Feasibility and effectiveness of treatment strategy of tandem high-dose chemotherapy and autologous stem cell transplantation in combination with 131 I-MIBG therapy for high-risk neuroblastoma.

This study was performed to evaluate the safety and effectiveness of tandem HDCT/ASCT combined with targeted radiotherapy using 131 I-MIBG for high-risk neuroblastoma. Patients with high-risk neuroblastoma were treated with 8 to 10 cycles of induction chemotherapy before tandem HDCT/ASCT. Patients received 131 I-MIBG treatment before the second HDCT/ASCT. Local radiotherapy and maintenance therapy were performed after tandem HDCT/ASCT. Between 2012 and 2016, 19 patients were diagnosed with high-risk neuroblastoma in our institution and 18 of them received tandem HDCT/ASCT combined with 131 I-MIBG therapy. For the first HDCT/ASCT regimen, 12 patients received busulfan/melphalan and six patients received melphalan/etoposide/carboplatin. The second HDCT included ThioCy. The median dose of 131 I-MIBG was 17.2 mCi/kg for the first eight patients, while 12 patients in the latter period of the study received reduced dose of 10.7 mCi/kg. The 5-year OS and EFS rates were 79% and 61%, respectively, for all 19 patients with high-risk neuroblastoma, and 83% and 64%, respectively, for 18 patients who completed tandem HDCT/ASCT combined with 131 I-MIBG therapy. Six patients experienced disease relapse and five patients died. Treatment-related mortality was not observed. Among 15 evaluable patients, 11 patients (73%) developed hypothyroidism, six patients (40%) had CKD, and six patients (40%) had growth failure. Hypothyroidism and growth failure were less frequent in patients who received reduced doses of 131 I-MIBG therapy. Tandem HDCT/ASCT combined with HD 131 I-MIBG therapy could be feasible for patients with high-risk neuroblastoma with acceptable toxicity profiles and favorable outcomes.

The effects of laughter therapy on mood state and self-esteem in cancer patients undergoing radiation therapy: a randomized controlled trial.

BACKGROUND: To investigate whether laughter therapy lowers total mood disturbance scores and improves self-esteem scores in patients with cancer. DESIGN/SETTING: Randomized controlled trial in a radio-oncology outpatient setting. PATIENTS: Sixty-two patients were enrolled and randomly assigned to the experimental group (n=33) or the wait list control group (n=29). INTERVENTIONS: Three laughter therapy sessions lasting 60 minutes each. OUTCOME MEASURES: Mood state and self-esteem. RESULTS: The intention-to-treat analysis revealed a significant main effect of group: Experimental group participants reported a 14.12-point reduction in total mood disturbance, while the wait list control group showed a 1.21-point reduction (p=0.001). The per-protocol analysis showed a significant main effect of group: The experimental group reported a 18.86-point decrease in total mood disturbance, while controls showed a 0.19-point reduction (p<0.001). The self-esteem of experimental group was significantly greater than that of the wait list control group (p=0.044). CONCLUSIONS: These results indicate that laughter therapy can improve mood state and self-esteem and can be a beneficial, noninvasive intervention for patients with cancer in clinical settings.

Effects of meditation on anxiety, depression, fatigue, and quality of life of women undergoing radiation therapy for breast cancer.

OBJECTIVE: To investigate the effects of meditation on anxiety, depression, fatigue, and quality of life in women who are receiving radiation therapy for breast cancer. DESIGN: Randomized, non-program controlled, parallel intervention clinical trial. SETTING: The ASAN Cancer Center located in Seoul, Korea. INTERVENTION: The subjects of this study included 102 female breast cancer patients who had undergone breast-conserving surgery; these female patients were randomized into equally assigned meditation control groups, with each group consisting of 51 patients. The test group received a total of 12 meditation therapy sessions during their 6-week radiation therapy period, and the control group underwent only a conventional radiation therapy. OUTCOME: The tools used to evaluate the effects of meditation were Hospital Anxiety and Depression scale, Revised Piper Fatigue scale, and European Organization for Research and Treatment of Cancer-Quality of Life Core-30. The results were analyzed based on the principles of intention-to-treat analysis, and, as a corollary analysis, per-protocol analysis was conducted. RESULTS: The breast cancer patients who received meditation therapy compared with the non-intervention group saw improvements in reduction of anxiety (p=.032), fatigue (p=.030), and improvement in global quality of life (p=.028). CONCLUSIONS: Based on the results of this study, an affirmation can be made that meditation can be used as a non-invasive intervention treatment for improving fatigue, anxiety, quality of life, and emotional faculties of women with breast cancer.

