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.

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.

Analyses of the local control of pulmonary Oligometastases after stereotactic body radiotherapy and the impact of local control on survival.

BACKGROUND: Successful local therapy for oligometastases may lead to longer survival. The purpose of this multicentre retrospective study was to investigate factors affecting the local control (LC) of pulmonary oligometastases treated by stereotactic body radiotherapy (SBRT) and to investigate the impact of LC on survival. METHODS: The inclusion criteria included 1 to 5 metastases, the primary lesion and other extrathoracic metastases were controlled before SBRT, and the biological effective dose (BED10) of the SBRT was 75 Gy or more. The Cox proportional hazards model was used for analyses. RESULTS: Data of 1378 patients with 1547 tumours from 68 institutions were analysed. The median follow-up period was 24.2 months. The one-year, 3-year and 5-year LC rates were 92.1, 81.3 and 78.6%, respectively, and the 1-year, 3-year and 5-year overall survival rates were 90.1, 60.3 and 45.5%, respectively. Multivariate analysis for LC showed that increased maximum tumour diameter (p = 0.011), type A dose calculation algorithm (p = 0.005), shorter overall treatment time of SBRT (p = 0.035) and colorectal primary origin (p < 0.001 excluding oesophagus origin) were significantly associated with a lower LC rate. In the survival analysis, local failure (p < 0.001), worse performance status (1 vs. 0, p = 0.013; 2-3 vs. 0, p < 0.001), oesophageal primary origin (vs. colorectal origin, p = 0.038), squamous cell carcinoma (vs. adenocarcinoma, p = 0.006) and increased maximum tumour diameter (p < 0.001) showed significant relationships with shorter survival. CONCLUSIONS: Several factors of oligometastases and SBRT affected LC. LC of pulmonary oligometastases by SBRT showed a significant survival benefit compared to patients with local failure.

Analyses of local control and survival after stereotactic body radiotherapy for pulmonary oligometastases from colorectal adenocarcinoma.

This study is a subset analysis of a retrospective multicenter study performed in Japan and its purpose was to investigate the effectiveness of stereotactic body radiotherapy (SBRT) for pulmonary oligometastases from colorectal cancer. Local control (LC), freedom from further metastases, relapse-free survival and overall survival (OS) after SBRT were retrospectively analyzed. The Kaplan-Meier method was used to estimate lifetime data and the log-rank test was performed as univariate analyses. The Cox proportional hazards model was applied in multivariate analyses. Data for 330 patients with 371 tumors were used for analyses. The median follow-up period was 25.0 months. The 3-year LC, freedom from further metastases, relapse-free survival and OS rates were 64.9, 34.9, 24.9 and 63.4%, respectively. The results of multivariate analyses showed that a higher LC rate was associated with no history of local therapy for oligometastases (P = 0.01), SBRT without concurrent chemotherapy (P < 0.01), type B calculation algorithm (P < 0.01) and higher biological effective radiation doses (≥115 Gy, P = 0.04). A longer OS was associated with no history of local therapy for oligometastases (P = 0.04), a more recent period of SBRT (2010-15, P = 0.02), tumor located in the upper or middle lobe (P < 0.01) and higher biological effective radiation doses (≥115 Gy, P = 0.01). In conclusion, OS after SBRT was good, but LC rate was relatively low. The use of high biological effective radiation doses can improve both LC and OS outcomes.

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.

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.

Pulmonary Oligometastases Treated by Stereotactic Body Radiation Therapy: A Nationwide Survey of 1,378 Patients.

