed in 6 (25%), 4 (16.7%) and 1 (4.2%) patients, respectively. Additionally, 3 (12.5%) patients developed febrile neutropenia, of which 1 succumbed to pneumonia. Grade 3–4 gastrointestinal toxicities, including nausea, vomiting, diarrhea and mucositis, were observed in 3 (12.5%), 2 (8.3%), 1 (4.2%) and 1 (4.2%) patients, respectively. In conclusion, the modified FOLFIRI regimen as salvage chemotherapy for AGC patients over 65 years of age or with a poor PS was effective and acceptable. These results suggest that this regimen may be an effective option for frail or elderly patients with AGC.
advanced gastric cancer; FOLFIRI; elderly; poor performance status
The aim of this study was to investigate the incidence and spectrum of malignant tumors in Korean neurofibromatosis type 1 (NF1) patients.
We retrospectively reviewed 125 patients who were diagnosed with NF1 at a single institution from 1995 to 2010. The incidence, location, histologic type, and radiologic findings of malignant tumors as well as development of multiple primary tumors were analyzed.
Eighteen malignant tumors occurred in 16 patients (12.8%) among 125 Korean NF1 patients; 9 carcinomas, 8 sarcomas and 1 central nervous system (CNS) tumor. Five tumors were of nervous system origin and 13 were non-nervous system tumors. The locations of the tumors were as follow: 1 CNS, 2 lung, 3 breast, 3 stomach, 3 small bowel, 1 colon, 1 liver, 1 uterus, 1 neck, and 2 in extremities. Three malignant peripheral nerve sheath tumors (MPNSTs) occurred at the neck and extremity, and one in the liver. All three gastrointestinal stromal tumors (GISTs) had multiple tumors in the jejunum, and one MPNST and one pheochromocytoma were accompanied in two GISTs. Multiple primary tumors, benign or malignant were reported in 4 patients (25.0%), synchronously or metachronously.
Korean NF1 patients had a high risk of developing malignant tumors. The common malignant tumors in Koreans such as breast, lung and stomach cancers developed frequently in addition to the NF1-related tumors such as MPNST or GIST.
Malignant neoplasms; Neurofibromatosis 1; Korea
Bortezomib targets molecular dysregulation of nuclear factor-κB activation and cell cycle control, which are characteristic features of diffuse large B-cell lymphoma (DLBCL). We evaluated the safety and efficacy of bortezomib treatment with dose-dense cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) every 2 weeks (CHOP-14).
Untreated DLBCL patients were enrolled. A phase I dose-escalation study with 1.0, 1.3, and 1.6 mg/m2 bortezomib administration on day 1 and 4 in addition to the CHOP-14 regimen was performed to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT). Lenograstim 5 µg/kg/d was administered on day 4-13. The bortezomib dose from the phase I study was used in the phase II study.
Nine and 37 patients were enrolled in the phase I and phase II studies, respectively. The analysis of the phase II results (40 patients) included data of the 3 patients in the last MTD dose cohort of the phase I trial. During the phase I trial, no DLT was observed at any bortezomib dose; therefore, the recommended dose was 1.6 mg/m2. In phase II, the overall response rate was 95% (complete response: 80%; partial response: 15%). Nine out of the 40 patients showed grade 3 sensory neuropathy, and 22 required at least 1 dose reduction. Three patients could not complete the intended 6 cycles of treatment because of severe neuropathy.
Bortezomib plus CHOP-14 was highly effective for the treatment of untreated DLBCL patients, but in many cases, dose or schedule modification was required to reduce neurotoxicity.
Bortezomib; CHOP-14; Diffuse large B-cell lymphoma
This study was designed to retrospectively evaluate the efficacy and safety of modified FOLFOX-6 regimen in advanced gastric cancer (AGC) patients with poor performance status (PS). From January 2005 to August 2010, 23 AGC patients with poor PS who received mFOLFOX-6 as first-line chemotherapy were reviewed. Patients received 100 mg/m2 oxaliplatin and 100 mg/m2 leucovorin (LV) as a 2-h intravenous infusion on day 1, followed by 5-fluorouracil (5-FU) at 2000 mg/m2 as a 46-h continuous infusion. A total of 22 patients received more than 3 cycles of chemotherapy and were evaluable for tumor response. Seven patients achieved partial response, giving an overall response rate of 31.8%. The median time to progression and overall survival were 3.5 and 9.2 months, respectively. Grade 3–4 hematological toxicities were noted: neutropenia in four patients (17.4%), anemia in two (8.7%) and thrombocytopenia in one (4.3%). Two patients developed febrile neutropenia and one of these patients succumbed to sepsis. Grade 3–4 gastrointestinal toxicities, such as nausea, vomiting and diarrhea were observed in less than 10% of patients. Peripheral neuropathy was observed in 9 patients (39.1%). In conclusion, the mFOLFOX-6 regimen for AGC patients with poor PS was effective with acceptable toxicity. Our results suggest that this regimen may be an effective option for these patients.
advanced gastric cancer; modified FOLFOX-6; poor performance status
Primary intestinal non-Hodgkin lymphoma (NHL) is a heterogeneous disease with regard to anatomic and histologic distribution. Thus, analyses focusing on primary intestinal NHL with large number of patients are warranted.
