• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.4
• /
• pp.1811-1815
• /
• 2014

Background: In clinical trials with no upper age limit, the proportion of older patients is usually small, probably reflecting the more conservative approach adopted by clinicians when treating the elderly. An exploratory analysis of elderly patients in the RECORD-1 Trial showed that patients ${\geq}$ 65 y.o. had superior median PFS than overall RECORD-1 population (5.4 months and 4.9 months, respectively). We investigated the efficacy, relative benefit and safety of Everolimus (EVE) as sequential therapy after failure of VEGFr-TKI therapy for older patients with metastatic renal cell cancer (mRCC), in daily practice. Materials and Methods: 172 consecutive IRB approved patients with mRCC (median age 65, M:F 135/37, 78% clear cell) who received salvage EVE at 39 tertiary institutions between October 2009 and August 2011 were included in this analysis. Some 31% had progressed on sunitinib, 22% on sorafenib, 1% on axitinib, 41% on sequential therapy, and 5% had received other therapy. Patients with brain metastases were not included and 95% of the patients had a ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0 or 1. Previous radiotherapy was an exclusion criterion, but prior chemotherapy was permitted. Adequate organ function and hematologic parameters were mandatory. EVE administration was approved by the institutional review board at each participating institution and signed informed consent was obtained from all patients. Results: Median time of the whole cohort to last follow-up was 3.5 months (range 0.4-15.2 months). Forty four percent were continuing to take EVE at last followup. There were 86 (50%) patients ${\geq}$ 65 y.o. and 86 (50%) <65 y.o. The percentage of patients who showed PR/SD was higher in the older group than in the younger one (5.9%/61.2% vs 1.2%/46.5%, respectively). Median survival of older patients was also significantly longer (3.5 +/- 0.31 vs 3.1 +/- 0.34, hazard ratio=0.45, CI; 0.255-0.802). Analysis using Cox regression model adjusted for gender, PS, number of metastases, site of metastases, histology, smoking history and age detected an association between age and PFS (p=0.011). The frequency of adverse events in elderly patients treated with EVE was no greater than that in younger patients, although such toxicity may have had a greater impact on their quality of life. Conclusions: Older patients should not generally be excluded from accepted therapies (mTOR inhibitors after failure of VEGFr-TKI therapy) for mRCC.

• Radiation Oncology Journal
• /
• v.28 no.3
• /
• pp.125-132
• /
• 2010

Purpose: To retrospectively assess the advantages and side effects of prophylactic Paraaortic irradiation in cervical cancer patients with common iliac nodal involvement, the results for survival, patterns of failure, and treatment-related toxicity. Materials and Methods: From May 1985 to October 2004, 909 patients with cervical carcinoma received postoperative radiotherapy at the Seoul National University Hospital. Among them, 54 patients with positive common iliac nodes on pathology and negative Paraaortic node were included in the study. In addition, 44 patients received standard pelvic irradiation delivered 50.4 Gy per 28 fractions (standard irradiation group), and chemotherapy was combined in 16 of them. The other 10 patients received pelvic irradiation at a dose of 50.4 Gy per 28 fractions in addition to Paraaortic irradiation at 45 Gy per 25 fractions (extended irradiation group). In addition, all of them received chemotherapy in combination with radiation. Follow-up times for pelvic and Paraaortic irradiation ranged from 6 to 201 months (median follow-up time, 58 months) and 21 to 58 months (median follow-up time, 47 months), respectively. Results: The 4-year overall survival, disease free survival, and distant metastasis free survival in the standard irradiation group and extended irradiation group were 67.2% vs. 90.0% (p=0.291), 59.0% vs. 70.0% (p=0.568) and 67.5% vs. 90.0% (p=0.196), respectively. The most common site of first failure for the standard irradiation group was the paraaortic lymph node, while no paraaortic failure was observed in the extended irradiation group. Relatively, hematologic toxicity grade 3 or greater was common in the extended irradiation group (2/10 extended vs. 2/44 standard), while gastrointestinal toxicity of grade 3 or greater was lower (2/10 extended vs. 6/44 standard), and urologic toxicity of grade 3 or greater was observed in the standard irradition group only (0/10 vs. 3/44). Conclusion: Concurrent chemotherapy and prophylactic Paraaortic irradiation in patients with common iliac nodal involvement showed slightly improved clinical outcomes aside from increased hematologic toxicity, which was statistically insignificant. Considering the relatively small number of patients and short follow-up times, additional studies are needed to obtain more conclusive outcomes.

