Differences between professionals in planning treatment for patients with stage III lung cancer using treatment-planning QA software

Reports of Practical Oncology and Radiotherapy


Hands-on seminar for image-guided adaptive brachytherapy and intracavitary/interstitial brachytherapy for uterine cervical cancer

Compared with the implementation speed of image-guided adaptive brachytherapy for uterine cervical cancer, that of intracavitary and interstitial brachytherapy is slow, possible because it requires more invasive procedure of inserting needles directly into tumours. To accelerate the implementation speed of intracavitary and interstitial brachytherapy, a first hands-on seminar for image-guided adaptive brachytherapy and intracavitary and interstitial brachytherapy for uterine cervical cancer was held on 26 November 2022, supported by Japanese Society for Radiology and Oncology. This article deals with this hands-on seminar and difference of degree of confidence of participants in starting intracavitary and interstitial brachytherapy before and after the seminar. The seminar consisted of lectures regarding intracavitary and interstitial brachytherapy in the morning and hands-on practice of needle insertion and contouring, as well as dose calculation practice using the radiation treatment system in the evening. Prior to and following the seminar, participants completed a questionnaire asking about their level of confidence in performing intracavitary and interstitial brachytherapy, expressed between 0 and 10 (the higher the number, the stronger the confidence). A total of 15 physicians, six medical physicists and eight radiation technologists from 11 institutions attended the meeting. The median level of confidence before and after the seminar was 3 (range, 0-6) and 5.5 (range, 3-7), respectively, and a statistically significant improvement was observed (P<0.001). It was suggested that the hands-on seminar on intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer improved the level of confidence of the attendees and propelled their motivation, through which it is expected that the implementation of intracavitary and interstitial brachytherapy will be accelerated.


Prostate-specific Antigen Levels Following Brachytherapy Impact Late Biochemical Recurrence in Japanese Patients With Localized Prostate Cancer.

PSA levels at 5 years post-treatment were associated with long-term recurrence of localized prostate cancer, which can help alleviate patient anxiety concerning prostate cancer recurrence if PSA levels remain low at 5 years after LDR-BT.


Extreme leanness, lower skeletal muscle quality, and loss of muscle mass during treatment are predictors of poor prognosis in cervical cancer treated with concurrent chemoradiation therapy

Human papillomavirus vaccination is not widespread in Japan, and the low screening rates result in many cases of locally advanced cervical cancer. We investigated the prognostic significance of sarcopenia in patients with cervical cancer to guide healthcare policies to improve treatment outcomes. This retrospective study included 83 patients with cervical cancer without distant metastasis who underwent primary concurrent chemoradiotherapy between 2013 and 2018. We analyzed the indicators of physical condition and muscle quantity using the SYNAPSE VINCENT software. Muscle mass and the relationship between treatment toxicity and prognosis were evaluated. The patients' median age was 60 (range 33-80) years. Cancer stage distribution was as follows: cT2b or higher, 84.3%; N1, 65.1%; and MA, 27.7%. The overall sarcopenia (skeletal muscle index [SMI] < 38.5) rate was 30.1%, and the rate was 33.9 and 22.2% in patients aged < 64 and ≥ 65 years, respectively. No correlation was observed between clinical stage and musculoskeletal indices. Treatment resulted in decreased body weight and SMI; after treatment, the sarcopenia rate increased to 37.3%. A higher intramuscular adipose tissue content (IMAC) reduced the number of chemotherapy cycles needed. Treatment-associated SMI decreases of ≥ 7% indicated poor prognosis, with significant differences in progression-free survival and overall survival (p = 0.013 and p = 0.012, respectively). Patients who were very lean (body mass index < 18.5 kg/m) before treatment had a poor prognosis (p = 0.016 and p < 0.001). Our findings emphasize the importance of assessing original nutritional status and maintaining muscle mass and quality during the treatment of patients with cervical cancer.

