Radiation Oncologists' Views on Adjuvant Radiotherapy for Early-Stage Breast Cancer in the Elderly: Comparisons between Japan and the United States.

PURPOSE: To understand perspective on breast cancer using a survey. MATERIALS & METHODS: Questionnaire was distributed to 304 Japanese radiation oncologists (RadOncs) (response rate: 64.1%). Result was compared with a similar US survey. RESULTS: In a scenario with an 81-year-old patient with comorbidities, while most US RadOncs chose to tell that radiation might not be necessary, 2% of Japanese chose it. In a scenario with a healthy 65-year-old breast cancer patient with lumpectomy, while most US RadOncs chose to discuss omission of radiation, 24.5% of Japanese chose it. CONCLUSIONS: Differences were observed on radiotherapy for older early-stage breast cancer.

Dosimetric investigation of whole-brain radiotherapy with helical intensity modulated radiation therapy and volumetric modulated arc therapy for scalp sparing.

Objective: Intensity-modulated radiotherapy (IMRT) is a well-established radiotherapy technique for delivering radiation to cancer with high conformity while sparing the surrounding normal tissue. Two main purposes of this study are: (1) to investigate dose calculation accuracy of helical IMRT (HIMRT) and volumetric-modulated arc therapy (VMAT) on surface region and (2) to evaluate the dosimetric efficacy of HIMRT and VMAT for scalp-sparing in whole brain radiotherapy (WBRT). Methods: First, using a radiochromic film and water-equivalent phantom with three types of boluses (1, 3, 5 mm), calculation/measurement dose agreement at the surface region in the VMAT and HIMRT plans were examined. Then, HIMRT, 6MV-VMAT and 10MV-VMAT with scalp-sparing, and two conventional three-dimensional conformal radiotherapy plans (6MV-3DCRT and 10MV-3DCRT; as reference data) were created for 30 patients with brain metastasis (30 Gy/10 fractions). The mean dose to the scalp and the scalp volume receiving 24 and 30 Gy were compared. Results: The percentage dose differences between the calculation and measurement were within 7%, except for the HIMRT plan at a depth of 1 mm. The averaged mean scalp doses [Gy], V24Gy [%], and V30Gy [%] (1SD) for 6MV-3DCRT, 10MV-3DCRT, HIMRT, 6MV-VMAT, and 10MV-VMAT were [26.6 (1.1), 86.4 (7.3), 13.2 (4.2)], [25.4 (1.0), 77.8 (7.5), 13.2 (4.2)], [23.2 (1.5), 42.8 (19.2), 0.2 (0.5)], [23.6 (1.6), 47.5 (17.9), 1.2 (1.8)], and [22.7 (1.7), 36.4 (17.6), 0.7 (1.1)], respectively. Conclusion: Regarding the dose parameters, HIMRT achieved a lower scalp dose compared with 6MV-VMAT. However, the highest ability to reduce the mean scalp dose was showed in 10MV-VMAT. Advances in knowledge: Scalp-sparing WBRT using HIMRT or VMAT may prevent radiation-induced alopecia in patients with BM.

Phase I/II prospective clinical trial for the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer.

OBJECTIVE: The purposes of this trial were to demonstrate the feasibility and effectiveness of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients in the phase I/II prospective clinical trial. METHODS: Patients with FIGO stage IB2-IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by magnetic resonance imaging were eligible for this clinical trial. The protocol therapy included 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of HBT and pelvic radiotherapy with a central shield up to 50-50.4 Gy in 25-28 fractions. The primary endpoint of phase II part was 2-year pelvic progression-free survival (PPFS) rate higher than historical control of 64%. RESULTS: Between October 2015 and October 2019, 73 patients were enrolled in the initial registration and 52 patients proceeded to the secondary registration. With the median follow-up period of 37.3 months (range, 13.9-52.9 months), the 2- PPFS was 80.7% (90% confidence interval [CI]=69.7%-88%). Because the lower range of 90% CI of 2-year PPFS was 69.7%, which was higher than the historical control ICBT data of 64%, therefore, the primary endpoint of this study was met. CONCLUSION: The effectiveness of HBT were demonstrated by a prospective clinical study. Because the dose goal determined in the protocol was lower than 85 Gy, there is room in improvement for local control. A higher dose might have been needed for tumors with poor responses.

