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Background: Imatinib mesylate (IM) discontinuation is under active investigation in chronic myeloid leukemia-chronic phase (CML-CP) patients with undetectable minimal residual disease (UMRD). However, limited data exist on the long-term outcomes following IM discontinuation in patients treated with frontline IM therapy. Methods: We consecutively enrolled patients with CML-CP who discontinued IM after achieving UMRD for ≥ 12 months between June 2009 and January 2013. Results: Nineteen patients (8 male, 11 female) were included. After IM discontinuation, 14 patients (74%) lost UMRD after a median of 4.0 months. Of the 14 patients with molecular relapses, 12 (86%) relapsed within the first 9 months after IM discontinuation and 2 (14%) relapsed at 20.5 and 22.8 months, respectively. No molecular relapse was observed after 2 years of IM discontinuation With a median follow-up of 58.1 months (range 23.0-66.5), the estimated UMRD persistence rate at 5 years was 23.7%. IM was readministered in all patients with molecular relapse, and 12 patients (86%) reachieved UMRD at a median of 5.3 months. A high-risk Sokal score, delayed UMRD achievement and short-term IM therapy were significantly associated with molecular relapse. Conclusion: These findings suggest that IM discontinuation in patients who achieved UMRD after frontline IM therapy resulted in favorable long-term outcomes in terms of safety and feasibility. [ABSTRACT FROM AUTHOR]

Background: Surgery alone is no longer an adequate standard of care for patients with resectable gastric cancer. Thus, research efforts should focus on which regimens are the most effective for patients with recurrent gastric cancer after combined treatment with surgery and perioperative or adjuvant chemotherapy. Methods: Patients with histologically confirmed and measurable advanced gastric cancer who showed a relapse even after fluoropyrimidine and/or cisplatin-based adjuvant chemotherapy received docetaxel (35 mg/m) intravenously on day 1 and 8 plus oxaliplatin (100 mg/m) intravenously on day 1 every 3 weeks until disease progression or unacceptable toxicity. Results: A total of 34 patients with relapsed advanced gastric cancer who had received adjuvant chemotherapy with fluoropyrimidine and/or cisplatin for a median of 6 months (range, 1-48 months) were enrolled in this trial; 22 (64.7 %) patients had been exposed to both agents. Their median age was 58 years (range, 50-68 years). The overall response rate was 55.9 % (95 % confidence interval (CI), 38.3-73.5 %), including 1 complete response and 18 partial responses. At a median follow-up duration of 28.5 months (range, 9.2-50.7 months), the median progression-free survival for all patients was 5.3 months (95 % CI, 4.4-6.1 months) and the median overall survival was 13.8 months (95 % CI, 11.1-16.4 months). The most common grade 3 or 4 hematologic and nonhematologic toxicities were neutropenia (47.1 %) and diarrhea (17.6 %), respectively. Five patients (14.7 %) experienced febrile neutropenia. Conclusions: Docetaxel and oxaliplatin combination chemotherapy was active and tolerable in patients with recurrent gastric cancer after fluoropyrimidine and/or cisplatin-based adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Background. Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of cutaneous lymphomas, accounting for less than 1% of cases of non-Hodgkin's lymphoma. Fluorine-18 fluorodeoxyglucose (F-18 FDG) positronemission tomography/computed tomography (PET/CT) findings of SPTCL before and after treatment were rarely reported. Case report. We report a case of SPTCL in which F-18 FDG PET/CT showed increased FDG accumulations in numerous subcutaneous nodules without extracutaneous disease. Contrast-enhanced CT during F-18 FDG PET/CT showed multiple minimally enhancing nodules with an infiltrative pattern in the subcutaneous layer throughout the body. Follow-up F-18 FDG PET/CT after three cycles of CHOP chemotherapy showed a complete metabolic remission of the lesions. Conclusions. F-18 FDG PET/CT is suggested to be useful in assessing the disease activity, extent and treatment response in SPTCL. [ABSTRACT FROM AUTHOR]