• Radiation Oncology Journal
• /
• v.24 no.4
• /
• pp.248-254
• /
• 2006

$\underline{Purpose}$: To evaluate acute toxicities in cervix cancer patients receiving intensity modulated whole pelvic radiation therapy (IM-WPRT). $\underline{Materials\;and\;Methods}$: Between August 2004 and April 2006, 17 patients who underwent IM-WPRT were analysed. An intravenous contrast agent was used for radiotherapy planning computed tomography (CT). The central clinical target volume (CTV) included the primary tumor, uterus, vagina, and parametrium. The nodal CTV was defined as the lymph nodes larger than 1 cm seen on CT and the contrased-enhanced pelvic vessels. The planning target volume (PTV) was the 1-cm expanded volume around the central CTV, except for a 5-mm expansion from the posterior vagina, and the nodal PTV was defined as the nodal CTV plus a 1.5 cm margin. IM-WPRT was prescribed to deliver a dose of 50 Gy to more than 95% of the PTV. Acute toxicity was assessed with common toxicity criteria up to 60 days after radiotherapy. $\underline{Results}$: Grade 1 nausea developed in 10 (58.9%) patients, and grade 1 and 2 diarrhea developed in 11 (64.7%) and 1 (5.9%) patients, respectively. No grade 3 or higher gastrointestinal toxicity was seen. Leukopenia, anemia, and thrombocytopenia occurred in 15 (88.2%). 7 (41.2%), and 2 (11.8%) patients, respectively, as hematologic toxicities. Grade 3 leukopenia developed in 2 patients who were treated with concurrent chemoradiotherapy. $\underline{Conclusion}$: IM-WPRT can be a useful treatment for cervix cancer patients with decreased severe acute toxicities and a resultant improved compliance to whole pelvic irradiation.

• Pediatric Infection and Vaccine
• /
• v.18 no.1
• /
• pp.40-47
• /
• 2011

Purpose : Norovirus infection, a common cause of community-acquired gastroenteritis, can also lead to severe illness in immunocompromised patients. We investigated clinical manifestations of norovirus infection in pediatric cancer patients. Methods : Stool specimens were collected from pediatric patients with gastrointestinal symptoms between November 2008 and September 2009 at Samsung Medical Center, Seoul, Korea. Norovirus infection was identified by reverse-transcription polymerase chain reaction (RT-PCR). A retrospective chart review was performed in pediatric cancer patients who were diagnosed with norovirus infection. Results : Ten patients were diagnosed with norovirus infection by RT-PCR in stool samples. The median age was 0.83 years (range 0.25-5.5 years) and the male to female ratio was 1.5:1 (6 males and 4 females). Underlying diseases were hematologic malignancies (4/10, 40%), neuroblastoma (4/10, 40%), and brain tumors (2/10, 20%). Three patients were infected before hematopoietic cell transplantation (HCT) and four patients after HCT. All patients had diarrhea (10/10, 100%), with a median frequency of diarrhea of 8.5 times/day (range 4-22 times/day). Median virus shedding duration was 72.5 days (range 19-299 days). Four patients with pneumatosis intestinalis were conservatively treated with bowel rest and total parenteral nutrition. One patient with severe diarrhea and bloody stool had concomitant chronic gut graft-versus-host disease (GVHD). Norovirus infection-related mortality was not observed. Conclusion : Norovirus infection can cause significant clinical manifestations with prolonged viral shedding in immunocompromised patients. Norovirus should be considered in pediatric cancer patients with severe gastrointestinal symptoms.

• Tuberculosis and Respiratory Diseases
• /
• v.52 no.4
• /
• pp.309-316
• /
• 2002

Background: To evaluate the efficacy and toxicity of combination chemotherapy using ifosfamide, cisplatin, and etoposide in patients with advanced non-small cell lung cancer(NSCLC). Materials and methods: Thirty-three patients with inoperable NSCLC(stage IIIb+IV) who had measurable diseases, and had not been treated with chemotherapeutic drugs, were enrolled in this study(from March 1995 to December 1996). The patients received ifosfamide($1500mg/m^2/day$, a full drop with Mesna on days 1-5), Cisplatin ($80mg/m^2/day$ infusion with a hydration on day 2), and Etoposide ($100mg/m^2/day$ infusion for 2 hours on days 1-3). The treatment was repeated every 4 weeks. Results: Ten patients showed a partial responses (30.3%). The overall survival time of the responders was longer than that of the non-responders (median 55 vs 22 weeks, p=0.01). The toxicities of this treatment were tolerable. Grade 3 or 4 leukopenia was observed in 21%. There was 1 death related to febrile neutropenia. The non-hematologic toxicity was mild. The relative dose intensity given to the patients was 0.86 ifosfamide, 0.87 cisplatin, and 0.89 etoposide, showing an average dose intensity of 0.87. Conclusions: A combination regimen of ifosfamide, cisplatin, and etoposide is effective and tolerable for treating advanced non-small cell lung cancer.