Time to Pain Relapse After Palliative Radiotherapy for Bone Metastasis: A Prospective Multi-institutional Study.

BACKGROUND/AIM: Low risk asymptomatic bone metastasis (LRABM) without gross osteolytic changes tends to be out of indication for radiotherapy. The aim of this study was to evaluate the time between the end of palliative radiotherapy of bone metastasis (BM) until the start of new pain, in patients with painful BM. PATIENTS AND METHODS: Patients with BM were prospectively assessed for location and strength of pain every month for one year after radiotherapy. The correlation of pain relapse at irradiated site, and pain onset outside the irradiated site was evaluated with sex, age, primary tumor, pathology of tumor, visceral metastases, baseline scores for Eastern Cooperative Oncology Group performance status (PS), and baseline verbal rating scale (VRS). RESULTS: A hundred and thirty-two patients were included (79 males and 53 females). Median age was 66 years. Primary sites were lung (n=60), breast (n=17), colon (n=12), prostate (n=11), and others (n=33) (one patient had two primary sites). Median follow-up was 185 days. Pain relief was observed in 92 patients (86.0%). Out of them, pain progression was observed in 69.6%. Median time to pain progression was 75.5 days. Pain onset outside the irradiated site was observed in 57 patients (43.2%). Median time to pain onset was 109 days. Out of the 57 patients, 13 (22.8%) had LRABM which existed before the start of radiotherapy. There were 54 patients with LRABM in this study and because many patients had more than one LRABM, the total LRABM sites were 123. Out of them, pain onset was observed within one year after irradiation in 44 (36%) lesions. Median time to pain onset was 67 days, which was the shortest of the three: irradiated site, out of the irradiated site, and LRABM site. Risk factors for high probability of pain onset within one year in LRABM lesions were female sex (showing a trend in univariate analysis), and pelvic, skull and spine metastasis (significant in multivariate analysis). CONCLUSION: Time to pain onsets in LRABM are relatively short, especially in female patients with pelvic, skull and spine metastasis. In these patients, prophylactic radiotherapy could be an option to consider.

The effectiveness of moisturizer on acute radiation-induced dermatitis in breast cancer patients: a systematic review and meta-analysis.

PURPOSE: We conducted a systematic review and meta-analysis to investigate the effectiveness of moisturizers on acute radiation dermatitis (ARD) in breast cancer patients receiving radiotherapy (RT). METHODS: PubMed, the Cochrane Library, CINAHL, and Ichushi-Web were searched for randomized controlled trials (RCTs) from April 2015 to March 2020. Assessments included type of intervention, cohort, outcomes, and quality of evidence. To evaluate the effect of moisturizer on ARD, we restricted analyses to studies comparing with standard skin care or no treatment. Outcomes were ARD severity and skin-related QOL (quality of life). Eligible studies were identified, and risk ratios and mean differences were extracted to compare outcome data. RESULTS: We screened 210 RCTs along with 14 studies included in a previous iteration of this analysis (2016), supplemented by a hand search (n = 9). Finally, we included 6 RCTs that investigated the effectiveness of standard type moisturizers in breast cancer patients receiving RT. Evidence (weak certainty) suggests that moisturizer use might reduce ≥ grade 3 ARD. QOL assessed by Skindex-16 improved with moisturizer use. Pain and pruritus measured by the visual analog scale (VAS) resulted in a smaller and nonsignificant difference in favor of moisturizer use. However, the certainty of the evidence was very weak in QOL. CONCLUSIONS: The proactive use of moisturizer may play a role in reducing ARD and improving skin-related QOL, although the certainty of the evidence was weak to very weak. Future high-quality RCTs should be initiated to strengthen these results.

Strontium-89 chloride delivery for painful bone metastases in patients with a history of prior irradiation.