AIM: This study was performed to confirm the superior overall survival (OS) after pulmonary oligo-recurrence compared to pulmonary sync-oligometastases in a large nationwide study. PATIENTS AND METHODS: Patients that met the following criteria were included: 1 to 5 lung-only metastases at the beginning of stereotactic body radiation therapy (SBRT) was performed between January 2004 and June 2015, and the biological effective dose (BED) of SBRT was 75 Gy or more. The parameters included in the analyses were age, gender, ECOG PS, primary lesion, pathology, oligoetastatic state, SBRT date, chemotherapy before SBRT, chemotherapy concurrent SBRT, chemotherapy after SBRT, maximum tumor diameter, number of metastases, field coplanarity, dose prescription, BED10, OTT of SBRT. RESULTS: In total, 1,378 patients with 1,547 tumors were enrolled. Oligo-recurrence occurred in 1,016 patients, sync-oligometastases in 118, and unclassified oligometastases in 121. The three-year OS was 64.0% for oligo-recurrence and 47.5% for sync-oligometastasis (p<0.001). In the multivariate analysis, the hazard ratio (HR) for sync-oligometastases versus oligo-recurrence was 1.601 (p=0.014). Adverse events of Grade 5 were occurred in 3 patients. CONCLUSION: This is the first nationwide to indicate that the OS of patients with pulmonary oligo-recurrence is better than that of patients with sync-oligometastases.

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.

Reconsideration on Clinical Benefit of Pelvic Lymph Node Dissection during Radical Prostatectomy for Clinically Localized Prostate Cancer.

We conducted a review of the literature to identify the clinical benefits of pelvic lymph node dissection (PLND) during radical prostatectomy for clinically localized prostate cancer. The most recent guidelines recommend PLND, particularly extended PLND, during radical prostatectomy for localized prostate cancer. PLND is undoubtedly the most accurate method for nodal staging, and most patients, particularly those with high-risk cancer, are likely to undergo PLND during radical prostatectomy. Although many retrospective studies have assessed oncologic outcomes after PLND, its therapeutic benefit remains controversial. Patients with positive node(s) often have other more common unfavorable prognostic factors, such as seminal vesicle invasion, extra-prostatic extension, and positive surgical margins. Oncologic outcomes in patients who have not undergone PLND and those who have undergone PLND are almost identical. If an effective standard adjuvant therapy after prostatectomy is defined, the nodal status may be important and valuable. However, adjuvant treatment strategies for patients with a positive node have not been identified thus far. Therefore, determining the nodal status at surgery may not provide therapeutic benefit. PLND requires additional surgical time and is associated with several complications. Therefore, the indication for PLND should be considered carefully until well-designed prospective randomized trials establish high-quality clinical evidence.

Predictive gamma passing rate by dose uncertainty potential accumulation model.

PURPOSE: Intensity-modulated radiation therapy (IMRT) utilizes many small fields for producing a uniform dose distribution. Therefore, there are many field junctions in the target region, and resulting dose uncertainties are accumulated. However, such accumulation of the dose uncertainty has not been implemented in the current practice of IMRT dose verification. The purpose of this study is to develop a method to predict the gamma passing rate (GPR) using a dose uncertainty accumulation model. METHODS: Thirty-three intensity-modulated (IM) beams for head-and-neck cases with step-and-shoot techniques were used in this study. The treatment plan was created using the XiO treatment planning system (TPS). The IM beam was produced by the ONCOR Impression Plus linear accelerator. MapCHECK was used to measure the dose distribution. The distribution of a dose uncertainty potential (DUP) was generated by in-house software that accumulated field shapes weighted by a segmental monitor unit, followed by Gaussian folding. The width of the Gaussian was determined from the width of the lateral penumbra. The dose difference between the calculated and measured doses was compared with the estimated DUP at each point. The GPR of each beam was predicted for 2%/2-mm, 3%/2-mm, and 3%/3-mm tolerances by its own DUP histogram and a GPR-vs-DUP correlation of other beams using the leave-one-out cross-validation method. The predicted GPR was compared with the measured GPR to evaluate the performance of this prediction method. The criteria for the predicted GPR corresponding to a measured GPR ≥ 90% were estimated to examine the feasibility of estimating the measured GPR by this GPR prediction method. RESULTS: The DUP was confirmed to have proportionality to the standard deviation (SD) of the dose difference. The SDs of the difference between the measured and predicted GPRs were 3.1, 1.7, and 1.4% for 2%/2-mm, 3%/2-mm, and 3%/3-mm tolerances, respectively. The criteria of the predicted GPR corresponding to the measured GPR ≥ 90% were 94.1 and 95.0% with confidence levels of 99 and 99.9%, respectively. CONCLUSION: In this study, we confirmed the good proportionality between the dose difference and the estimated DUP. The results showed a feasibility to predict the dose difference from DUP as estimated by a DUP accumulation model. The predicted GPR developed in this study showed good accuracy for planar dose distributions of head and neck IMRT. The prediction method developed in this study is considered to be feasible as a substitute for the current practice of measurement-based verification of the dose distribution with gamma analysis.