We retrospectively analyzed 581 patients from 16 hospitals in Korea for primary intestinal NHL in this retrospective analysis. We compared clinical features and treatment outcomes according to the anatomic site of involvement and histologic subtypes.
B-cell lymphoma (n = 504, 86.7%) was more frequent than T-cell lymphoma (n = 77, 13.3%). Diffuse large B-cell lymphoma (DLBCL) was the most common subtype (n = 386, 66.4%), and extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) was the second most common subtype (n = 61, 10.5%). B-cell lymphoma mainly presented as localized disease (Lugano stage I/II) while T-cell lymphomas involved multiple intestinal sites. Thus, T-cell lymphoma had more unfavourable characteristics such as advanced stage at diagnosis, and the 5-year overall survival (OS) rate was significantly lower than B-cell lymphoma (28% versus 71%, P < 0.001). B symptoms were relatively uncommon (20.7%), and bone marrow invasion was a rare event (7.4%). The ileocecal region was the most commonly involved site (39.8%), followed by the small (27.9%) and large intestines (21.5%). Patients underwent surgery showed better OS than patients did not (5-year OS rate 77% versus 57%, P < 0.001). However, this beneficial effect of surgery was only statistically significant in patients with B-cell lymphomas (P < 0.001) not in T-cell lymphomas (P = 0.460). The comparison of survival based on the anatomic site of involvement showed that ileocecal regions had a better 5-year overall survival rate (72%) than other sites in consistent with that ileocecal region had higher proportion of patients with DLBCL who underwent surgery. Age > 60 years, performance status ≥ 2, elevated serum lactate dehydrogenase, Lugano stage IV, presence of B symptoms, and T-cell phenotype were independent prognostic factors for survival.
The survival of patients with ileocecal region involvement was better than that of patients with involvement at other sites, which might be related to histologic distribution, the proportion of tumor stage, and need for surgical resection.
intestine; non-Hodgkin lymphoma; prognosis; histopathology
Fluoropyrimidine-based combination chemotherapy, in combination with either oxaliplatin or irinotecan, has demonstrated efficacy and tolerability in treatment of advanced colorectal cancer (ACC).
Materials and Methods
Between January 2006 and December 2007, a total of 478 ACC patients were treated with combination chemotherapy in first-line settings. Combination therapies included: 5-fluorouracil, folinic acid plus oxaliplatin (FOLFOX, n=172), 5-fluorouracil, folinic acid plus irinotecan (FOLFIRI, n=95), capecitabine plus oxaliplatin (XELOX, n=155), and capecitabine plus irinotecan (XELIRI, n=56). FOLFOX and FOLFIRI were repeated every 2 weeks, whereas XELOX and XELIRI were repeated every 3 weeks until occurrence of disease progression or unacceptable toxicity, or until a patient chose to discontinue treatment.
The median age was 58 years (range, 19 to 84 years) and the median chemotherapy durations for FOLFOX, FOLFIRI, XELOX, and XELIRI were 4.9, 4.5, 5.7, and 5.4 months, respectively. Combination chemotherapy regimens were generally well tolerated. The estimated median progression-free-survival (PFS) for all patients was 6.8 months (95% confidence interval, 6.3 to 7.3 months). No statistically significant difference in PFS was found among regimens used as first-line chemotherapy. Sixty percent (n=290) of patients received second or further lines of therapy after failure.
Fluoropyrimidine-based combination chemotherapy regimens appear to be equally active and tolerable as first-line therapy for ACC.
Colonic neoplasms; Chemotherapy; Irinotecan; Oxaliplatin; Capecitabine
We performed multicenter study to define clinical characteristics of noncutaneous melanomas and to establish prognostic factors patients who received curative resection.
Of the 141 patients who were diagnosed of non-cutaneous melanoma at 4 institutions in Korea between June 1992 and May 2005, 129 (91.5%) satisfied the selection criteria.
Of the 129 noncutaneous melanoma patients, 14 patients had ocular melanoma and 115 patients had mucosal melanoma. For mucosal melanoma, anorectum was the most common anatomic site (n = 39, 30.2%) which was followed by nasal cavity (n = 30, 23.3%), genitourinary (n = 21, 16.3%), oral cavity (n = 14, 10.9%), upper gastrointestinal tract (n = 6, 4.7%) and maxillary sinus (n = 5, 3.9%) in the order of frequency. With the median 64.5 (range 4.3-213.0) months follow-up, the median overall survival were 24.4 months (95% CI 13.2-35.5) for all patients, and 34.6 (95% CI 24.5-44.7) months for curatively resected mucosal melanoma patients. Adverse prognostic factors of survival for 87 curatively resected mucosal melanoma patients were complete resection (R1 resection margin), and age > 50 years. For 14 ocular melanoma, Survival outcome was much better than mucosal melanoma with 73.3% of 2 year OS and 51.2 months of median OS (P = .04).
Prognosis differed according to primary sites of noncutaneous melanoma. Based on our study, noncutaneous melanoma patients should be treated differently to improve survival outcome.