BACKGROUND: Re-irradiation of a previously irradiated site must be done with careful consideration to minimize dose to organs at risk. AIMS: To evaluate pain response and safety of Sr-89 administration for painful bone metastases after prior irradiation. METHODS: We retrospectively reviewed patients with Sr-89 injection for painful bone metastasis in a previously irradiated site. All patients were seen in follow-up at 1, 2, 3, and 4 months after injection and every 6 months thereafter. Pain control, toxicity, and pain progression-free survival were analyzed. Correlation of pain relapse with the following characteristics was analyzed: gender, age, primary tumor, tumor pathology, baseline performance status, and baseline verbal rating scale. RESULTS: Among 25 patients analyzed (10 male, 15 female), median age was 68 (range, 50-81) years. Primary tumor sites included lung (n = 11), breast (n = 3), uterine cervix (n = 3), prostate (n = 3), and others (n = 5). Median follow-up was 25 (range, 1-76) months. Pain relief was observed in 24 patients (96.0%). One- and 2-year pain progression-free survival rates in these patients were 54.5% and 48.4%, respectively. Median time to pain progression was 5 (range, 2-16) months. Statistically significantly lower pain progression-free survival was observed in patients with osteolytic bone metastases (p < 0.01). No grade 3 or worse adverse events were observed. CONCLUSION: Sr-89 injection showed pain relief in most of our patients with painful bone metastases in a previously irradiated site and caused no grade 3 or worse adverse events. Sr-89 is an option for patients with a painful bone metastasis in a previously irradiated site.

An Asian multi-national, multi-institutional, retrospective study on image-guided brachytherapy in cervical adenocarcinoma and adenosquamous carcinoma.

Purpose: There are limited reports on outcomes of three-dimensional image-guided brachytherapy (3D-IGBT) for cervical adenocarcinoma in Asia. In a multi-institutional retrospective study, we assessed the clinical outcomes of three-dimensional image-guided brachytherapy for cervical adenocarcinoma or adenosquamous carcinoma (CA/CAC) in Asian countries. Material and methods: Patients who had undergone definitive radiation therapy/concurrent chemoradiotherapy for untreated cervical cancer between 2000 and 2016 were registered. Those who had undergone 3D-IGBT for histologically proven CA/CAC were included. Data on patients' characteristics and treatment were collected, including tumor reduction rate (defined as a percentage of reduction in tumor size before brachytherapy compared with that at diagnosis) and high-risk clinical target volume D90. Overall survival (OS), local control (LC), and progression-free survival (PFS) rates were calculated using Kaplan-Meier method. Late toxicities were assessed using common terminology criteria for adverse events version 4.0. Results: Anonymized data of 498 patients were collected. Of the 498 patients, 36 patients met inclusion criteria. The median follow-up period was 39 months. The 3-year OS, LC, and PFS rates were 68.4%, 68.5%, and 44.4%, respectively. After treatment, five patients had tumor re-growth without complete disappearance of the tumor. Two patients developed grade 3 vaginal toxicity or grade 4 rectal toxicity; none developed other severe late toxicities. A tumor reduction rate of > 26.3% was the only significant factor in multivariate analyses, and was associated with significantly better OS (p = 0.018), LC (p = 0.022), and PFS (p = 0.013). There were no significant trends in local control or dose to high-risk clinical target volume D90. Conclusions: LC rate of CA/CAC was insufficient despite 3D-IGBT. Meanwhile, tumor reduction rate was associated with LC, OS, and PFS rates. Therefore, CA/CAC may require a different treatment strategy than that applied in cervical squamous cell carcinoma.

Large volume was associated with increased risk of acute non-hematologic adverse events in the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer: preliminary results of prospective phase I/II clinical trial.

