Salvage Re-irradiation with Intensity-modulated Radiotherapy, Chemotherapy Combined with Hyperthermia for Local Recurrence of Nasopharyngeal Carcinoma After Chemoradiotherapy.

A sufficient dose of radiation is difficult to administer in re-irradiation for local recurrence of cancer after radiotherapy because of the dose limitation to organs at risk. Re-irradiation cases also include radioresistant tumors that are difficult to control locally, and their prognosis is poor in general. The effect of re-irradiation using intensity-modulated radiotherapy (IMRT) has recently been reported to significantly reduce the dose to organs at risk, and the efficacy of hyperthermia has been reported for radioresistant tumors. We report a case of local recurrence after concurrent chemoradiotherapy treated with salvage re-irradiation using IMRT and chemotherapy combined with hyperthermia in a patient with nasopharyngeal carcinoma, and include a discussion of the literature.

Pembrolizumab-induced Radiation Recall Pneumonitis After the Resolution of Typical Asymptomatic Radiation Pneumonitis.

Radiation recall pneumonitis is a phenomenon in which a recall-triggering drug induces an acute inflammatory reaction in the lungs, corresponding to a previously irradiated area. Radiation recall reactions have been reported to occur following treatments with various cytotoxic anticancer agents and molecular-targeting drugs; however, only a few reports have described immune checkpoint inhibitor-induced radiation recall pneumonitis. We report a case of radiation recall pneumonitis induced by pembrolizumab in a patient with the postoperative local recurrence of non-small cell lung cancer. This case demonstrated that pembrolizumab might cause severe radiation recall pneumonitis, even after typical radiation pneumonitis has been resolved.

Alteration in tumoural PD-L1 expression and stromal CD8-positive tumour-infiltrating lymphocytes after concurrent chemo-radiotherapy for non-small cell lung cancer.

BACKGROUND: Consolidation treatment with an anti-PD-L1 antibody, durvalumab, following concurrent chemo-radiotherapy (cCRT) has become a new standard of care for locally advanced non-small cell lung cancer (NSCLC). The rationale of PD-L1 blockade after cCRT is based on preclinical evidence suggesting that chemotherapy and radiotherapy up-regulate tumoural PD-L1 expression, which has not been shown in clinical studies. METHODS: To examine alteration in tumoural PD-L1 expression (tumour proportion score, TPS) and density of stromal CD8-positive tumour-infiltrating lymphocytes (CD8 + TILs) after cCRT, paired NSCLC samples obtained before and after cCRT were reviewed in comparison with those obtained before and after drug therapy. RESULTS: PD-L1 expression was significantly up-regulated after cCRT (median TPS, 1.0 at baseline versus 48.0 after cCRT; P < 0.001), but not after drug therapy. There was no significant correlation between baseline TPS and post-cCRT TPS. CD8 + TIL density was significantly increased after cCRT (median, 10.6 versus 39.1; P < 0.001), and higher post-cCRT CD8 + TIL density was associated with a higher pathologic response and with a favourable survival (P = 0.019). CONCLUSION: Tumoural PD-L1 expression was up-regulated after cCRT, which provides pathologic rationale for PD-L1 blockade following cCRT to improve prognosis. Stromal CD8 + TIL density was also increased after cCRT, and higher post-cCRT CD8 + TIL density was a favourable prognostic indicator.

The usefulness of mobile insulator sheets for the optimisation of deep heating area for regional hyperthermia using a capacitively coupled heating method: phantom, simulation and clinical prospective studies.