International Journal of Clinical Oncology


Effect of dental metal artifact conversion volume on dose distribution in head-and-neck volumetric-modulated arc therapy

Purpose: During treatment planning for head-and-neck volumetric-modulated arc therapy (VMAT), manual contouring of the metal artifact area of artificial teeth is done, and the area is replaced with water computed tomography (CT) values for dose calculation. This contouring of the metal artifact areas, which is performed manually, is subject to human variability. The purpose of this study is to evaluate and analyze the effect of inter-observer variation on dose distribution.Methods: The subjects were 25 cases of cancer of the oropharynx for which VMAT was performed. Six radiation oncologists (ROs) performed metal artifact contouring for all of the cases. Gross tumor volume, clinical target volume, planning target volume (PTV), and oral cavity were evaluated. The contouring of the six ROs was divided into two groups, small and large groups. A reference RO was determined for each group and the dose distribution was compared with those of the other radiation oncologists by gamma analysis (GA).As an additional experiment, we changed the contouring of each dental metal artifact area, creating enlarged contours (L), reduced contours (S), and undrawn contours (N) based on the contouring by the six ROs and compared these structure-sets.Results: The evaluation of inter-observer variation showed no significant difference between the large and small groups, and the GA pass rate was 100%. Similar results were obtained comparing structure-sets L and S, but in the comparison of structure-sets L and N, there were cases with pass rates below 70%.Conclusions: The results show that the artificial variability of manual artificial tooth metal artifact contouring has little effect on the dose distribution of VMAT. However, it should be noted that the dose distribution may change depending on the contouring method in cases where the overlap between PTV and metal artifact areas is large.

Journal of Applied Clinical Medical Physics


Clinical outcomes and prognostic factors of definitive radiotherapy for esophageal cancer

Purpose To assess the treatment results of definitive radiotherapy for esophageal cancer at Tokushima University Hospital and clarify the prognostic factors. Methods Seventy consecutive patients with esophageal cancer who underwent definitive radiotherapy between May 2004 and March 2012 were included in the present study. Local control rate, overall survival rate, and radiation morbidity were examined and univariate and multivariate analyses were performed to investigate prognostic factors. Results The 5-yearoverall survival rates of stages I, II, III, and IVA were 81%, 71%, 0%, and 9%, respectively. Performance status, clinical stage, and neoadjuvant chemotherapy were significant prognostic factors. A past history of interstitial pneumonia was associated with severe radiation-induced lung injury. Conclusions Patients who underwent definitive chemoradiotherapy for esophageal cancer in stage I/II showed good prognosis. However, treatment results of the patients in stage III/IV were not satisfactory, and those who could not undergo surgery after neoadjuvant chemotherapy had the worst prognosis.J.Med.Invest.66:99-105, February, 2019.

The Journal of Medical Investigation : JMI


Clinical outcomes of hypofractionated image-guided multifocal irradiation using volumetric-modulated arc therapy for brain metastases.

Volumetric-modulated arc therapy (VMAT) can be used to design hypofractionated radiotherapy treatment plans for multiple brain metastases. The purpose of this study was to evaluate treatment outcomes of hypofractionated image-guided multifocal irradiation using VMAT (HFIGMI-VMAT) for brain metastases. From July 2012 to December 2016, 67 consecutive patients with 601 brain metastases were treated with HFIGMI-VMAT at our institution. The prescribed dose was 50 Gy to a 95% volume of the planning target volume in 10 fractions. Fifty-five of the 67 patients had non-small-cell lung cancer, and the remaining 12 had other types of cancer. The median number of brain metastases was five, and the median maximum diameter was 1.2 cm. The median duration of follow-up was 12.0 months (range, 1.9-44.8 months), and the median survival time 18.7 months. Four patients with six lesions had local recurrences. The local control rate in the 64 assessed patients was 98.4% and 95.3% at 6 and 12 months, respectively (three died before assessment). The local control rate for the 572 assessed lesions was 99.8% and 99.3% at 6 and 12 months, respectively. Thirty-nine patients developed distant brain metastases, the distant brain control rate being 59.7% and 40.5% at 6 and 12 months, respectively. Acute toxicities were generally mild (Grade 1-2). Three patients (4.5%) developed radiation necrosis requiring corticosteroid therapy. The HFIGMI-VMAT technique with flat dose delivery was well tolerated and achieved excellent local control. This technique is a promising treatment option for patients with multiple and large brain metastases.


Predictive Factors for Prolonged Urination Disorder After Permanent 125I Brachytherapy for Localized Prostate Cancer

We assessed the change in LUTS after prostate brachytherapy to reveal factors for prolonged urination disorder. Four hundred and four patients received prostate brachytherapy at our institution and were followed-up for at least 2 years. We evaluated the correlation of mean IPSS changes and clinical factors. Using multivariate analysis, we also evaluated clinical factors with potential to delay IPSS resolution. In cases with prostate volume more than 30 cm, radiation dose to 90% of prostate volume (D90) more than 160 Gy, and radiation dose to 30% of the urethral volume (UD30) more than 240 Gy, mean IPSS levels were significantly higher, even 30 months after treatment. On multivariate analysis, baseline IPSS more than 8 points and D90 more than 160 Gy were significant predictors for delayed IPSS resolution. Our data suggest that higher baseline IPSS and higher D90 were predictors for prolonged urination disorder.