OBJECTIVE: This is the preliminary results of a multi-center prospective clinical trial evaluating the feasibility of the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer. METHODS: Patients with FIGO stage IB2, IIA2, IIB, IIIA, IIIB and IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by MRI were eligible. Protocol therapy consisted of 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of hybrid of intracavitary and interstitial and pelvic radiotherapy with central shield up to 50-50.4 Gy in 25-28 fractions. The primary endpoint of phase I part was that the rate of grade ≥ 3 acute non-hematologic adverse events related to hybrid of intracavitary and interstitial would be <10%. RESULTS: Between October 2015 and October 2019, 74 patients underwent primary registration, with 52 patients eventually proceeding to the secondary registration. The median pretreatment tumor width was 5.7 cm, and FIGO Stages were IB2 10, IIA2 2, IIB 20 and IIIB 20, respectively. The median high-risk clinical target volume D90 was 72.0 Gy (54.8-86.6 Gy, EQD2), rectum D2cc was 53.7 Gy (29.3-80.3 Gy) and bladder D2cc was 69.8 Gy (38.9-84.8 Gy). The rate of grade ≥ 3 non-hematologic adverse events related to hybrid of intracavitary and interstitial was 1.9% (1/52), and 17.3% (9/52) of patients experienced non-hematologic adverse events related to hybrid of intracavitary and interstitial of any grade. In multivariate analysis, high-risk clinical target volume ≥ 35 ml was associated with an increased risk of any grade of acute non-hematologic adverse events related to hybrid of intracavitary and interstitial (P = 0.036). CONCLUSION: The feasibility and reproducibility of hybrid of intracavitary and interstitial were demonstrated from a multi-center prospective clinical trial.

An Asian multi-national multi-institutional retrospective study comparing intracavitary versus the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical carcinoma.

This study is an international multi-institutional retrospective study comparing the clinical outcomes between intracavitary brachytherapy (ICBT) and the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients treated with definitive radiation therapy. Locally advanced cervical cancer, the initial size of which is larger than 4 cm and treated by concurrent chemoradiotherapy and image-guided adaptive brachytherapy, were eligible for this retrospective study. Patients who received HBT at least once were included in the HBT group, and patients who received only ICBT were included in the ICBT group. Anonymized data from 469 patients from 13 institutions in Japan, one from Korea and one from Thailand, were analyzed. Two hundred eighty and 189 patients were included in the ICBT group and the HBT group, respectively. Patients in the HBT group had more advanced stage, non-Scc histopathology, a higher rate of uterine body involvement, larger tumor at diagnosis, larger tumor before brachytherapy and a lower tumor reduction ratio. With a median follow-up of 51.3 months (2.1-139.9 months), 4-y local control (LC), progression-free survival (PFS) and overall survival (OS) for the entire patient population were 88.2%, 64.2% and 83%, respectively. The HBT group received a higher HR-CTV D90 than that of the ICBT group (68.8 Gy vs 65.6 Gy, P = 0.001). In multivariate analysis, the non-Scc histological subtype, HR-CTV D95 ≤ 60 Gy, reduction ratio ≤ 29% and total treatment time (TTT) ≥ 9 weeks were identified as the independent adverse prognostic factors for LC. Regarding LC, no difference was found between ICBT and HBT (4-y LC 89.3% vs 86.8%, P = 0.314). After adjustment for confounding factors by propensity score matching, no advantage of applying HBT was demonstrated regarding LC, PFS, or OS. Despite the fact that HBT patients had more adverse clinical factors than ICBT patients, HBT delivered a higher dose to HR-CTV and resulted in comparable LC.

Workplace Gender Inequity Is Driven by Broader Societal Inequity: A Qualitative Study of Senior Japanese and American Radiation Oncologists.

PURPOSE: Gender inequity in medicine harms society, and often originates in the context of broader societal discrimination. This study explores the experiences of older women in the radiation oncology specialty in Japan and the United States, with an emphasis on understanding how broader gender inequity affects career trajectory. Radiation oncology is an ideal setting to investigate cross-cultural physician gender equity issues, because few women enter the field despite fewer barriers (eg, frequent emergencies, evening/weekend hours, long procedures) that are commonly cited by women as deterrents in specialty selection. METHODS AND MATERIALS: Between 2012 and 2016, the authors interviewed 14 older women in radiation oncology (department chairs or full professors), with 6 from Japan and 8 from the United States. Multiple analysts identified themes to explore the impact of societal gender inequity on female radiation oncologists' careers. RESULTS: Five themes were identified: (1) childhood gender constructs affect career aspirations, (2) persistent sexism and gender-based workplace challenges affect women's careers, (3) gender inequity in the home affects women's careers, (4) non-gender-related factors intersect to affect women's career satisfaction, and (5) attaining gender equity appears to be even more challenging in Japan compared with the United States. CONCLUSIONS: Female radiation oncologists in 2 of the most technologically advanced countries report that gender discrimination across their lifespans substantially affects career success. Because gender inequality reflects societal injustice and negatively affects scientific progress and patient outcomes, future research should focus on global approaches to address professional and domestic gender constructs that impede women's career progress.