• Journal of Life Science
• /
• v.19 no.9
• /
• pp.1314-1320
• /
• 2009

Histone deacetylase inhibitor (HDACI) is a new promising candidate as an antineoplastic agent for the treatment of solid and hematologic malignancies. In order to evaluate cell death and to elucidate the related mechanism(s) in NSCLC cells after HDACI, sodium butyrate (SB), a representative HDACI, was used to treat H460 cells for 48 hrs. SB exposure resulted in a significant reduction of cell viability at concentrations below 7.5 mM, and about 50% of cell death occurred at 20 mM. The types of cell death induced by SB were both apoptosis and necrosis, evaluated by Annexin-V staining combined with propidium iodide. SB treatment significantly evoked G2/M cell cycle arrest and subsequently induced cell death with caspase-dependent manner. While ERK protein content was not altered after SB, phosphorylated forms of ERK were markedly reduced. Taken together, SB is significantly able to induce cell death in NSCLC cell line H460, and it is suggested that the reduction of ERK phosphorylation might be closely involved in the cancer cell death mechanism initiated by HDACI.

• Tuberculosis and Respiratory Diseases
• /
• v.55 no.1
• /
• pp.98-106
• /
• 2003

Background : To evaluate the efficacy and safety of gemcitabine and cisplatin chemotherapy in advanced non-small cell lung cancer (NSCLC). Materials and Methods : Forty patients (21 men, 19 women ; age range, 37 to 73 years; median, 63 years) with unresectable stage IIIB to IV NSCLC were evaluated. Patients received cisplatin $60mg/m^2$ (Day 1), gemcitabine $1200mg/m^2$ (Day 1 and 8) every 21 days. Eighteen patients had stage IIIB disease and 22 had stage IV. There were 28 patients of adenocarcinoma (70.0%), 11 of squamous cell carcinoma (27.5%), and one of large cell carcinoma (2.5%). Results : Of 40 patients, no patients showed complete response while 15(37.5%) showed partial response, 7(17.5%) had stable diseases, 18(45%) had progressive diseases. During a total of 195 courses of chemotherapy, grade 3 or more granulocytopenia and thrombocytopenia occured in 12.5% and 2.5% of patients respectively. Non-hematologic toxicity was mild and easily controlled. There was one case of treatment-related death by pneumomia. The median survival was 55 weeks (95% CI, 34~75weeks), and the time to progression was 19 weeks (95% CI, 16~23weeks). One year survival rate was 55% and 2 year survival rate was 10%. Conclusion : The efficacy of cisplatin and gemcitabine combination chemotherapy was acceptable in the treatment of advanced NSCLC.

• Korean Journal of Psychosomatic Medicine
• /
• v.26 no.2
• /
• pp.94-101
• /
• 2018

Objectives : The purpose of this study is to investigate the change pattern and the leading factors of delirium in the palliative ward from 2 weeks before to the end of life. Methods : From October 2015 to August 2017, a retrospective chart review was conducted on the final 180 patients of 207 patients with terminal cancer patients at the Inha University Hospital. Clinical records were collected during palliative care hospitalization. Patients were diagnosed with three subtypes of delirium through the Richmond Agitation Sedation Scale and the Nursing Delirium Screening Scale, which were evaluated daily. Results : The prevalence of delirium 13 days before death was 46%, of which 18.3% were hyperactive subtypes, 13.8% were hypoactive subtypes, and mixed subtypes were 13.8%. And hyperactive delirium gradually decreased with the approach to the end of the day, and the mixed subtype gradually increased until 4 days before the end of life. Of the patients, the day before death, 86.9% were diagnosed with delirium. In multivariate analysis, hematologic malignancy was associated with a lower rate of delirium at the end of life than gastrointestinal cancer. Overweight was associated with hyperactive, mixed, and hypoactive delirium. Conclusions : Most palliative care patients experienced delirium at the end of life. Overweight was considered as a protective factor that reduced the all subtypes of delirium at the end of life. Further prospective studies are needed to reveal the prevalence of terminal delirium, and their risk factors.