Randomized trial of postoperative adjuvant therapy in Stage II and III rectal cancer to define the optimal sequence of chemotherapy and radiotherapy: 10-year follow-up.

PURPOSE: To determine the optimal sequence of postoperative adjuvant chemotherapy and radiotherapy in patients with Stage II or III rectal cancer. METHODS AND MATERIALS: A total of 308 patients were randomized to early (n = 155) or late (n = 153) radiotherapy (RT). Treatment included eight cycles of chemotherapy, consisting of fluorouracil 375 mg/m(2)/day and leucovorin 20 mg/m(2)/day, at 4-week intervals, and pelvic radiotherapy of 45 Gy in 25 fractions. Radiotherapy started on Day 1 of the first chemotherapy cycle in the early RT arm and on Day 1 of the third chemotherapy cycle in the late RT arm. RESULTS: At a median follow-up of 121 months for surviving patients, disease-free survival (DFS) at 10 years was not statistically significantly different between the early and late RT arms (71% vs. 63%; p = 0.162). A total of 36 patients (26.7%) in the early RT arm and 49 (35.3%) in the late RT arm experienced recurrence (p = 0.151). Overall survival did not differ significantly between the two treatment groups. However, in patients who underwent abdominoperineal resection, the DFS rate at 10 years was significantly greater in the early RT arm than in the late RT arm (63% vs. 40%; p = 0.043). CONCLUSIONS: After the long-term follow-up duration, this study failed to show a statistically significant DFS advantage for early radiotherapy with concurrent chemotherapy after resection of Stage II and III rectal cancer. Our results, however, suggest that if neoadjuvant chemoradiation is not given before surgery, then early postoperative chemoradiation should be considered for patients requiring an abdominoperineal resection.

Postoperative chemoradiotherapy for extrahepatic bile duct cancer.

PURPOSE: To evaluate the effect of postoperative concurrent chemoradiotherapy using three-dimensional conformal radiotherapy and to identify the prognostic factors that influence survival in patients with extrahepatic bile duct cancer. METHODS AND MATERIALS: We retrospectively analyzed the data from 101 patients with extrahepatic bile duct cancer who had undergone postoperative concurrent chemoradiotherapy using three-dimensional conformal radiotherapy. Of the 101 patients, 52 (51%) had undergone complete resection (R0 resection) and 49 (49%) had microscopic or macroscopic residual tumors (R1 or R2 resection). The median radiation dose was 50 Gy. Also, 85 patients (84%) underwent concurrent chemotherapy with 5-fluorouracil. RESULTS: The median follow-up period was 47 months for the surviving patients. The 5-year overall survival rate was 34% for all patients. A comparison between patients with R0 and R1 resection indicated no significant difference in the 5-year overall survival (44% vs. 33%, p=.2779), progression-free survival (35% vs. 22%, p=.3107), or locoregional progression-free survival (75% vs. 63%, p=.2784) rates. An analysis of the first failure site in the 89 patients with R0 or R1 resection indicated isolated locoregional recurrence in 7 patients. Elevated postoperative carbohydrate antigen 19-9 level was an independent prognostic factor for overall survival (p=.001) and progression-free survival (p=.033). A total of 3 patients developed Grade 3 or greater late toxicity. CONCLUSION: Adjuvant concurrent chemoradiotherapy using three-dimensional conformal radiotherapy appears to improve locoregional control and survival in extrahepatic bile duct cancer patients with R1 resection. The postoperative carbohydrate antigen 19-9 level might be a useful prognostic marker to select patients for more intensified adjuvant therapy.

Clinical significance of NQO1 C609T polymorphisms after postoperative radiation therapy in completely resected non-small cell lung cancer.