Clinical value of serum biomarkers, squamous cell carcinoma antigen and apolipoprotein C-II in follow-up of patients with locally advanced cervical squamous cell carcinoma treated with radiation: A multicenter prospective cohort study.

There are currently no reliable, established serum biomarkers to predict the prognosis of radiotherapy for advanced cervical cancer. We aimed to identify serum biomarkers for survival after radiotherapy for cervical cancer. In this multicenter prospective cohort study, the usefulness of pre- and posttreatment serum protein levels of potential biomarkers, including squamous cell carcinoma antigen (SCC-Ag), apolipoprotein C-II (ApoC-II), matrix metalloproteinase (MMP)1, and MMP2, were evaluated together with clinical factors in 145 cervical cancer patients in order to determine their suitability to predict survival. Progression-free survival (PFS) was the primary endpoint, and overall survival (OS), pelvic PFS (PPFS), and distant metastasis-free survival (DMFS) were the secondary endpoints. Blood samples were collected before and 1 month after radiotherapy to measure serum biomarker levels. ApoC-II was measured using a monoclonal antibody-based enzyme-linked immunosorbent assay, which was developed for this purpose. Kaplan-Meier method, log-rank test, and univariate and multivariate Cox proportional hazards models were used for statistical analyses. In multivariate analysis, larger tumor size was independently associated with shorter PFS, OS, PPFS, and DMFS, while longer overall treatment time was independently associated with shorter PPFS. Higher pretreatment SCC-Ag (P < 0.001) was associated with shorter DMFS. Higher posttreatment SCC-Ag (P = 0.017) was also associated with shorter DMFS. Pretreatment ApoC-II was associated with PPFS in univariate analysis (P = 0.048), but not in multivariate analysis. Patients with pretreatment ApoC-II levels ≤ 25.8 µg/ml had shorter PPFS than those with pretreatment ApoC-II levels > 25.8 µg/ml (P = 0.023, log-rank test). Pre- and posttreatment serum SCC-Ag and pretreatment serum ApoC-II levels may be important biomarkers to predict survival outcomes of patients with cervical cancer after radiotherapy. Pre- and posttreatment SCC-Ag and pretreatment ApoC-II might be useful in clinical settings for screening patients to improve treatment strategies in cervical cancer.

Why not de-intensification for uterine cervical cancer?

OBJECTIVE: The majority of uterine cervical cancer is known to be related to human papillomavirus (HPV), and HPV-related tumors are known to be radio-sensitive. In the management of HPV-related oropharyngeal cancer, de-intensification of treatment has been attempted; however, no such attempt is performed in the management of cervical cancer. The aim of this study was to identify a group of patients who can safely be treated by de-escalated treatment intensity. METHODS: From the Asian international multi-institutional retrospective study involving 13 Japanese, one Thailand, and one Korean institutions based on 469 patients, squamous cell carcinoma (Scc), tumor reduction ratio ≥29%, tumor size before brachytherapy ≤4 cm, and total treatment time (TTT) <9 weeks were identified as factors having an influence on local control. Based on these findings, low-risk patients having these four factors were extracted, and treatment outcomes categorized in 10 Gy increment of CTVHR D90 were compared. RESULTS: Among 469 patients, 162 patients (34.5%) met the criteria of low-risk group, and 63, 41, 43, and 15 patients were categorized in CTVHR D90 50-60 Gy, 60-70 Gy, 70-80 Gy, and >80 Gy, respectively. While 4-y progression-free survival ranged from 66 to 80%, 4-y local control was consistently over 90% in every dose group. Rectum and bladder D2cc and incidence of late adverse events decreased as CTVHR D90 decreased. CONCLUSIONS: The low-risk patients achieved favorable local control with CTVHR D90 <80 Gy. A personalized treatment strategy based on tumor response could also be adopted for cervical cancer.

