Relationships between thermal dose parameters and the efficacy of definitive chemoradiotherapy plus regional hyperthermia in the treatment of locally advanced cervical cancer: data from a multicentre randomised clinical trial.

PURPOSE: To evaluate the contribution of the thermal dose parameters during regional hyperthermia (HT) treatment to the clinical outcomes in patients with cervical carcinoma (CC) who received chemoradiotherapy (CRT) plus HT. MATERIALS AND METHODS: Data from a multicentre randomised clinical trial of concurrent CRT + HT vs. CRT alone were used to evaluate the efficacy and safety of this combination therapy in the CC patients. The intrarectal temperatures of patients undergoing HT were recorded. The complete thermal data of 47 (92%) of the 51 patients in the CRT + HT group were available for the thermal analysis. Thus, 47 patients who received CRT + HT were included in the present study. RESULTS: Among the patients who received CRT + HT, a higher CEM43T90 (≥1 min) value (a thermal dose parameter) was significantly associated with better local relapse-free survival in both univariate (p = 0.024) and multivariate (p = 0.0097) analyses. The disease-free survival of the patients with higher CEM43T90 (≥1 min) values tended to be better in comparison to patients with lower CEM43T90 (<1 min) value (p = 0.071). A complete response tended to be associated with the CEM43T90 (p = 0.056). Disease-free survival, local relapse-free survival and complete response rate for patients with higher CEM43T90 (≥1) were significantly better than those for patients with CRT alone (p = 0.036, p = 0.036 and p = 0.048). CONCLUSIONS: Dose-effect relationships between thermal dose parameters and clinical outcomes were confirmed in the CC patients treated with a combination of CRT + HT. This study also confirmed that HT with lower CEM43T90 is insufficient to achieve a significant hyperthermic sensitisation to CRT.

A multicentre randomised clinical trial of chemoradiotherapy plus hyperthermia versus chemoradiotherapy alone in patients with locally advanced cervical cancer.

PURPOSE: To evaluate the effectiveness of whole-pelvic hyperthermia (HT) added to standard chemoradiotherapy (CRT) in locally advanced cervical cancer (CC), by investigating the clinical response and survival of patients treated with cisplatin-based CRT vs. CRT with HT (CRT + HT). MATERIALS AND METHODS: This study was conducted at five hospitals in Japan between September 2001 and March 2015 in patients with the International Federation of Gynecology and Obstetrics stage IB (bulky)-IVA CC undergoing definitive CRT. After giving a written informed consent, patients were randomly allocated to two treatment groups: CRT and CRT + HT group. Overall survival (OS), disease-free survival (DFS), local relapse-free survival (LRFS), complete response (CR) rate and tolerability were evaluated. RESULTS: In total, 101 patients were treated. Patient characteristics, total dose of cisplatin and radiotherapy were similar for both groups. Although not statistically significant, the 5-year OS, DFS and LRFS in the CRT + HT group (77.8%, 70.8% and 80.1%, respectively) were better than those in the CRT group (64.8%, 60.6% and 71.0%, respectively). CR was significantly more likely to be achieved in patients in the CRT + HT group than in the CRT group (88% vs. 77.6%; adjusted odds ratio, 3.993; 95% confidence interval, 1.018-15.67; p = .047). CRT + HT was well tolerated and caused no additional acute or long-term toxicity compared with CRT alone. CONCLUSIONS: HT combined with CRT improved the CR rate of CRT in patients with locally advanced CC, however, could not improve survival outcomes. Further studies in larger samples are warranted.

Expression of hypoxia-inducible factor 1α predicts clinical outcome after preoperative hyperthermo-chemoradiotherapy for locally advanced rectal cancer.

Hypoxia-inducible factor 1α (HIF-1α) is an intrinsic marker of tumor hypoxia. It has been considered that hypoxic conditions reduce radiosensitivity, but the role of HIF-1α in patients treated with preoperative therapy for rectal cancer is still unclear. The aim of this study was to evaluate the predictive value of tumor response to preoperative hyperthermo-chemoradiotherapy (HCRT) and the prognostic significance of HIF-1α expression in patients with locally advanced rectal cancer. Between 2003 and 2006, 50 patients with histologically proven rectal adenocarcinoma who underwent HCRT followed by surgery were investigated. HIF-1α expression was immunohistochemically evaluated using pre-treatment biopsies. The total radiation dose was 40-50 Gy and chemotherapy consisted of 5-FU and LV administered by continuous infusion on Day 1-5, Day 15-19, and Day 29-33 during radiotherapy. Hyperthermia treatment was performed for once a week for 2-5 sessions. The surgical operation was performed 8 weeks after HCRT and each resected specimen was graded by histological criteria of the Japanese Classification of Colorectal Carcinoma. The effects of HIF-1α on clinical outcomes were analyzed by univariate and multivariate analysis. Positive HIF-1α expression was recognized in 42.0% of samples (21/50). Resected specimens that showed pathological grades 1, 2, and 3 numbered 17, 24, and 9 cases, respectively. There were no significant differences between the HIF-1α-positive group and HIF-1α-negative group for pathological grading and pCR. Overall survival (OS) rate at 3 years in the HIF-1α-negative group was 85.2%, which was significantly better than the 60.6% in the HIF-1α-positive group. Recurrence-free survival (RFS) rate at 3 years in the HIF-1α-negative group was 82.8%, being significantly better than 47.6% in the HIF-1α-positive group. In addition, elevated HIF-1α expression was significantly correlated with recurrence-free survival and metastasis-free survival rate in multivariate analysis. HIF-1α expression might be predictive of recurrence-free survival and metastasis-free survival rate for rectal cancer patients treated with HCRT.