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.

Salvage radiotherapy for second oligo-recurrence in patients with breast cancer.

A new concept designated 'oligo-recurrence (OR)' has been proposed, which indicates one to several distant metastases/recurrences in one or more organs, which can be treated with local therapy, after the primary site of the cancer has been controlled. The purpose of this study was to assess the efficacy and toxicity of salvage radiotherapy (RT) for the second OR of breast cancer. The second OR was defined as once-salvaged patients with OR who had a second failure that was also detected as the state of OR. Twenty-one patients with second OR were treated with salvage RT and were retrospectively analyzed. The sites of the second OR were locoregional recurrence in 7 patients and distant metastasis in 14 patients. Salvage RT was performed at a median total dose of 60 Gy. Nineteen (90%) patients had an objective response. The median overall survival and progression-free survival (PFS) times were 41 and 24 months after salvage RT for the second OR, respectively. The 3-year local (in-field) control (LC) rates were 93%. The toxicities were mild; acute toxicities ≥Grade 3 were seen in one patient with Grade 3 dermatitis, and no late toxicity ≥Grade 2 was observed. In conclusion, salvage RT for the second OR was able to achieve a better LC rate and longer PFS time without inducing severe toxicity, and therefore may be a potentially effective modality for inducing long-term survival in select patients.

Salvage Radiotherapy for Solitary Metachronous Bone Metastasis in Patients with Breast Cancer.

AIM: We assessed the efficacy and toxicity of salvage radiotherapy for solitary metachronous bone metastasis (SMBM) in patients with breast cancer. PATIENTS AND METHODS: We retrospectively analyzed 17 patients with SMBM who were treated with salvage radiotherapy. First failure was detected as SMBM in all patients. Salvage radiotherapy using three-dimensional treatment planning was performed at a median total dose of 50 Gy. Median daily dose was 2.0 Gy. RESULTS: Median follow-up was 40 months. Local recurrence of SMBM was noted in only two patients. The 3-year overall survival, progression-free survival, and local control rates were 93%, 51%, and 85%, respectively. Median overall and progression-free survival were 74 and 30 months, respectively. Toxicities were mild, and bone fractures were not observed. CONCLUSION: Salvage radiotherapy for SMBM was able to achieve higher local control rates without severe toxicity, as well as to provide longer progression-free survival; therefore, this may be an effective modality.

Radiotherapy using IMRT boosts after hyperbaric oxygen therapy with chemotherapy for glioblastoma.

The purpose of this study was to evaluate the feasibility and efficacy of radiotherapy (RT) using intensity-modulated radiotherapy (IMRT) boosts after hyperbaric oxygen (HBO) therapy with chemotherapy in patients with glioblastoma. Twenty-four patients with glioblastoma were treated with the combined therapy, which was RT using IMRT boosts after HBO with chemotherapy, and were retrospectively analyzed. The RT protocol was as follows: first, 3D conformal RT [40 Gy/20 fractions (fr)] was delivered to the gross tumor volume (GTV) and the surrounding edema, including an additional 1.5-2.0 cm. The IMRT boost doses were then continuously delivered to the GTV plus 5 mm (28 Gy/8 fr) and the surrounding edema (16 Gy/8 fr). Each IMRT boost session was performed immediately after HBO to achieve radiosensitization. The planned RT dose was completed in all patients, while HBO therapy was terminated in one patient (4%) due to Grade 2 aural pain. The toxicities were mild, no non-hematological toxicity of Grade 3-5 was observed. The 2-year overall survival (OS) and progression-free survival rates in all patients were 46.5% and 35.4%, respectively. The median OS time was 22.1 months. In conclusion, the combined therapy of RT using IMRT boosts after HBO with chemotherapy was a feasible and promising treatment modality for patients with glioblastoma. The results justify further evaluation to clarify the benefits of this therapy.