• Radiation Oncology Journal
• /
• v.22 no.3
• /
• pp.200-207
• /
• 2004

Purpose: An analysis was to compare the results of radiation alone with those of radiation with dally low dose cisplatin as a radiation sensitizer in locally advanced cervical cancer. Materials and Methods: A retrospective analysis of 59 patients diagnosed with locally advanced uterine cervix cancer between December 1996 and March 2001 was peformed. Thirty one patients received radiation alone and 28 patients received dally low dose cisplatin, as a radiation sensitizer, and radiation therapy. The median follow-up period was 34 months, ranging from 2.5 to 73 months. The radiation therapy consisted of 4500 cGy external beam irradiation to the whole pelvis (midline block after 3060 cGy), a 900$\~$l,000 cGy boost to the involved parametrium and high dose-rate intracavitary brachytherapy (a total dose of 3,000$\~$3,500 cGy/500 cGy per fraction to point A, twice per week). In the chemoradiation group, 10 mg of daily intravenous cisplatin was given daily from the 1st day of radiation therapy to the 20th day of radiation therapy. According to the FIGO classification, the patients were subdivided into 51 (86.4$\%$) and 8 (13.6$\%$) stages IIB and stage IIIB, respectively. Results: The overall 5 year survival rate was 65.65$\%$ and according to treatment modality were 56.75$\%$ and 73.42$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.180). The 5 year disease-free survival rates were 49.39$\%$ and 63.34$\%$ in the radiation alone and chemoradiatoin groups, respectively (p=0.053), The 5 year locoregional control rates were 52.34$\%$ and 73.58$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.013). The 5 year distant disease-free survival rates were 59.29$\%$ and 81.46$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.477), Treatment related hematologic toxicity were prominent in the chemoradiation group. Leukopenia $\geq$grade) occurred in 3.2$\%$and 28.5$\%$ of the radiation alone and chemoradiation groups, respectively (p=0.02). There were no statistical differences in the incidences of vesical, rectal and small bowel complications between two groups. Conclusion: Radiation therapy with low dose cisplatin did not improve the rates of survival and response rates, but did improve the rate of disease free survival and locoregional control rates In locally advanced cervical cancer. The incidence of bone marrow suppression was higher in the chemoradiation group.

• Radiation Oncology Journal
• /
• v.24 no.3
• /
• pp.171-178
• /
• 2006

[ $\underline{Purpose}$ ]: To determine the efficacy and safety of concurrent chemotherapy and radiation therapy with high-dose-rate brachytherapy for cervical cancer. $\underline{Materials\;and\;Methods}$: From January 2001 to December 2002, 30 patients with cervical cancer were treated with concurrent chemotherapy (cisplatin and 5-FU) and definitive radiation therapy. The median age was 58 (range $34{\sim}74$) year old. The pathology of the biopsy sections was squamous cell carcinoma in 29 patients and one was adenocarcinoma. The distribution to FIGO staging system was as follows: stage IB, 7 (23%); IIA, 3 (10%); IIB, 12 (40%); IIIA, 3 (10%); IIIB, 5 (17%). All patients received pelvic external beam irradiation (EBRT) to a total dose of $45{\sim}50.4\;Gy$ (median: 50.4 Gy) over $5{\sim}5.5$ weeks. Ir-192 HDR intracavitary brachytherapy (ICBT) was given after a total dose of 41.4 Gy. HDR-ICBT was performed twice a week, with a fraction point A dose of 4 Gy and median dose to point A was 28 Gy (range: $16{\sim}32\;Gy$) in 7 fractions. The median cumulative biologic effective dose (BED) at point A (EBRT+ICBT) was $88\;Gy_{10}$ (range: $77{\sim}94\;Gy_{10}$). The median cumulative BED at ICRU 38 reference point (EBRT+ICBT) was $131\;Gy_3$ (range: $122{\sim}140\;Gy_3$) at point A, $109\;Gy_3$ (range: $88{\sim}125\;Gy_3$) at the rectum and $111\;Gy_3$ (range: $91{\sim}123\;Gy_3$) at the urinary bladder. Cisplatin ($60\;mg/m^2$) and 5-FU ($1,000\;mg/m^2$) was administered intravenously at 3 weeks interval from the first day of radiation for median 5 (range: $2{\sim}6$) cycles. The assessment was performed at 1 month after completion of radiation therapy by clinical examination and CT scan. The median follow-up time was 36 months (range: $8{\sim}50$ months). $\underline{: The complete response rate after concurrent chemoradiation therapy was 93.3%. The 3-yr actuarial pelvic control rate was 87% and 3-yr actuarial overall survival and disease-free survival rate was 93% and 87%, respectively. The local failure rate was 13% and distant metastatic rate was 3.3%. The crude rate of minor hematologic complications (RTOG grade 1-2) occurred in 3 patients (10%) and one patient had suffered from severe leukopenia (RTOG grade 4) during concurrent treatment. Acute minor enterocolitis (RTOG grade 1-2) occurred in 11 patients (37%) and one patient (3%) was suffered from colon perforation during radiation therapy. Late colitis of RTOG grade 1 occurred in 5 patients (15%). Acute cystitis of RTOG grade 1 occurred in 12 patients (40%) and late cystitis of RTOG grade 2 occurred in one patient (3%). No treatment related death was seen. $\underline{Conclusion}$: The results of this study suggest that the concurrent chemoradiation therapy with HDR brachytherapy could be accepted as an effective and safe treatment for cervical cancer.