PURPOSE: To evaluate the feasibility and efficacy of deep regional hyperthermia with the use of mobile insulator sheets in a capacitively coupled heating device. MATERIALS AND METHODS: The heat was applied using an 8-MHz radiofrequency-capacitive device. The insulator sheet was inserted between the regular bolus and cooled overlay bolus in each of upper and lower side of the electrode. Several settings using the insulator sheets were investigated in an experimental study using an agar phantom to evaluate the temperature distributions. The specific absorption rate (SAR) distributions in several organs were also computed for the three-dimensional patient model. In a clinical prospective study, a total of five heating sessions were scheduled for the pelvic tumours, to assess the thermal parameters. The conventional setting was used during the first, third and fifth treatment sessions, and insulator sheets were used during the second and fourth treatment sessions. RESULTS: In the phantom study, the higher heating area improved towards the centre when the mobile insulator sheets were used. The subcutaneous fat/target ratios for the averaged SARs in the setting with the mobile insulator (median, 2.5) were significantly improved compared with those in the conventional setting (median, 3.4). In the clinical study, the thermal dose parameters of CEM43°CT90 in the sessions with the mobile insulator sheets (median, 1.9 min) were significantly better than those in the sessions using a conventional setting (median, 1.0 min). CONCLUSIONS: Our novel heating method using mobile insulator sheets was thus found to improve the thermal dose parameters. Further investigations are expected.

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.

Cardiac and respiratory effects of deep regional hyperthermia using an 8 MHz radiofrequency-capacitive device on patients with cancer.

PURPOSE: Hyperthermia (HT), an adjuvant therapy for variable cancers, may cause physiological changes in the patients, which may lead to cardiovascular problems. Among various HT treatments, the physiological effects of deep regional HT are still unclear. We examined the physiological alterations throughout deep regional HT to improve the HT safety. MATERIALS AND METHODS: Thirty-one patients (age: 61 ± 12 years) with cancer received HT in the thoracic or upper abdominal regions using an 8-MHz radiofrequency-capacitive-device for 50 min. Rectal temperature (Trec), systolic and diastolic blood pressures (SBP and DBP), pulse rate (PR), respiratory rate (RR), percutaneous oxygen saturation (SpO2) and sweating volume were evaluated throughout HT. RESULTS: At 50 min after starting HT, Trec, PR and RR were significantly increased compared with the baseline values (Trec: 38.2 ± 1.4 vs. 36.3 ± 0.8 °C, p < 0.001, PR: 104 ± 15 vs. 85 ± 16 bpm, p < 0.05, RR: 23 ± 3 vs. 21 ± 3/min, p < 0.05). Although the average SBP and DBP were both stable during HT in a recumbent position, these values dropped significantly in a standing position (SBP: 113 ± 16 vs. 127 ± 18 mmHg, p < 0.001, DBP: 70 ± 12 vs. 75 ± 13 mmHg, p < 0.01). The total amount of sweating was 356 ± 173 g/m2 on average. CONCLUSIONS: Deep regional HT increased the deep body temperature and resulted in an increase of sweating with peripheral vasodilatation. Consequently, a significant reduction in BP would be induced on standing after HT. Careful attention is needed for patients receiving HT, especially when standing after HT.

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.

Efficacy of hyperbaric oxygen therapy combined with mild hyperthermia for improving the anti-tumour effects of carboplatin.

PURPOSE: The aim of this study was to evaluate the effects of hyperbaric oxygen therapy (HBO) on the enhancement of hyperthermic chemosensitisation to carboplatin at mild temperatures in experimental tumours. METHODS: SCCVII carcinoma in C3H/He mice was used to assess tumour growth delay. The mice received intraperitoneal injections of carboplatin. For HBO treatment, the mice were exposed to HBO at 2.0 atmospheres of absolute oxygen for 60 min. For mild hyperthermia (HT), treatment at 41.5 °C for 30 min was performed. The tumour tissue pO2 levels were measured with a digital pO2 monitor during and immediately after treatment. RESULTS: The average time taken to reach a threefold relative tumour size was significantly longer after treatment with carboplatin combined with mild HT and HBO than after treatment with carboplatin and mild HT. The relative sizes of the tumours after the combined treatment were smallest when the treatment sequence was carboplatin, mild HT, and HBO. The tumour tissue pO2 values were significantly higher immediately after mild HT followed by HBO than immediately after HBO followed by mild HT. The tumour tissue pO2 levels during mild HT and HBO generally increased, although the patterns of the increases varied. CONCLUSION: The administration of HBO increased the effects of hyperthermic chemosensitisation to carboplatin at mild temperatures on experimental tumours, particularly when given in the sequence of carboplatin, mild HT, and HBO, a finding that supports previous clinical outcomes for a novel combined therapy using carboplatin plus HT and HBO.