Background: While knowledge and risk perception have been associated with screening for second primary cancer (SPC), there are no clinically useful indicators to identify who is at risk of not being properly screened for SPC. We investigated whether the mode of primary cancer detection (i.e. screen-detected vs. non-screen-detected) is associated with subsequent completion of all appropriate SPC screening in cancer survivors. Methods: Data were collected from cancer patients treated at the National Cancer Center and nine regional cancer centers across Korea. A total of 512 cancer survivors older than 40, time since diagnosis more than 2 years, and whose first primary cancer was not advanced or metastasized were selected. Multivariate logistic regression was used to examine factors, including mode of primary cancer detection, associated with completion of all appropriate SPC screening according to national cancer screening guidelines. Results: Being screen-detected for their first primary cancer was found to be significantly associated with completion of all appropriate SPC screening (adjusted odds ratio, 2.13; 95% confidence interval, 1.36–3.33), after controlling for demographic and clinical variables. Screen-detected cancer survivors were significantly more likely to have higher household income, have other comorbidities, and be within 5 years since diagnosis. Conclusions: The mode of primary cancer detection, a readily available clinical information, can be used as an indicator for screening practice for SPC in cancer survivors. Education about the importance of SPC screening will be helpful particularly for cancer survivors whose primary cancer was not screen-detected. [ABSTRACT FROM AUTHOR]

The prognostic relevance of tumor human papillomavirus (HPV) status in anal squamous cell carcinoma (SCC) had not been previously investigated, although its relevance to cervical, head and neck SCC is known. We retrospectively evaluated outcomes in 47 patients with anal SCC treated with combined chemoradiotherapy (CCRT) and determined tumor HPV status by HPV DNA chip method and p16 expression by immunohistochemistry (IHC) from paraffin-embedded tumor tissues. The median age was 65 years (range, 44-90 years). Sixteen (34%) patients were diagnosed with T stage 3 to 4, and 18 (38%) patients had regional nodal disease (N-positive). Thirty-five (75%) patients were HPV positive, and 31 (66%) patients were genotype 16 (HPV16-positive). Thirty-nine (83.0%) patients were positive for p16. After median follow-up of 51.7 months (range, 5.1-136.0 months), HPV16-positive group had significantly better 4-year progression-free survival (PFS, 63.1% vs. 15.6%, p < 0.001) and overall survival (84.6% vs. 39.8%, p = 0.008) than HPV genotype 16 negative (HPV16-negative) group. Patients with p16-positive tumor also had a better 4-year PFS (52.5% vs. 25.0%, p = 0.014) than those with p16-negative tumor. In multivariate analysis for PFS, N-positive and HPV16-negative were independent prognostic factors for shorter PFS. Comparing patterns of failure, time to loco-regional failure was statistically superior in HPV16-positive over HPV16-negative groups ( p = 0.006), but time to systemic failure was not different ( p = 0.098). Tumor HPV genotype 16 status is a prognostic and predictive factor in anal SCC treated with CCRT, and p16 expression determined by IHC might be advocated as a surrogate biomarker of HPV integration in anal SCC. Further studies are warranted. [ABSTRACT FROM AUTHOR]

The sternum is known as a relatively common site for bone metastases by a variety of malignant neoplasms. The usual finding is increased radiotracer uptake on bone scintigraphy, and cold metastasis is distinctly unusual. In addition, total nonvisualization of the sternum presenting as bone metastasis is extremely rare. We describe two cases with similar findings (absent sternum showing no activity of the sternal segments on bone scintigraphy), which corresponded to metastatic involvement. These findings were shown to be the first manifestation of hepatocellular carcinoma in one patient and bone metastasis in another patient with ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: End-of-dose failure is commonly observed as therapeutic levels of sustained-release opioids fall. However, little is known about using these medications for cancer pain control. To determine the dosing frequency of sustained-release opioids (morphine, oxycodone, and transdermal fentanyl) and the prevalence of end-of-dose failure in clinical practice, a patient-reported survey was performed.Methods: A multicenter survey was conducted in 56 hospitals in Korea between June and November 2008.Results: The study enrolled 1,097 cancer outpatients who were prescribed oral sustained-release opioids (morphine or oxycodone) or transdermal fentanyl. Of the oral sustained-release opioid patients, 67.0% took oral sustained-release oral opioids twice daily, while 26.2% took them more than twice daily. Of the transdermal fentanyl patients, 88.8% wore the patch for 72 h. Of the enrolled patients, 48.3% experienced worsening pain just before the next sustained-release opioid dose, and 36.8% of these patients took medication earlier than the prescribed dosing schedule. Patients felt that oral sustained-release opioids gave adequate pain control lasting an average of 9.6 h, versus an average of 62.9 h for transdermal fentanyl.Conclusion: This survey demonstrated that sustained-release opioids are used by patients in a manner that is inconsistent with standard recommendations. End-of-dose failure is suggested to explain increased dosing frequency, and patients reported that adequate pain relief lasted for less time than was stated in the manufacturers' prescription recommendation. [ABSTRACT FROM AUTHOR]