Results of concomitant chemoradiation for cervical cancer using high dose rate intracavitary brachytherapy: study of JROSG (Japan Radiation Oncology Study Group).

The purpose of this study was to clarify outcome for concurrent chemoradiation (CT-RT) in locally advanced cervix cancer in Japan. This is a non-randomized retrospective analysis of 226 patients treated with definitive CT-RT or radiotherapy alone (RT alone) in nine institutions between 2001 and 2003. External irradiation consisted of whole pelvic irradiation and pelvic side wall boost irradiation, using a central shield during the latter half of the treatment with the anteroposterior parallel opposing technique. The external beam irradiation was performed with 1.8 or 2 Gy per fraction. High-dose-rate intracavitary brachytherapy (HDR) was performed in all cases. In chemotherapy, platinum based drugs were used alone or in combination with other drugs such as 5FU. Grade of late complications was scaled retrospectively with CTCv2.0. Overall survival rate at 50 months of stage Ib, II and III, IV was 82% and 66% in CR-RT and 81% and 43% in R alone, respectively. Disease-free survival rate at 50 months of stage Ib, II and III, IV was 74% and 59% in CR-RT and 76% and 52% in R alone, respectively. There was no significant difference between CT-RT and RT for overall survival and disease free survival. Univariate analysis suggested that loco-regional control was better with CT-RT, but multivariate analysis could not confirm this finding. Compared to RT alone, CT-RT caused significantly more acute and late complications. Thus, late complication (grade 3-4) free survival rate at 50 month was 69% for CT-RT and 86% for RT alone (p<0.01). The therapeutic window with concomitant radiochemotherapy and HDR brachytherapy may be narrow, necessitating a close control of dose volume parameters and adherence to systems for dose prescription.

Spiritual needs in cancer patients and spiritual care based on logotherapy.

BACKGROUND: The suitability of Frankl's logotherapy for the spiritual care (psychotherapy) of cancer patients in Japan is suggested. Using Functional Assessment of Chronic Illness Therapy-Spiritual (FACIT-Sp, Japanese version), the Purpose in Life test (PIL test, Japanese version), and WHO-Subjective Inventory (WHO-SUBI, Japanese version), we attempted to elucidate the complicated structure of spirituality in cancer patients in order to identify possible approaches to their spiritual care and means of evaluating such care. MATERIALS: Two hundred and ninety-eight cancer patients participated in the study. All three tests were taken at the same time, and the results were evaluated by principal component analysis. RESULTS: It was demonstrated that all the subscales employed in the present study could be represented by a two-dimensional structure (two principal components), and that the FACIT-Sp and PIL tests have similar contents. DISCUSSION: FACIT-Sp (Japanese version) is very similar in conception to the PIL test, which was prepared in accordance with logotherapy. The results suggest that this test can serve as an adequate evaluation scale for measuring the effectiveness of spiritual care based on Frankl's logotherapy.

[Reliability and validity of the functional assessment of chronic illness therapy-spiritual (FACIT-Sp) Japanese version in cancer patients--a preliminary study].

The reliability and validity of the Functional Assessment of Chronic Illness Therapy-Spiritual well-being (FACIT-Sp), Japanese version, which was developed in the United States for a simple survey of QOL related to spirituality, was evaluated. The survey simultaneously covered FACIT-Sp and HADS, an anxiety and depression scale, using 64 cancer patients as the subjects of the study. In the evaluation of its intrinsic conformity, the Cronbach alpha reliability coefficient of the sub-scale ranged from 0.80 to 0.91 and the evaluation of validity by factor analysis indicated satisfactory factorial appropriateness. The correlation coefficients for the sub-scales were all below 0.7, indicating that each scale is independent. The correlation with HADS depression and anxiety scales was -0.54 and -0.56, respectively, showing that the emotional and spiritual scales are independent of each other. The findings suggest that The Japanese version of FACIT-Sp is associated with satisfactory reliability and validity and is an effective tool in the study of spirituality among cancer patients.

Reliability and validity of the Functional Assessment of Chronic Illness Therapy-Spiritual (FACIT-Sp) for Japanese patients with cancer.

The reliability and validity of the Japanese version of the Functional Assessment of Chronic Illness Therapy-Spiritual (FACIT-Sp) scale were assessed. This scale was developed in the United States to assess quality of life (QOL) in relation to spirituality. Two surveys were conducted on each of 306 cancer patients. In addition to the FACIT-Sp, the Hospital Anxiety and Depression Scale (HADS) was administered. Cronbach's alpha reliability coefficient, an evaluation of internal consistency, for the FACIT-Sp subscales ranged from 0.81 to 0.91. There were no significant differences between the patients evaluated using the FACIT-Sp subscale and the HADS subscale with regard to degree of religious feelings. The correlation coefficients between the FACIT-Sp and the HADS depression and anxiety scales indicated a moderate correlation. These findings suggest that the Japanese version of the FACIT-Sp scale is satisfactory in terms of reliability and validity and is a useful tool in the study of spirituality among Japanese cancer patients.