Definitive radiotherapy plus regional hyperthermia for high-risk and very high-risk prostate carcinoma: Thermal parameters correlated with biochemical relapse-free survival.

PURPOSE: The aim of this study was to assess the efficacy of definitive radiotherapy (RT) plus regional hyperthermia (HT) and investigate the potential contribution of HT to clinical outcomes in patients with prostate carcinoma. MATERIALS AND METHODS: Following our institution's treatment protocol, HT was combined with RT to improve clinical outcomes in selected patients with high-risk or very high-risk prostate cancer. Data from 82 patients treated with RT plus HT and 64 patients treated with RT alone were retrospectively analysed. RESULTS: Median follow-up duration was 61 months. The 5-year biochemical disease-free survival (bDFS) rate for the 82 patients treated with RT plus HT was 78%, whereas bDFS for the 64 patients treated with RT alone was 72%; this difference was not significant. Among the 75 patients treated with RT plus HT who underwent intra-rectal temperature measurements, higher thermal parameters were significant prognostic indicators of improved bDFS by univariate analysis. A higher CEM43 °CT90 thermal parameter and a T stage of T1-2 were significant prognostic factors based on multivariate analysis. The 5-year bDFS rates for the 40 patients with a higher CEM43 °CT90 and the 64 patients treated with RT alone were significantly different, whereas 5-year bDFS for the 35 patients with a lower CEM43 °CT90 and the 64 patients treated with RT alone were not. CONCLUSIONS: The addition of HT with higher thermal parameters to RT may improve bDFS for patients with high-risk or very high-risk prostate cancer. These findings also demonstrate the importance of careful selection of treatable patients with higher thermal parameters.

Definitive radiotherapy plus regional hyperthermia for high-risk and very high-risk prostate carcinoma: Thermal parameters correlated with biochemical relapse-free survival.

PURPOSE: The aim of this study was to assess the efficacy of definitive radiotherapy (RT) plus regional hyperthermia (HT) and investigate the potential contribution of HT to clinical outcomes in patients with prostate carcinoma. MATERIALS AND METHODS: Following our institution's treatment protocol, HT was combined with RT to improve clinical outcomes in selected patients with high-risk or very high-risk prostate cancer. Data from 82 patients treated with RT plus HT and 64 patients treated with RT alone were retrospectively analysed. RESULTS: Median follow-up duration was 61 months. The 5-year biochemical disease-free survival (bDFS) rate for the 82 patients treated with RT plus HT was 78%, whereas bDFS for the 64 patients treated with RT alone was 72%; this difference was not significant. Among the 75 patients treated with RT plus HT who underwent intra-rectal temperature measurements, higher thermal parameters were significant prognostic indicators of improved bDFS by univariate analysis. A higher CEM43 °CT90 thermal parameter and a T stage of T1-2 were significant prognostic factors based on multivariate analysis. The 5-year bDFS rates for the 40 patients with a higher CEM43 °CT90 and the 64 patients treated with RT alone were significantly different, whereas 5-year bDFS for the 35 patients with a lower CEM43 °CT90 and the 64 patients treated with RT alone were not. CONCLUSIONS: The addition of HT with higher thermal parameters to RT may improve bDFS for patients with high-risk or very high-risk prostate cancer. These findings also demonstrate the importance of careful selection of treatable patients with higher thermal parameters.

Radiotherapy for thoracic tumors: association between subclinical interstitial lung disease and fatal radiation pneumonitis.