Radiosensitization using hydrogen peroxide in patients with cervical cancer.

The purpose of the present study was to analyze the feasibility and safety of radiosensitization using hydrogen peroxide for cervical cancer. In superficial tumors, breast cancer and hepatocellular carcinoma, the safety and effectiveness of radiosensitization has been reported; to the best of our knowledge, however, there are no reports on cervical cancer. A total of 20 patients with cervical cancer were recruited. Inclusion criteria were as follows: Patients who required radical external beam radiotherapy (RT); ineligible for or refused brachytherapy; age, ≥20 years; no hematogenous metastasis; Eastern Cooperative Oncology Group Performance Status up to 2; and had not undergone prior treatment. Hydrogen peroxide was used twice a week in combination with RT. A 3% hydrogen peroxide solution-soaked gauze was inserted into the vagina during RT. A total of 45 Gy was delivered in 25 fractions to the whole pelvis with a boost of 10 Gy in 5 fractions if pelvic or para-aortic metastatic lymph nodes were observed. Ultimately, 18 patients were evaluated. Among the 17 patients (excluding one patient with tumor in situ), the one- and two-year overall survival rates were both 90% in patients with stage I/II and 86% in stage III/IV cervical cancer. The adverse events were well tolerated with no severe acute or late adverse events. Although limited by small sample size, short observation time and low radiation dose, the present study demonstrated that radiosensitization treatment may be an option for patients who cannot undergo brachytherapy. The study was retrospectively registered at the university hospital medical information network center (no. UMIN000039045) on January 6, 2020.

Results of a nationwide survey on Japanese clinical practice in breast-conserving radiotherapy for breast cancer.

The Breast Cancer Group of the Japanese Radiation Oncology Study Group conducted a nationwide questionnaire survey on the clinical practice of postoperative radiotherapy for breast-conserving treatment for breast cancer. This questionnaire consisted of 18 questions pertaining to the annual number of treated patients, planning method, contouring structure, field design, dose-fractionated regimen, application of hypofractionated radiotherapy, boost irradiation, radiotherapy for synchronously bilateral breast cancer, and accelerated partial breast irradiation. The web-based questionnaire had responses from 293 Japanese hospitals. The results indicated the following: treatment planning is performed using relatively similar field designs and delivery methods; the field-in-field technique is used at more than one-third of institutes; the commonest criteria for boost irradiation is based on the surgical margin width (≤5 mm) and the second commonest criteria was age (≤40 or ≤50 years), although some facilities applied a different age criterion (>70 years) for omitting a tumor bed boost; for conventional fractionation, almost all institutes delivered 50 Gy in 25 fractions to the conserved whole breast and 10 Gy in 5 fractions to the tumor bed. This survey revealed that 43% of hospitals offered hypofractionated radiotherapy, and the most common regimens were 42.56 Gy in 16 fractions for whole-breast irradiation and 10.64 Gy in 4 fractions for boost irradiation. Almost all of the facilities irradiated both breasts simultaneously for synchronously bilateral breast cancer, and accelerated partial breast irradiation was rarely offered in Japan. This survey provided an overview of the current clinical practice of radiotherapy for breast-conserving treatment of breast cancer in Japan.

Limited Impact of Setup and Range Uncertainties, Breathing Motion, and Interplay Effects in Robustly Optimized Intensity Modulated Proton Therapy for Stage III Non-small Cell Lung Cancer.