The differentiation of promyelocytic leukemic cells into mature cells is the major strategy for drug-based treatment of leukemia. Higher efficient methods to differentiate promyelocytic leukemic cells have been developed using various differentiation inducers including interferon-alpha, interleukin-4, tumor necrosis factor-alpha (TNF-alpha), and dimethyl sulfoxide (DMSO) as a single agent or in combination with each other. Here, we show that a combination of TNF-alpha with DMSO shows a synergic effect on HL-60 cell differentiation through the activation of ERK pathway. TNF-alpha enhanced CD11b expression and percent of cell population in the G1 phase induced by DMSO, which are hallmarks for HL-60 cell differentiation. Inhibition of ERK pathway abolished the synergic effect of TNF-alpha in combination with DMSO on HL-60 differentiation, but the inhibition NF-kappaB pathway did not. These results suggest that TNF-alpha synergistically increases DMSO-induced differentiation of HL-60 cells through the activation of ERK/MAPK-signaling pathway. [ABSTRACT FROM AUTHOR]

Tumor-infiltrating immune cells perform a crucial function in host immune reactions against diffuse large B-cell lymphoma (DLBCL). In this study, we have identified a subset of tumor-infiltrating FOXP3-positive regulatory T cells (Tregs) in the initial DLBCL biopsy specimens, and have evaluated their prognostic significance. Ninety six patients with DLBCL were evaluated retrospectively. The pattern of FOXP3 protein expression was evaluated using standard immunohistochemistry in paraffin-embedded tissue samples. Sixty seven of all 96 specimens were stained with antibodies for CD-10, bcl-6 and MUM1 via tissue microarray (TMA) to classify the cases into a germinal center B-cell like (GCB) group and a non-GCB group. The median overall survival (OS) was 28 months. As compared with the others, the patients with higher percentages of FOXP3-positive Tregs on initial tumor biopsy evidenced a significantly longer OS (p = 0.003). Patients classified into the GCB group evidenced a significantly longer OS as compared with the non-GCB group (p = 0.008). When the prognostic factors were evaluated via a multivariate model, the international prognostic index and the percentage of infiltrating FOXP3-positive Tregs in the initial biopsy were identified as independent predictors of OS. In conclusion, the presence of an increased percentage of FOXP3-positive Tregs in DLBCL is predictive of better prognoses. [ABSTRACT FROM AUTHOR]

Background: Drug-induced nephrotic syndrome (NS) can be resolved by eliminating the causative agents. However, patients with metastatic cancer have not been previously reported to achieve complete recovery from anticancer drug-induced NS after discontinuation of treatment, because many patients die of cancer progression before NS is restored.Case Presentation: A 67-year-old man presented with edema of both lower extremities. He received pazopanib therapy for recurrent metastatic renal cell carcinoma (mRCC) for 17 months. Laboratory examinations revealed 7484.58 mg/day of 24-h urine protein, 434 mg/dL of serum cholesterol, and 2.9 g/dL of serum albumin. He was diagnosed with NS, and pazopanib treatment was discontinued. Four months later, he completely recovered from NS. He was then treated with temsirolimus and nivolumab sequentially for > 26 months. Pazopanib was re-introduced following disease progression, and demonstrated antitumor effects for 7 months without NS recurrence.Conclusion: Pazopanib-induced NS can occur late in patients with mRCC, and its subsequent discontinuation can enable patients to completely recover from its adverse effects. Moreover, pazopanib treatment may be re-introduced without the recurrence of NS. [ABSTRACT FROM AUTHOR]