Takayuki Ohguri

Stereotactic body radiotherapy for lung tumors in patients with subclinical interstitial lung disease: The potential risk of extensive radiation pneumonitis

PURPOSE To evaluate the toxicity and efficacy of thoracic stereotactic body radiotherapy (SBRT) in patients with subclinical interstitial lung disease (ILD). METHODS AND MATERIALS One hundred patients with 124 lung tumors were treated with SBRT at our institution according to our own protocols; patients with subclinical (untreated and oxygen-free) ILD were treated with SBRT, while those with clinical ILD (post- or under treatment) were not. The administration of 48 Gy in four fractions was used in 103 (83%) of the 124 tumors. The presence of subclinical ILD in the pre-SBRT CT findings was reviewed by two chest radiologists. The relationships between radiation pneumonitis (RP) and clinical factors were investigated. RESULTS Subclinical ILD was recognized in 16 (16%) of 100 patients. Grade 2-5 RP was recognized in 13 (13%) of 100 patients. Grade 2-5 RP was observed in three (19%) of 16 patients with subclinical ILD. Subclinical ILD was not found to be a significant factor influencing Grade 2-5 RP; however, extensive RP beyond the irradiated field, including the contralateral lung, was recognized in only three patients with subclinical ILD, and the rate of extensive RP was significantly high in the patients with subclinical ILD. Grade 4 or 5 extensive RP was recognized in only two patients with subclinical ILD. Dosimetric factors of the lungs (V5, V10, V15, V20, V25, MLD) were significantly associated with Grade 2-5 RP. The three-year overall survival and local control rates of all patients were 53% and 86%, respectively. No significant differences were seen in either overall survival or local control rates between the patients with ILD and those without ILD. CONCLUSIONS Subclinical ILD was not found to be a significant factor for Grade 2-5 RP or clinical outcomes in the current study; however, uncommon extensive RP can occur in patients with subclinical ILD.

MRI findings including gadolinium-enhanced dynamic studies of malignant, mixed mesodermal tumors of the uterus: differentiation from endometrial carcinomas

Abstract. Our objective was to evaluate the usefulness of MRI including dynamic study in differentiating malignant, mixed mesodermal tumor (MMMT) from endometrial carcinoma (EC). The MR images were reviewed in 4 patients with histologically confirmed MMMT and 11 patients with EC. Flow voids inside and/or around the tumors were seen in 2 patients with MMMT but not in any EC cases. In dynamic studies, all 4 patients with MMMT showed areas of early and persistent marked enhancement similar to that of the myometrium, mixed with areas of gradual and delayed marked enhancement. The portions showing early and persistent enhancement histologically corresponded to predominantly sarcomatous components with prominent vascularity. Ten of 11 ECs did not show such enhancement and only one showed a rapid enhancement in the early phase which was diminished in the delayed phase. The MR imaging with a gadolinium-enhanced dynamic study seems to be useful in differentiating MMMT from EC.

Cytogenetic analysis of myxoid liposarcoma and myxofibrosarcoma by array-based comparative genomic hybridisation

Aim: To investigate overall chromosomal alterations using array-based comparative genomic hybridisation (CGH) of myxoid liposarcomas (MLSs) and myxofibrosarcomas (MFSs). Materials and methods: Genomic DNA extracted from fresh-frozen tumour tissues was labelled with fluorochromes and then hybridised on to an array consisting of 1440 bacterial artificial chromosome clones representing regions throughout the entire human genome important in cytogenetics and oncology. Results: DNA copy number aberrations (CNAs) were found in all the 8 MFSs, but no alterations were found in 7 (70%) of 10 MLSs. In MFSs, the most frequent CNAs were gains at 7p21.1–p22.1 and 12q15–q21.1 and a loss at 13q14.3–q34. The second most frequent CNAs were gains at 7q33–q35, 9q22.31–q22.33, 12p13.32–pter, 17q22–q23, Xp11.2 and Xq12 and losses at 10p13–p14, 10q25, 11p11–p14, 11q23.3–q25, 20p11–p12 and 21q22.13–q22.2, which were detected in 38% of the MFSs examined. In MLSs, only a few CNAs were found in two sarcomas with gains at 8p21.2–p23.3, 8q11.22–q12.2 and 8q23.1–q24.3, and in one with gains at 5p13.2–p14.3 and 5q11.2–5q35.2 and a loss at 21q22.2–qter. Conclusions: MFS has more frequent and diverse CNAs than MLS, which reinforces the hypothesis that MFS is genetically different from MLS. Out-array CGH analysis may also provide several entry points for the identification of candidate genes associated with oncogenesis and progression in MFS.

Effect of 8-MHz radiofrequency-capacitive regional hyperthermia with strong superficial cooling for unresectable or recurrent colorectal cancer.