Effectiveness of Newly Developed Water-Equivalent Mouthpiece during External Beam Radiotherapy for Oral Cancer


Clinical Significance of Neoadjuvant Combined Androgen Blockade for More Than Six Months in Patients with Localized Prostate Cancer Treated with Prostate Brachytherapy.

The aim of this study is to clarify the clinical significance of neoadjuvant combined androgen blockade (CAB) for ≥ 6 months in patients with localized prostate cancer. A total of 431 patients with localized prostate cancer who underwent prostate brachytherapy (BT) with or without neoadjuvant CAB for ≥ 6 months with mean follow-up time of 64.6 months (range 24-108 months) were evaluated retrospectively. Of those 431, 232 patients received BT in combination with neoadjuvant CAB for ≥ 6 months. Biochemical recurrence-free rates (BRFRs) in 364 patients with at least 3 years of follow-up were evaluated by log-rank test. BRFR in patients with low-, intermediate- and high-risk prostate cancer were 98.1, 94.2 and 89.1%, respectively. In patients with intermediate-risk prostate cancer only, neoadjuvant CAB was significantly associated with BRFR (p = 0.0468). Especially in patients with intermediate-risk prostate cancer with radiation dose received by 90% of the prostate (D90) < 180 Gy, neoadjuvant CAB exerted a favorable impact on BRFR (p = 0.0429). On multivariate analyses, neoadjuvant CAB and D90 were independent predictors of BRFR (p = 0.0061 and p < 0.0001, respectively). Neoadjuvant CAB for ≥ 6 months has a favorable impact on BRFR in patients with intermediate-risk prostate cancer, particularly in patients with relatively low radiation doses of D90.


Changes of tumor and normal structures of the neck during radiation therapy for head and neck cancer requires adaptive strategy.

The treatment period over which radiation therapy is administered extends over several weeks. Since tumor shrinkage in response to radiation therapy and weight loss due to radiation-induced mucositis may impact on the dose distribution in both target and organ at risk in patients with head and neck cancer, the anatomical changes of tumor and neck volumes during this period should be taken into consideration. We investigated the anatomical changes that occurred in the target and normal structure of the neck during radiation therapy for pharyngeal cancer, and evaluated the necessity of an adaptive strategy. Ten patients with pharyngeal cancer who underwent radical chemoradiation therapy using 3-dimensional conformal radiation therapy RT (66-70 Gy in 33-35 fractions) between April 2009 and September 2010 were enrolled in the study. Patients underwent CT scans every week during their course of treatment. We analyzed the CT data in the radiation treatment planning system and measured changes of tumor, organ at risk, and neck volume. Gross tumor volume (GTV) was rapidly reduced by 28% of the original volume on average in the first 3 weeks. The right and left submandibular glands volume decreased to 70% and 63% of their initial volumes on average, respectively. The volume of the neck in the radiation fields decreased to 89% of its initial volume on average by the sixth week mainly caused by body weight loss due to acute radiation morbidity. Considerable anatomical change in the radiation filed that will affect dose distribution of the target and organ at risk was observed during radiation therapy for head and neck cancer.


High-dose-rate brachytherapy for patients with maxillary gingival carcinoma using a novel customized intraoral mold technique.

OBJECTIVE: The purpose of this study was to introduce a novel customized intraoral mold treatment for maxillary gingival carcinoma (UGC). STUDY DESIGN: Two patients with UGC were treated as salvage therapy using this technique. The mold was designed to keep normal soft tissues adjacent to the tumor away from the radioactive source as much as possible, and it was shielded by lead. The radiation dose on the buccal mucosa and tongue was measured at the inner and outer surfaces of the intraoral mold before starting high-dose-rate brachytherapy by the remote afterloading system, and was reduced to almost one tenth. RESULTS: The patient had no recurrence and no severe adverse effects on the normal soft tissue adjacent to the tumor until the end of the follow-up period. CONCLUSION: High-dose-rate brachytherapy using the novel customized intraoral mold might be a treatment option of not only salvage therapy, but definitive therapy of UGC.