PURPOSE: To investigate the clinical significance of NQO1 C609T polymorphisms to treatment outcome after postoperative radiation therapy in completely resected non-small cell lung cancer (NSCLC). METHODS: One hundred and sixteen, Korean-ethnic, patients who were treated with surgery and postoperative radiation therapy from February 2000 to September 2005 in Asan Medical Center (Seoul, South Korea) were analyzed. All patients received 5040cGy radiation to surgical stump, mediastinum and ipsilateral supraclavicular node. NQO1 C609T polymorphisms were examined from a peripheral blood sample in all patients. Three types of NQO1 C609T polymorphisms were designated as C/C, C/T and T/T. Chest computed tomography was routinely checked after radiation therapy at every 3 or 6 months and locoregional tumor control, distant metastasis and survival by NQO1 C609T genotype were analyzed. RESULTS: The proportion of NQO1 C609T polymorphisms was 27.6% for C/C, 53.4% for C/T and 19.0% for T/T. Most patients were men and had squamous cell carcinoma or adenocarcinoma. Median age of patients was 61 years. Major failure pattern was distant metastasis and 13 (11.2%) patients showed locoregional recurrence within the field of previous radiation therapy. Crude locoregional recurrence rate was significantly different by NQO1 genotype; 6.3% in C/C, 8.1% in C/T, and 27.3% in T/T (p=0.03), but distant metastasis was not different. Median follow-up time was 49.2 months (range: 3.4-103.5 months). Locoregional recurrence-free survival (LRRFS) was affected in T/T genotype compared with C/C or C/T genotype (p=0.01, Kaplan-Meier method), but distant metastasis-free survival (DMFS) or overall survival (OS) was not different by NQO1 genotype in univariate analysis. NQO1 genotype was also a significant factor for LRRFS (p=0.01) in multivariate analysis. Radiation-induced pneumonitis or esophagitis was tolerable in all patients and the difference by NQO1 genotype was not observed. CONCLUSIONS: NQO1 C609T polymorphisms could be a predictive factor for the locoregional tumor control after postoperative radiation therapy in completely resected NSCLC.

Concurrent chemoradiotherapy or radiotherapy alone for locally advanced cervical cancer in elderly women.

AIMS AND BACKGROUND: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy or radiotherapy alone in elderly patients with locally advanced cervical carcinoma (stage IB2-IVA). METHODS AND STUDY DESIGN: We retrospectively reviewed the medical records of 105 women aged 265 years who received radiotherapy (group I, n=61) or concurrent chemoradiotherapy (group II, n=44). Patients received a median dose of 76.4 Gy to point A, including 30-35 Gy of high-dose intracavity brachytherapy. The concurrent chemoradiotherapy group received platinum-based chemotherapy. RESULTS: The median follow-up was 65 months for surviving patients. There was no significant difference in compliance to radiotherapy between the two groups. Most acute toxicities were hematologic; acute hematologic and gastrointestinal toxicity were significantly more common in group II. Five-year overall survival and cancer-specific survival rates were, respectively, 53.5% and 66.6% in group I and 61.8% and 68.8% in group II. Performance status, comorbidity index, tumor size, and stage were independent prognostic factors for overall survival, whereas stage was the only prognostic factor for cancer-specific survival. CONCLUSIONS: The analysis showed no benefit of concurrent chemoradiotherapy with respect to overall survival and cancer-specific survival in elderly women. A prospective study is needed to determine the role of concurrent chemoradiotherapy in this population.

High-dose extended-field irradiation and high-dose-rate brachytherapy with concurrent chemotherapy for cervical cancer with positive para-aortic lymph nodes.