BACKGROUND: We evaluated the association between subclinical interstitial lung disease (ILD) and fatal radiation pneumonitis (RP) in patients with thoracic tumors treated with thoracic radiotherapy (RT). METHODS: Sixty-two consecutive patients with thoracic tumors treated with thoracic RT were retrospectively analyzed. According to our protocols, patients with subclinical ILD (untreated and asymptomatic) were considered to be indicated for thoracic RT, while patients with clinical ILD (post- or during treatment) were not considered candidates for thoracic RT. The presence, extent and distribution of subclinical ILD on CT findings at pre-thoracic RT were reviewed and scored by two chest radiologists. The relationships between RP and clinical factors, including subclinical ILD, were investigated. RESULTS: Subclinical ILD was recognized in 11 (18 %) of the 62 patients. Grade 2-5 RP was recognized in eight (13 %) of the 62 patients, with Grade 5 in three patients and Grade 2 in five patients. Grade 2-5 RP was observed in four (36 %) of the 11 patients with subclinical ILD. Subclinical ILD was found to be a significant factor influencing the development of Grade 2-5 RP (p = 0.0274). Subclinical ILD tended to be significant for the occurrence of Grade 5 RP (p = 0.0785). Regarding the CT score, more extensive ILD (bilateral fibrosis in multiple lobes) was recognized in two of the three patients with Grade 5 RP. CONCLUSIONS: In this study, fatal RP tended to be more common in the patients with subclinical ILD. In particular, the presence of extensive fibrosis on CT may be a contraindication for thoracic RT.

A Case Report of Long-Term Survival Achieved by Nivolumab and Hyperthermia With Multiple Local Therapies for the Peritoneal Dissemination of Gastric Cancer.

A 60-year-old male with recurrent metastatic gastric cancer achieved long-term survival with nivolumab, hyperthermia, and local multisite therapy. The patient had a history of multiple relapses despite receiving standard treatment. After the failure of multiple lines of chemotherapy, nivolumab and hyperthermia were initiated. During this combination therapy, local treatments including surgery and radiation therapy were administered to treat the progressive disease. Remarkably, the patient achieved more than five years of overall survival time after starting nivolumab and external repeated hyperthermia with local therapies and has shown no measurable disease on imaging for the past 24 months. This case suggests that a combination of nivolumab, hyperthermia, and local therapies may offer a potential therapeutic strategy for patients with advanced gastric cancer.

Prophylactic Effect of Clarithromycin on Radiation Pneumonitis in IMRT for Lung Cancer.

BACKGROUND/AIM: To evaluate the association between prophylactic administration of clarithromycin (CAM) and the development of radiation pneumonitis (RP) in patients treated with intensity modulated radiation therapy (IMRT) for lung cancer. PATIENTS AND METHODS: A total of 89 patients who underwent definitive or salvage IMRT for lung cancer were retrospectively evaluated. The median total and daily doses were 60 Gy and 2 Gy, respectively. A total of 39 patients (44%) received CAM for a median of three months after the start of IMRT. The relationship between the development of RP and certain clinical factors was analyzed. RESULTS: RP of Grade ≥2 was recognized in 10 (11%) patients; Grade 2 in six patients and Grade 3 in four patients. The incidence of Grade ≥2 RP was 3% (1/39) in patients treated with CAM, which was significantly lower than that of 18% (9/50) in patients without CAM. The median lung V20 and V5 in the 10 patients with RP Grade ≥2 were 24% and 46%, respectively, compared with 18% and 37% in the 79 patients with RP Grade 0-1, and the differences were significant. Durvalumab administration after IMRT was also a significant factor for RP Grade ≥2. CONCLUSION: Prophylactic administration of CAM may reduce Grade ≥2 RP in patients treated with IMRT for lung cancer. Therefore, further clinical trials are warranted.

Intensity-Modulated Radiotherapy with Regional Hyperthermia for High-Risk Localized Prostate Carcinoma.