Concurrent hyperfractionated chemoradiotherapy for head and neck squamous cell carcinoma: the prognostic impact of the overall treatment time and completion rates of chemotherapy.

The purpose of this study was to investigate whether the overall treatment time and completion rates of chemotherapy were predictive factors for the survival rates in patients with squamous cell carcinoma of the head and neck (SCCHN) who were treated with concurrent chemoradiotherapy (CCRT) using hyperfractionated radiotherapy (RT) and daily carboplatin. The number of intermission days of RT were as follows; 0 (n = 37), 1-5 (n = 8), 6-10 (n = 12) and ≥11 (n = 12), and the days of RT without carboplatin; 0 (n = 27), 1-5 (n = 13), 6-10 (n = 13) and ≥7 (n = 16). The overall treatment time (≤48 vs ≥49 days) was a significant prognostic factor for the local control, disease-free survival and overall survival rates. The completion rate of chemotherapy, as the number of days of RT without carboplatin, was not a significant factor affecting any of the survival rates. In discussion, the strengths of the present study contain that all the patients were treated with 72 Gy delivered as 1.2 Gy twice daily, and received concurrent chemotherapy comprising daily carboplatin as a radio-sensitizer. Based on the results, the completion rate of chemotherapy may have a lower impact on the local control rate in comparison with the overall treatment time. We believe that when a treatment interruption is needed because of the acute toxicities, hyperfractionated RT should be resumed as soon as possible independently while continuing the break of daily carboplatin. The overall treatment time influenced the clinical outcomes in SCCHN patients treated with hyperfractionated CCRT using carboplatin, while the impact of the completion rates of daily carboplatin was limited. Sixty-nine consecutive patients with SCCHN were initially treated with definitive CCRT and were retrospectively analyzed. All 69 patients were treated with CCRT using hyperfractionated RT of 72 Gy in 60 fractions and daily carboplatin (25 mg/m(2)). The patients treated with other chemotherapeutic regimens or induction chemotherapy were excluded. On the intermission days of the RT, carboplatin was not prescribed. After the intermission, CCRT using RT plus daily carboplatin or RT alone was resumed.

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.

Definitive 3D-CRT for clinically localized prostate cancer: modifications of the clinical target volume following a prostate MRI and the clinical benefits.

PURPOSE: To evaluate the modifications of the tumor stage and clinical target volume following a prostate magnetic resonance imaging (MRI) to evaluate the tumor (T) staging, and the clinical benefits for prostate cancer. METHODS: A total of 410 patients with newly diagnosed and clinically localized prostate cancer were retrospectively analyzed. The patients were treated with definitive three-dimensional conformal radiotherapy (3D-CRT). In all of the patients, digital rectal examination, transrectal ultrasound, prostate biopsy and computed tomography were performed to evaluate the clinical stage. Of the 410 patients, 189 patients had undergone a prostate MRI study to evaluate the T staging, and 221 patients had not. RESULTS: Modification of the T stage after the prostate MRI was seen in 39 (25%) of the 157 evaluable patients, and a modification of the risk group was made in 14 (9%) patients. Eventually, a modification of the CTV in 3D-CRT planning was made in 13 (8%) patients, and 10 of these had extracapsular disease. Most of the other modifications of the T staging were associated with intracapsular lesions of prostate cancer which did not change the CTV. There were no significant differences in the biological relapse-free survival between the patients with and without a prostate MRI study. CONCLUSIONS: Modification of the CTV were recognized in only 8% of the patients, most of whom had extracapsular disease, although that of the T stage was seen in approximately one-quarter of the patients. Prostate MRI should only be selected for patients with a high probability of extracapsular involvement.

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.

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.