PURPOSE: To determine the efficacy and toxicity of extended-field radiotherapy (RT) with concurrent platinum-based chemotherapy in patients with uterine cervical carcinoma and positive para-aortic nodes. METHODS AND MATERIALS: We retrospectively reviewed the results for 33 women with Stage IB-IVB cervical cancer. Each patient had received 59.4 Gy, including a three-dimensional conformal boost to the para-aortic lymph nodes and 41.4-50.4 Gy of external beam radiotherapy to the pelvis. Each patient also underwent six or seven applications of high-dose-rate brachytherapy (median, 5 Gy to point A at each session). RESULTS: The median follow-up period of surviving patients was 39 months. The most common acute toxicity was hematologic, observed in 23 women. Severe acute and late gastrointestinal toxicity was observed in 3 and 4 patients, respectively. More than three-quarters of patients showed a complete response, encompassing the primary mass, metastatic pelvic, and para-aortic lymph nodes. Of the 33 women, 15 had no evidence of disease, 6 had persistent disease, 4 developed in-field failures, and 6 developed distant failures. The 5-year overall and disease-free survival rate was 47% and 42%, respectively. CONCLUSION: Concurrent chemoradiotherapy with extended-field radiotherapy is feasible in women with uterine cervical carcinoma and positive para-aortic lymph nodes, with acceptable late morbidity and a high survival rate, although it was accompanied by substantial acute toxicity.

Heat-induced up-regulation of NAD(P)H:quinone oxidoreductase potentiates anticancer effects of beta-lapachone.

PURPOSE: The purpose of the present study was to evaluate the efficacy of mild hyperthermia to potentiate the anticancer effects of beta-lapachone (3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione) by up-regulating NAD(P)H:quinone oxidoreductase (NQO1) in cancer cells. EXPERIMENTAL DESIGN: Effects of beta-lapachone alone or in combination with mild heating on the clonogenic survival of FSaII fibrosarcoma cells of C3H mice and A549 human lung tumor cells in vitro was determined. Effects of heating on the NQO1 level in the cancer cells in vitro were assessed using Western blot analysis for NQO1 expression, biochemical determination of NQO1 activity, and immunofluorescence microscopy for NQO1 expression. Growth of FSaII tumors in the hind legs of C3H mice was determined after treating the host mice with i.p. injection of 45 mg/kg beta-lapachone followed by heating the tumors at 42 degrees C for 1 hour every other day for four times. RESULTS: Incubation of FSaII tumor cells and A549 tumor cells with beta-lapachone at 37 degrees C reduced clonogenic survival of the cells in dose-dependent and incubation time-dependent manner. NQO1 level in the cancer cells in vitro increased within 1 hour after heating at 42 degrees C for 1 hour and remained elevated for >72 hours. The clonogenic cell death caused by beta-lapachone increased in parallel with the increase in NQO1 levels in heated cells. Heating FSaII tumors in the legs of C3H mice enhanced the effect of i.p.-injected beta-lapachone in suppressing tumor growth. CONCLUSION: We observed for the first time that mild heat shock up-regulates NQO1 in tumor cells. The heat-induced up-regulation of NQO1 enhanced the anticancer effects of beta-lapachone in vitro and in vivo.

Randomized trial of postoperative adjuvant therapy in stage II and III rectal cancer to define the optimal sequence of chemotherapy and radiotherapy: a preliminary report.

PURPOSE: We conducted a prospective randomized trial to define the optimal sequence of chemotherapy and radiotherapy of postoperative adjuvant treatment in stage II and III rectal cancer. PATIENTS AND METHODS: Three hundred eight patients were enrolled onto the study. We randomly assigned 155 to arm I (early radiotherapy group) and 153 to arm II (late radiotherapy group). Treatment included eight cycles of chemotherapy at 4-week intervals and pelvic radiotherapy of 45 Gy in 25 fractions. Radiotherapy started on day 1 of the first chemotherapy cycle in arm I and on day 1 of the third chemotherapy cycle in arm II. The chemotherapy regimen consisted of fluorouracil 375 mg/m(2)/d and leucovorin 20 mg/m(2)/d. Chemotherapy was administered for 3 days per cycle in two cycles during the period of radiotherapy and for 5 days per cycle in the remaining six cycles. RESULTS: Twenty patients in arm I and 14 in arm II were not eligible. We included 274 patients in the analysis. With a median follow-up of 37 months for surviving patients, disease-free survival was significantly prolonged in arm I compared with arm II (81% v. 70% at 4 years; P =.043). Twenty-three recurrences occurred in arm I and 38 in arm II (P =.047). Overall survival was not significantly different between arms I and II (84% v. 82% at 4 years; P =.387). CONCLUSION: Early radiotherapy with concurrent chemotherapy after resection of stage II and III rectal cancer demonstrated a statistically significant advantage for disease-free survival compared with late radiotherapy with chemotherapy.