BACKGROUND: The purpose of this study was to evaluate the efficacy and toxicity of adding regional hyperthermia to intensity-modulated radiotherapy (IMRT) plus neoadjuvant androgen deprivation therapy (ADT) for high-risk localized prostate carcinoma. METHODS: Data from 121 consecutive patients with high-risk prostate carcinoma who were treated with IMRT were retrospectively analyzed. The total planned dose of IMRT was 76 Gy in 38 fractions for all patients; hyperthermia was used in 70 of 121 patients. Intra-rectal temperatures at the prostate level were measured to evaluate thermal dose. RESULTS: Median number of heating sessions was five and the median total thermal dose of CEM43T90 was 7.5 min. Median follow-up duration was 64 months. Addition of hyperthermia to IMRT predicted better clinical relapse-free survival. Higher thermal dose with CEM43T90 (>7 min) predicted improved biochemical disease-free survival. The occurrence of acute and delayed toxicity ≥Grade 2 was not significantly different between patients with or without hyperthermia. CONCLUSIONS: IMRT plus regional hyperthermia represents a promising approach with acceptable toxicity for high-risk localized prostate carcinoma. Further studies are needed to verify the efficacy of this combined treatment.

Retrospective analysis of prognosis using the Gynecology Oncology Group score of stage IB-IIA node negative uterine cervical cancer after radical hysterectomy and trachelectomy.

There is currently controversy regarding the criteria for low and intermediate risk of cervical cancer (CC) after surgery. In the present study, the Gynecology Oncology Group (GOG) score was used to detect intermediate risk. Adjuvant radiotherapy was applied in the case of a GOG score >120. The present study aimed to evaluate the validity of the recurrence risk classification using the GOG score for stage IB-IIA node-negative CC. All cases of stage IB-IIA node-negative CC who underwent radical surgery between February 2007 and December 2015 were retrospectively reviewed. The GOG scores were determined from clinical and pathological findings and accordingly, subjects were divided into 4 groups: A, ≤40; B, >40 and ≤70; C, >70 and ≤120; and D, >120. Overall survival (OS) and recurrence-free survival (RFS) curves were generated using the Kaplan-Meier method. The log-rank test produced an estimated P-value by comparing the OS and RFS of group A (low-score group) with those of others. The present study included 61 patients (mean age, 47.82 years; age range, 22-76 years) and the median follow-up was 79 (39-149) months. Of these, 60 patients were observed for at least 60 months. During the follow-up period, the OS and RFS rates of group C were 94.7 and 84.2%, respectively, while those of group D were 100 and 91.7%, respectively; the OS and RFS of groups A and B were 100%. Log-rank tests for all OS and RFS indicated no significant differences compared to group A. It was indicated that a GOG score ≤70 does not require adjuvant therapy; however, a GOG score >70 requires consideration of adjuvant therapy based on the risk factors which constitute the score.

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, T(min), T(max), T(ave), 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 T(max), T(ave) 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.

Optimization of the Clinical Setting Using Numerical Simulations of the Electromagnetic Field in an Obese Patient Model for Deep Regional Hyperthermia of an 8 MHz Radiofrequency Capacitively Coupled Device in the Pelvis.

Background: The purpose of this study was to evaluate the effectiveness of the clinical setting for deep regional hyperthermia of an 8 MHz radiofrequency (RF) capacitively coupled device in the pelvis by using numerical simulations of the electromagnetic field. Methods: A three-dimensional patient model of cervical cancer of the uterus in an obese patient was reconstructed with computed tomography data. The specific absorption rate (SAR) and temperature distributions among the various heating settings were evaluated using numerical simulations. Results: The averaged SAR value of the deep target tumor was similar between with or without overlay boluses (OBs), and that of the subcutaneous fat (SF) at the edges of cooling boluses with OBs was lower than that of the SF without OBs. The use of OBs reduced the overheating of the SF. The 0.5% salt solution in the OB produced the least overheated areas outside the deep target tumor compared with the other concentrations. The insertion of the intergluteal cleft (IGC) bolus could improve the temperature concentration of the deep target tumor. Conclusions: The use of OBs and the salt solution concentration in the OB were important to optimize the temperature distribution. IGC bolus might contribute to temperature optimization. Further studies with individualized numerical simulations in each patient are expected.