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics


Risk factors for radiation pneumonitis caused by whole breast irradiation following breast-conserving surgery.

We evaluated risk factors of radiation pneumonitis (RP) after whole breast irradiation following breast-conserving surgery. Four hundred and seventy-two cases underwent whole breast irradiation with tangential field following breast-conserving surgery in our hospital, between January 2005 and April 2007. Of these cases, we performed statistical analyses for 423 breasts of 413 patients, using a pulmonary dose-volume histogram. Patient characteristics, treatment regimens and irradiation methods were included as variables in the analyses on risk factors of RP. As a result, 89 breasts of 84 cases (21%) were diagnosed with RP. The version 3.0 of the NCI Common Terminology Criteria for Adverse Events was used to evaluate the grade of pneumonitis: 77 cases (18.2%) were diagnosed as Grade 1 RP, 10 cases (2.3%) as Grade 2, and 2 cases (0.5%) as Grade 3. Multivariate analysis indicated that the significant risk factors for RP were central lung distance (CLD) (>1.8 cm) and the short axis length of the radiation field. The incidence of radiation-induced bronchiolitis obliterans organizing pneumonia (BOOP) syndrome significantly correlated only with CLD. The lung volume within the radiation field was shown to be a significant risk factor for RP and radiation-induced BOOP syndrome.


Effective bladder preservation strategy with low-dose radiation therapy and concurrent intraarterial chemotherapy for muscle-invasive bladder cancer.

PURPOSE: The aim of this study was to evaluate retrospectively the toxicity and response, bladder preservation, and survival of patients with muscle-invasive bladder cancer treated with multimodality therapy consisting of low-dose radiation therapy (RT) and concurrent intraarterial chemotherapy (IACT). METHODS AND MATERIALS:. Between November 1999 and July 2005, a total of 27 consecutive, previously untreated patients with muscle-invasive bladder cancer underwent transurethral bladder tumor resection followed by concurrent low-dose RT and IACT. Patients who achieved a complete response (CR) were followed up closely without further therapy, and patients who did not achieve a CR underwent further treatment. RESULTS: Complete response was achieved in 22 of 27 patients (81%). Of these 22 patients, 7 developed recurrences, and 3 died of their disease. In five patients who did not achieve CR, one died from bone metastases. The 3-year overall survival rate was 81%, with a median follow-up time of 27 months; and 22 of 27 patients (81%) with a preserved bladder were tumor-free at the last follow-up. Three patients (11%) developed grade 3 acute hematological toxicity. CONCLUSION: Multimodality therapy consisting of low-dose RT and concurrent IACT for muscle-invasive bladder cancer can achieve survival rates similar to those in patients treated with radical cystectomy, with successful bladder preservation and minimal adverse effects.


Prognostic significance of HIF-2alpha expression on tumor infiltrating macrophages in patients with uterine cervical cancer undergoing radiotherapy.

Hypoxia-inducible factor (HIF)-2alpha, a basic helix-loop-helix (bHLH)-PAS protein, is the principal regulator of the hypoxic transcriptional response. An immunohistochemical study reported strong HIF-2alpha expression in the cytoplasm of tumor infiltrative macrophages (TIMs). Thus we assessed the expression of HIF-2alpha in human cervical cancer tissue before radiation therapy and its relationship to the clinical outcome. Seventy three patients with histologically proven primary advanced squamous cell carcinoma of the uterine cervix underwent radiotherapy in Tokushima University Hospital after biopsy specimens were taken. Among 73 specimens stained for HIF-2alpha, 53 (72.6%) exhibited HIF-2alpha immunoreactivity in the TIMs. In only 5 of 73 cases, HIF-2alpha immunoreactivity was observed in the nuclei of tumor cells. The HIF-2alpha positive cell count ratio in TIMs was associated with disease-free survival (DFS) with the worst DFS (p=0.024) being in cases in the group with a high positive cell count ratio. A high HIF-2alpha positive cell count ratio in TIMs increased the risk of local recurrence (p=0.0142). These findings might suggest that the ratio of the HIF-2alpha positive cell in TIMs may be a new predictive indicator for prognosis before radiation therapy for uterine cervical cancer.