PURPOSE: To investigate the impact of setup and range uncertainties, breathing motion, and interplay effects using scanning pencil beams in robustly optimized intensity modulated proton therapy (IMPT) for stage III non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Three-field IMPT plans were created using a minimax robust optimization technique for 10 NSCLC patients. The plans accounted for 5- or 7-mm setup errors with ±3% range uncertainties. The robustness of the IMPT nominal plans was evaluated considering (1) isotropic 5-mm setup errors with ±3% range uncertainties; (2) breathing motion; (3) interplay effects; and (4) a combination of items 1 and 2. The plans were calculated using 4-dimensional and average intensity projection computed tomography images. The target coverage (TC, volume receiving 95% of prescribed dose) and homogeneity index (D2 - D98, where D2 and D98 are the least doses received by 2% and 98% of the volume) for the internal clinical target volume, and dose indexes for lung, esophagus, heart and spinal cord were compared with that of clinical volumetric modulated arc therapy plans. RESULTS: The TC and homogeneity index for all plans were within clinical limits when considering the breathing motion and interplay effects independently. The setup and range uncertainties had a larger effect when considering their combined effect. The TC decreased to <98% (clinical threshold) in 3 of 10 patients for robust 5-mm evaluations. However, the TC remained >98% for robust 7-mm evaluations for all patients. The organ at risk dose parameters did not significantly vary between the respective robust 5-mm and robust 7-mm evaluations for the 4 error types. Compared with the volumetric modulated arc therapy plans, the IMPT plans showed better target homogeneity and mean lung and heart dose parameters reduced by about 40% and 60%, respectively. CONCLUSIONS: In robustly optimized IMPT for stage III NSCLC, the setup and range uncertainties, breathing motion, and interplay effects have limited impact on target coverage, dose homogeneity, and organ-at-risk dose parameters.

Satisfaction of breast cancer patients regarding surgery and radiation therapy: A survey in Japan.

PURPOSE: To evaluate patient satisfaction in Japan and factors, including timing factors, cost, and specific medical practices derived from Western influence (shared decision-making and second opinion), which might affect satisfaction. METHODS AND MATERIALS: All patients who presented to 1 large Japanese department of radiation oncology for postoperative radiation therapy for breast cancer from September 2010 to November 2013 were included in this study. The questionnaire was distributed to patients after the radiation oncologist consultation, and patients were asked to complete it anonymously by the end of treatment. We measured patient satisfaction with overall treatment and for each treatment separately (surgery, radiation oncology). We further inquired regarding facts that could affect satisfaction, including time from diagnosis to treatment start, waiting time in waiting room for consultation, average length of consultations, out-of-pocket cost for breast cancer treatment, patients' opinion of the cost, level of inclusion of the patient in decision-making, level of the patient sharing her feelings with her physician, and whether the patients had asked for second opinion. RESULTS: Of 364 patients surveyed, 214 (58.5%) responded. Overall satisfaction and satisfaction with surgeon and with radiation oncologist were 95.7%, 98.5%, and 98.2%, respectively. Factors correlated with satisfaction were waiting time for the consult in the waiting room, treatment cost, and perceived degree of sharing feelings with physicians. Overall, 27 patients (12.6%) reported having asked for second opinions. Of those who did not seek a second opinion, most (173) indicated that they did not think it was necessary. CONCLUSIONS: In a large, typical Japanese radiation oncology practice, breast cancer patients' satisfaction correlated with waiting time, cost, and the rate with which the patient shared her feelings with her physician. This illuminates targets for quality improvement within the Japanese system and provides interesting cross-cultural comparative data for other countries in which the context of care may differ.

Effects of Electrostimulation with Blood Flow Restriction on Muscle Size and Strength.

PURPOSE: Low-load voluntary exercise can induce muscle hypertrophy and strength gain in working muscles when combined with blood flow restriction (BFR). However, it is unknown whether such hypertrophy and strength gain can be induced by involuntary muscle contractions triggered via low-intensity neuromuscular electrical stimulation (NMES) combined with BFR. The purpose of this article was to investigate whether low-intensity NMES combined with BFR (NMES-BFR) could elicit muscle hypertrophy and strength gain in the quadriceps. METHODS: Eight untrained young male participants (mean ± SE; age, 26.2 ± 0.7 yr; height, 1.74 ± 0.02 m; body weight, 71.4 ± 4.8 kg) were subjected to 23 min of unilateral low-intensity (5%-10% of maximal voluntary contraction) NMES twice per day (5 d·wk⁻¹) for 2 wk: one leg received NMES-BFR and the other leg received NMES alone. Quadriceps muscle thickness and isometric and isokinetic strength were measured before and every week throughout the training and detraining periods. RESULTS: In NMES-BFR legs, muscle thickness increased after 2 wk of training (+3.9%) and decreased after 2 wk of detraining (-3.0%). NMES-BFR training also increased maximal knee extension strength in isometric (+14.2%) and isokinetic (+7.0% at 90°·s⁻¹ and +8.3% at 180°·s⁻¹) voluntary contractions. In addition, maximal isometric strength decreased (-6.8%), whereas no large fall (-1.9% at 90°·s⁻¹ and -0.6% at 180°·s⁻¹) in isokinetic maximal strength was evident after 2 wk of detraining. In legs that received NMES alone, no prominent change was observed; there was a negligible effect on isometric strength. CONCLUSION: Low-intensity NMES-BFR induces muscle hypertrophy and strength gain in untrained young male participants.