A well-known disadvantage of a radiofrequency-capacitive device for deep-seated tumours is preferential heating of the subcutaneous fat tissue. The authors previously developed the hyperthermia with their own external cooling unit and achieved strong superficial cooling, and reported its usefulness for the reduction of the preferential heating. The purpose of the present study was to evaluate the effect of hyperthermia with strong superficial cooling on the treatment results for unresectable or recurrent colorectal cancers. From 1986 to 2002, 44 patients with primary unresectable or locally recurrent colorectal cancer treated with thermoradiotherapy were analysed retrospectively. The patients with obesity as a subcutaneous fat thickness more than 3 cm, a high age or other serious complications did not undergo therapy. The results were compared between 17 cases with strong superficial cooling treated after 1997 (Group A) and 27 cases without strong superficial cooling treated before 1996 (Group B). Significant differences in thermometry data of Tmax, Tave and Tmin were noted between Groups A (45.3, 44.4 and 43.6°C, respectively) and B (42.9, 42.0 and 41.1°C, respectively) (p<0.01). Complete response plus partial response rates were better for Group A than for Group B (59 versus 26%, p = 0.05). Multivariate analysis by logistic regression to evaluate the effects of certain factors on complete response plus partial response was strongly correlated with strong superficial cooling (p<0.05). The median survival times for overall survival were 24.3 months for Group A and 17.1 months for Group B (p<0.05). Eight-megahertz radiofrequency-capacitive regional hyperthermia with strong superficial cooling is potentially useful for improving treatment results in unresectable or recurrent colorectal cancers.

Radiotherapy With 8-MHz Radiofrequency-Capacitive Regional Hyperthermia for Stage III Non–Small-Cell Lung Cancer: The Radiofrequency-Output Power Correlates With the Intraesophageal Temperature and Clinical Outcomes

PURPOSE To assess the efficacy of radiotherapy (RT) combined with regional hyperthermia (HT) guided by radiofrequency (RF)-output power and intraesophageal temperature and evaluate the potential contribution of HT to clinical outcomes in patients with Stage III non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS Thirty-five patients with Stage III NSCLC treated with RT plus regional HT were retrospectively analyzed. Twenty-two of the 35 patients underwent intraesophageal temperature measurements. Patients with subcutaneous fat of 2.5 cm or greater, older age, or other serious complications did not undergo this therapy. The 8-MHz RF-capacitive heating device was applied, and in all patients, both the upper and lower electrodes were 30 cm in diameter, placed on opposite sides of the whole thoracic region, and treatment posture was the prone position. The HT was applied within 15 minutes after RT once or twice a week. RESULTS All thermal parameters, minimum, maximum, and mean of the four intraesophageal temperature measurements at the end of each session and the proportion of the time during which at least one of the four intraesophageal measurements was 41 degrees C or higher in the total period of each session of HT, of the intraesophageal temperature significantly correlated with median RF-output power. Median RF-output power (>/=1,200 W) was a statistically significant prognostic factor for overall, local recurrence-free, and distant metastasis-free survival. CONCLUSIONS The RT combined with regional HT using a higher RF-output power could contribute to better clinical outcomes in patients with Stage III NSCLC. The RF-output power thus may be used as a promising parameter to assess the treatment of deep regional HT if deep heating using this device is performed with the same size electrodes and in the same body posture.

Systemic chemotherapy using paclitaxel and carboplatin plus regional hyperthermia and hyperbaric oxygen treatment for non-small cell lung cancer with multiple pulmonary metastases: Preliminary results

Purpose: The purpose of this retrospective case series was to evaluate the toxicity and efficacy of systemic chemotherapy using paclitaxel and carboplatin plus regional hyperthermia (HT) and hyperbaric oxygen treatment (HBO) for non-small-cell lung cancer (NSCLC). Materials and methods: Twenty-two patients with NSCLC with multiple pulmonary metastases intravenously received paclitaxel (50 mg/m2), carboplatin (area under the curve of 1.0–1.5) and 10% glucose weekly for 3 out of 4 weeks. Hyperthermia (HT) of the whole thoracic region was also administered weekly during intravenous infusion of carboplatin in all patients. In addition, 16 (72%) of 22 patients received hyperbaric oxygen (HBO) treatment immediately after weekly chemotherapy. A total of 107 cycles were performed in 16 patients with HBO, and 27 cycles in 6 patients without HBO. The toxicity and efficacy of these patients were retrospectively analyzed. Results: Both the hematologic and non-hematologic toxicities were mild and leucopenia/neutropenia of ≧ grade 3 was seen in one patient, while pneumonitis of ≧ grade 3 occurred in one patient. Fourteen (64%) of 22 patients had an objective response. The median time to progression of disease in all patients was 8 months and in 16 patients with HBO was 9 months. Four (44%) of 9 patients with prior chemotherapy including paclitaxel and carboplatin obtained objective responses. Conclusions: The novel combined therapy of paclitaxel and carboplatin with HT and HBO may therefore be a feasible and promising modality for treating NSCLC with multiple pulmonary metastases, and the results justify further evaluation to clarify the benefits of this treatment regimen.