Early volume reduction of the hippocampus after whole-brain radiation therapy: an automated brain structure segmentation study.

PURPOSE: To assess atrophy differences among brain regions and time-dependent changes after whole-brain radiation therapy (WBRT). MATERIALS AND METHODS: Twenty patients with lung cancer who underwent both WBRT and chemotherapy (WBRT group) and 18 patients with lung cancer who underwent only chemotherapy (control group) were recruited. Three-dimensional T1WI were analyzed to calculate volume reduction ratio after WBRT in various brain structures. The volume reduction ratio of the hippocampus was compared among following 3 periods: 0-3, 4-7, and 8-11 months after WBRT. RESULTS: The volume reduction ratio of the hippocampus was significantly higher in the WBRT group than in the control group (p < 0.05). In WBRT group, the volume reduction ratio of the hippocampus was significantly higher than that of the cortex and white matter (p < 0.05). There were significant differences in the volume reduction ratio between of 0-3 months and that of 4-7 months (p = 0.02) and between 4-7 months and that of 8-11 months (p = 0.01). CONCLUSION: The hippocampus is more vulnerable to the radiation compared with other brain regions and may become atrophic even in the early stage after WBRT.

Pediatric nasopharyngeal cancer with repeated oligometastases involving the bone, liver and distant lymph nodes who achieved cure after radiotherapy.

Systemic chemotherapy is a standard treatment for Stage IVc nasopharyngeal carcinoma (NPC). Stage IVc NPC patients with oligometastases have a better prognosis, and local therapy has an important role in further development of the disease. However, the efficacy of local therapy to the metastases in patients with multiple-site and/or multiple-organ metastases is limited due to the aggressive behavior of the tumor. We report a NPC case in a pediatric patient with repeated oligometastases involving the bone, liver and distant lymph nodes who achieved 10-year disease free status after initial chemotherapy and radiotherapy to all the metastases. This very rare case demonstrated that radiotherapy to oligometastatic lesions have a potential to cure repeated oligometastases which involved multiple-organ metastases in a pediatric NPC with stage IVc.

Predictive gamma passing rate for three-dimensional dose verification with finite detector elements via improved dose uncertainty potential accumulation model.

PURPOSE: We aim to develop a method to predict the gamma passing rate (GPR) of a three-dimensional (3D) dose distribution measured by the Delta4 detector system using the dose uncertainty potential (DUP) accumulation model. METHODS: Sixty head-and-neck intensity-modulated radiation therapy (IMRT) treatment plans were created in the XiO treatment planning system. All plans were created using nine step-and-shoot beams of the ONCOR linear accelerator. Verification plans were created and measured by the Delta4 system. The planar DUP (pDUP) manifesting on a field edge was generated from the segmental aperture shape with a Gaussian folding on the beam's-eye view. The DUP at each voxel ( u ) was calculated by projecting the pDUP on the Delta4 phantom with its attenuation considered. The learning model (LM), an average GPR as a function of the DUP, was approximated by an exponential function a GPR u = e - q u to compensate for the low statistics of the learning data due to a finite number of the detectors. The coefficient q was optimized to ensure that the difference between the measured and predicted GPRs ( d GPR ) was minimized. The standard deviation (SD) of the d GPR was evaluated for the optimized LM. RESULTS: It was confirmed that the coefficient q was larger for tighter tolerance. This result corresponds to the expectation that the attenuation of the a GPR u will be large for tighter tolerance. The p GPR and m GPR were observed to be proportional for all tolerances investigated. The SD of d GPR was 2.3, 4.1, and 6.7% for tolerances of 3%/3 mm, 3%/2 mm, 2%/2 mm, respectively. CONCLUSION: The DUP-based predicting method of the GPR was extended to 3D by introducing DUP attenuation and an optimized analytical LM to compensate for the low statistics of the learning data due to a finite number of detector elements. The precision of the predicted GPR is expected to be improved by improving the LM and by involving other metrics.