A new two-step accurate CT-MRI fusion technique for post-implant prostate cancer.

PURPOSE: To develop an accurate method of fusing computed tomography (CT) with magnetic resonance imaging (MRI) for post-implant dosimetry after prostate seed implant brachytherapy. MATERIAL AND METHODS: Prostate cancer patients were scheduled to undergo CT and MRI after brachytherapy. We obtained the three MRI sequences on fat-suppressed T1-weighted imaging (FST1-WI), T2-weighted imaging (T2-WI), and T2*-weighted imaging (T2*-WI) in each patient. We compared the lengths and widths of 450 seed source images in the 10 study patients on CT, FST1-WI, T2-WI, and T2*-WI. After CT-MRI fusion using source positions by the least-squares method, we decided the center of each seed source and measured the distance of these centers between CT and MRI to estimate the fusion accuracy. RESULTS: The measured length and width of the seeds were 6.1 ± 0.5 mm (mean ± standard deviation) and 3.2 ± 0.2 mm on CT, 5.9 ± 0.4 mm, and 2.4 ± 0.2 mm on FST1-WI, 5.5 ± 0.5 mm and 1.8 ± 0.2 mm on T2-WI, and 7.8 ± 1.0 mm and 4.1 ± 0.7 mm on T2*-WI, respectively. The measured source location shifts on CT/FST1-WI and CT/T2-WI after image fusion in the 10 study patients were 0.9 ± 0.4 mm and 1.4 ± 0.2 mm, respectively. The shift on CT/FST1-WI was less than on CT/T2-WI (p = 0.005). CONCLUSIONS: For post-implant dosimetry after prostate seed implant brachytherapy, more accurate fusion of CT and T2-WI is achieved if CT and FST1-WI are fused first using the least-squares method and the center position of each source, followed by fusion of the FST1-WI and T2-WI images. This method is more accurate than direct image fusion.

Lung tumor motion change during stereotactic body radiotherapy (SBRT): an evaluation using MRI.

The purpose of this study is to investigate changes in lung tumor internal target volume during stereotactic body radiotherapy treatment (SBRT) using magnetic resonance imaging (MRI). Ten lung cancer patients (13 tumors) undergoing SBRT (48 Gy over four consecutive days) were evaluated. Each patient underwent three lung MRI evaluations: before SBRT (MRI-1), after fraction 3 of SBRT (MRI-3), and three months after completion of SBRT (MRI-3m). Each MRI consisted of T1-weighted images in axial plane through the entire lung. A cone-beam CT (CBCT) was taken before each fraction. On MRI and CBCT taken before fractions 1 and 3, gross tumor volume (GTV) was contoured and differences between the two volumes were compared. Median tumor size on CBCT before fractions1 (CBCT-1) and 3 (CBCT-3) was 8.68 and 11.10 cm3, respectively. In 12 tumors, the GTV was larger on CBCT-3 compared to CBCT-1 (median enlargement, 1.56 cm3). Median tumor size on MRI-1, MRI-3, and MRI-3m was 7.91, 11.60, and 3.33 cm3, respectively. In all patients, the GTV was larger on MRI-3 compared to MRI-1 (median enlargement, 1.54 cm3). In all patients, GTV was smaller on MRI-3m compared to MRI-1 (median shrinkage, 5.44 cm3). On CBCT and MRI, all patients showed enlargement of the GTV during the treatment week of SBRT, except for one patient who showed minimal shrinkage (0.86 cm3). Changes in tumor volume are unpredictable; therefore, motion and breathing must be taken into account during treatment planning, and image-guided methods should be used, when treating with large fraction sizes.