Radiotherapy with 8 MHz radiofrequency-capacitive regional hyperthermia for pain relief of unresectable and recurrent colorectal cancer

Purpose: The purpose of this study was to assess the pain relief in patients with unresectable and recurrent colorectal cancer treated with radiation plus 8 MHz radiofrequency-capacitive regional hyperthermia and to identify predictors of the good outcome. Methods: Between February 1986–May 2003, 41 patients with primarily unresectable and recurrent colorectal cancer that caused pain were treated with thermoradiotherapy at the hospital and retrospectively analysed. Radiotherapy was administered with a mean total radiation dose of 56 Gy. Hyperthermia was usually applied within 30 min after radiotherapy once or twice a week. For cooling of the skin surface, the overlay boluses were applied in addition to regular boluses. The external cooling unit has been used to reinforce the cooling ability of the overlay bolus and achieve strong surface cooling to reduce the preferential heating of the subcutaneous fat tissue and treat with more RF-output in 17 patients since January 1997. Results: Pain relief was obtained in 83% of the patients. Multi-variate analysis by logistic regression to evaluate the effects of certain factors on pain relief (complete response + good response) was strongly correlated with the presence of radiating pain to leg(s) (p < 0.05). The median follow-up was 18 months. The median duration of pain relief was 7.0 months. For the 27 patients in whom the tumour temperature was estimated, the median duration of pain relief was 14.6 months for the patients with a mean average tumour temperature of >42.5°C and 5.7 months for those of <42.5°C (p < 0.05). In the 18 patients with radiating pain to leg(s), use of strong superficial cooling and the higher numbers of hyperthermia treatments were better prognostic factors for the duration of pain relief (p < 0.01 and p < 0.05, respectively). Conclusions: Radiotherapy with 8 MHz radiofrequency-capacitive regional hyperthermia provided an efficient, effective means on pain relief of treating unresectable and recurrent colorectal cancer. The duration of pain relief can be prolonged, if an adequate heating is achieved, especially in the patients with radiating pain to the leg(s).

EBM-based Clinical Guidelines for Pancreatic Cancer (2013) Issued by the Japan Pancreas Society: A Synopsis

Clinical practice guidelines for pancreatic cancer based on evidence-based medicine (2006) were published by the Japan Pancreas Society (Committee for revision of clinical guidelines for pancreatic cancer) in March 2009 in Japanese, revised to Clinical Practice Guidelines for Pancreatic Cancer based on evidence-based medicine (2009) in July 2009 in Japanese and further revised to Clinical Practice Guidelines for Pancreatic Cancer (2013) in October 2013 in Japanese. These guidelines were established according to evidence-based medicine. A total of 629 papers were collected from among 4612 reports concerning pancreatic cancer listed in PubMed and Igakuchuo Zasshi between May 2007 and January 2011. This new set of guidelines was written by members of the Committee for the Revision of Clinical Practice Guidelines for Pancreatic Cancer in the Japan Pancreas Society. The guidelines provide an algorithm for the diagnosis (Fig. 1) and treatment (Fig. 2) of pancreatic cancer and address six subjects (Diagnosis, Surgery, Adjuvant therapy, Radiation therapy, Chemotherapy and stent therapy), with 35 clinical questions and 57 recommendations.

Deep regional hyperthermia for the whole thoracic region using 8 MHz radiofrequency-capacitive heating device: Relationship between the radiofrequency-output power and the intra-oesophageal temperature and predictive factors for a good heating in 59 patients

Purpose: To assess the relationship between the radiofrequency (RF) output power and the intra-oesophageal temperature for hyperthermia of the whole thoracic region, and also to evaluate the patients’ characteristics associated with adequate heating. Materials and methods: Fifty-nine patients with thoracic cancer treated with radiotherapy plus hyperthermia were retrospectively analysed. The 8-MHz RF capacitive heating device was applied, both the upper and lower electrodes were 300 mm in diameter, placed on opposite sides of the whole thoracic region. All the patients also underwent intra-oesophageal temperature measurements. Results: All thermal parameters, Tmin, Tmax, Tave, and %T ≥ 41°C, of the intra-oesophageal temperature highly correlated with the median RF output power (p < 0.0001), and the relations were independent in the multivariable analyses including clinical characteristics (p < 0.01). The performance status showed a statistically significant association on Tmax, Tave and %T ≥ 41°C (p < 0.05). The patient age and subcutaneous fat at some levels were inversely correlated with the thermal parameters (p < 0.05). Conclusion: The RF output power was significantly correlated with the intra-oesophageal temperature; it could be used as a promising parameter to assess the efficacy of hyperthermia for the whole thoracic region. Higher intra-oesophageal temperature may be achieved in patients with good performance status, younger age and thinner subcutaneous fat.

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

Abstract 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.