The Journal of Medical Investigation : JMI


Radiation therapy for cervical cancer in the elderly

To evaluate the long-term results of radical radiation therapy (RT) for cervical cancer in elderly patients. We reviewed the clinical records of 727 patients with cervical cancer who underwent radical RT at the Tokushima University Hospital and compared the treatment results of three age groups: </=64 years (younger group [YG], 337 patients), 65-74 years (young-old group [YOG], 258 patients), and >/=75 years (older group [OG], 132 patients). At the last follow-up, 155 YG (46%), 77 YOG (30%), and 48 OG patients (36%) had died of cervical cancer; the median follow-up periods were 82, 87, and 68 months, respectively. The 5-/10-year disease-specific survival rates were 60%/52% in YG, 76%/68% in YOG, and 66%/57% in OG. Differences between OG and the other groups were not significant. The 5-/10-year disease-specific survival rate of YOG was significantly superior to that of YG (p<0.001). Clinical stage was the only significant prognostic variable (p<0.001). Late radiation morbidity of grades 2-4 in the bladder and/or rectum occurred in 22% of YG, 31% of YOG, and 8% of OG patients. RT was well tolerated in elderly patients, and age was not a significant prognostic factor. In the management of cervical cancer, advanced age is not a contraindication to radical RT.


The effect of oral contrast on large bowel activity in FDG-PET/CT.

The purpose of this study was to determine the effect of oral contrast on FDG uptake in the colon and to determine the normal distribution of FDG in the colon. Sixty patients (30 patients in no contrast group and 30 patients in the received contrast group) underwent FDG-PET/ CT scans. The pattern of FDG uptake was classified into 5 patterns (diffuse, segmental, single-nodular, multi-nodular, and other) in 5 segments (ascending, transverse, descending, and rectosigmoid colon). SUVs of the no oral contrast group were examined. The ratios of FDG uptake patterns were compared in the received contrast group and no contrast group to evaluate the effect of oral contast. The effect of attenuation correction on the uptake pattern was evaluated by comparison of the attenuation-corrected and non-attenuation-corrected PET images. In the no contrast group, there was no significant uptake in 72 segments (59%) and a diffuse pattern was seen in 29 segments (24%), most frequently in the ascending colon and descending colon. A segmental pattern was seen in 15 segments (13%), most frequently in the rectosigmoid colon. A single-nodular pattern was seen in 3 segments (3%) and multi-nodular pattern in 1 segment (1%). A nodular pattern was seen only in the ascending colon. SUVmax of the ascending colon and that of the rectosigmoid colon were significantly higher than those of the transverse and descending colon. The frequencies of diffuse, multi-nodular and 'other' patterns were significantly higher in the received contrast group than in no contrast group. There was no significant difference between the frequency of the segmental pattern or the single nodular pattern in the two groups. There was no significant difference between the uptake patterns with attenuation correction and those without attenuation correction in either the received contrast group or no contrast group. Normal FDG uptake in the large bowel may show various degrees and patterns of uptake among the colonic segments. Oral contrast agent can cause focal or diffuse increased FDG uptake, which may be induced not only by the high CT density of oral contrast but also by an accelerated physiologic reaction of the large bowel.


The relationship between standard uptake value (SUV) and Hounsfield Unit (HU) of oral contrast agent for FDG-PET/CT study.

The aim of this study was to examine the relationship between CT density (Hounsfield Unit, HU) and the degree of fluoro-deoxyglucose (FDG) uptake, demonstrated as standard uptake value (SUV). Twenty contiguous patients (9 males, 11 females, age range of 29-79) were performed FDG-PET/CT scan with 750ml of 5% iodine-based oral contrast agent. A region of interest (ROI) was placed manually on oral contrast in the lumen of stomach, small bowel and ascending colon, avoiding contamination of other structures, and the average SUV and average HU were determined. R square and p value were applied to evaluate the correlation. The correlation between SUV and HU in each separate location is not significant. When all regions are combined, p value is significant (<0.05), but R square is not significant. Oral contrast can be one factor that influences measured FDG, and it is possible it acts as an irritant that increases metabolism in the bowel wall, resulting in increased FDG uptake.


Comparison of washout rate between planar image and polar map image: 123I-BMIPP study.

Myocardial cells obtain 60-90% of their energy from free fatty acids under aerobic conditions. 123I-BMIPP can demonstrate fatty acid metabolism in the myocardium and is used to evaluate cardiac diseases. Forty-three patients underwent BMIPP imaging in the early (15 min) and delayed (4 hr) phase, and the washout rate was calculated. We evaluate the washout rate by two methods, the polar map method and the planar image method. The two methods showed close correlation (r=0.473).