A Japanese multi-institutional phase II study of moderate hypofractionated intensity-modulated radiotherapy with image-guided technique for prostate cancer.

BACKGROUND: The aim of this multi-institutional phase II study was to confirm the safety and the potential efficacy of moderately hypofractionated intensity-modulated radiotherapy (IMRT) with prostate-based image-guidance for Japanese patients. METHODS: Patients with low- or intermediate-risk localized prostate cancer were eligible. Patients with a part of high risk (having only one of the following factors, cT3a, 20 < PSA ≤ 30, or GS = 8 or 9) were also included. Hypofractionated IMRT using daily image-guided technique with prostate matching was performed with a total dose of 70 Gy in 28 fractions. Neoadjuvant hormonal therapy for 4-8 months was mandatory for patients with intermediate or high-risk prostate cancer. RESULTS: From 20 institutions, 134 patients enrolled. The median follow-up was 5.16 years (range, 1.43-6.47 years). The number of patients with low, intermediate, and high-risk prostate cancer was 20, 80, and 34, respectively. The 5-year overall, biochemical failure-free, and clinical failure-free survival was 94.5%, 96.0%, and 99.2%, respectively. The 5-year biochemical failure-free survival for patients with low-, intermediate-, and high-risk disease was 94.1%, 97.4%, and 93.9%, respectively. The incidences of grade 2 gastrointestinal (GI) and genitourinary (GU) late toxicities at 5 years were 5.3% and 5.3%, respectively. There are no acute or late toxicities ≥ grade 3. Of 124 patients who were followed for up to 5 years, the grade 2 late GU or GI toxicities were 10.5% (90% confidence intervals, 6.3-16.2%, p = 0.0958). CONCLUSION: The safety and efficacy of moderately hypofractionated IMRT with prostate-based image-guidance was confirmed among Japanese patients with prostate cancer.

Dose and organ displacement comparisons with breast conservative radiotherapy using abdominal and thoracic deep-inspiration breath-holds: A comparative dosimetric study.

Deep-inspiration breath-hold (DIBH) reduces the radiation dose to the heart and lungs during breast radiotherapy in cancer. However, there is not enough discussion about suitable breathing methods for DIBH. Therefore, we investigated the radiation doses and organ and body surface displacement in abdominal DIBH (A-DIBH) and thoracic DIBH (T-DIBH). Free-breathing, A-DIBH, and T-DIBH computed tomography images of 100 patients were used. After contouring the targets, heart, and lungs, radiotherapy plans were created. We investigated the heart and lung doses, the associations between the heart and left lung displacements, and the thorax and abdominal surface displacements. No significant differences were observed in the target dose indices. However, the heart and lung doses were significantly lower in A-DIBH than in T-DIBH for all the indices; the mean heart and lung doses were 1.69 and 3.48 Gy, and 1.91 and 3.55 Gy in A-DIBH and T-DIBH, respectively. The inferior displacement of the heart and the left lung was more significant in A-DIBH. Therefore, inferior expansion of the heart and lungs may be responsible for the respective dose reductions. The abdominal surface displaced more than the thoracic surface in both A-DIBH and T-DIBH, and thoracic surface displacement was greater in T-DIBH than in A-DIBH. Moreover, A-DIBH can be identified because abdominal surface displacement was greater in A-DIBH than in T-DIBH. In conclusion, A-DIBH and T-DIBH could be distinguished by comparing the abdominal and thoracic surfaces of A-DIBH and T-DIBH, thereby ensuring the implementation of A-DIBH and reducing the heart and lung doses.

Examination of the dose distribution of volumetric modulated arc radiotherapy using a high-definition multi-leaf collimator for breast cancer patients with irradiated regional lymph nodes.

Background: A high-definition multi-leaf collimator (HD-MLC) with 5- and 10-mm fine MLCs is useful for radiotherapy. However, it is difficult to irradiate the mammary gland and supraclavicular region using a HD-MLC because of the narrow field of volumetric modulated arc radiotherapy (VMAT). Therefore, we aimed to evaluate the dose distribution of the VMAT dose using a HD-MLC in 15 patients with left breast cancer undergoing postoperative irradiation of breast and regional lymph nodes, including the internal mammary node. Materials and methods: The following four plans were generated: three-arc VMAT using HD-MLC (HD-VMAT), two tangential arcs and one-arc VMAT using HD-MLC (tHD-VMAT), three-dimensional conformal radiotherapy (3DCRT) using HD-MLC, and two-arc VMAT using the Millennium 120-leaf MLC (M-VMAT). We assessed the doses to the target volume and organs at risk. Results: The target dose distributions were higher for HD-VMAT than 3DCRT. There were no significant differences in the heart mean dose (Dmean) or lung volume receiving 20 Gy (V20 Gy) between HD-VMAT and 3DCRT. The heart Dmean and lung V20 Gy of tHD-VMAT were higher than those of HD-VMAT, and the heart Dmean of M-VMAT was higher than that of HD-VMAT. However, the target doses of tHD-VMAT, M-VMAT, and HD-VMAT were equivalent. Conclusions: In cases of the mammary gland and regional lymph node irradiation, including the internal mammary node in patients with left breast cancer, HD-VMAT was not inferior to M-VMAT and provided a better dose distribution to the target volume and organs at risk compared with 3DCRT and tHD-VMAT.

Visual Hallucinations and Impaired Conscious Visual Perception in Parkinson Disease.

Visual hallucinations (VHs) are common in patients with Parkinson disease (PD), especially those with dementia, whereas auditory hallucinations are quite rare. Recent studies have revealed the involvement of several regions along the visual information-processing system that contribute to the pathophysiological mechanism of VHs: the eyes and retina, retinofugal projection, lateral geniculate nucleus, striate cortex, ventral pathways in the temporal cortices, and frontal and parietal cortices. In addition, the concurrent involvement of other systems in the brainstem and basal forebrain further modify VHs in PD. In this review, we discuss the pathophysiological association between the regional involvement of these areas and VHs.

Analysis of key clinical features for achieving complete remission in stage III and IV non-small cell lung cancer patients.

BACKGROUND: Although development of immune checkpoint inhibitors and various molecular target agents has extended overall survival time (OS) in advanced non-small cell lung cancer (NSCLC), a complete cure remains rare. We aimed to identify features and treatment modalities of complete remission (CR) cases in stages III and IV NSCLC by analyzing long-term survivors whose OS exceeded 3 years. METHODS: From our hospital database, 1,699 patients, registered as lung cancer between 1st Mar 2004 and 30th Apr 2011, were retrospectively examined. Stage III or IV histologically or cytologically confirmed NSCLC patients with chemotherapy initiated during this period were enrolled. A Cox proportion hazards regression model was used. Data collection was closed on 13th Feb 2017. RESULTS: There were 164 stage III and 279 stage IV patients, including 37 (22.6%) and 51 (18.3%) long-term survivors and 12 (7.3%) and 5 (1.8%) CR patients, respectively. The long-term survivors were divided into three groups: 3 ≤ OS < 5 years, 5 years ≤ OS with tumor, and 5 years ≤ OS without tumor (CR). The median OS of these groups were 1,405, 2,238, and 2,876 days in stage III and 1,368, 2,503, and 2,643 days in stage IV, respectively. The mean chemotherapy cycle numbers were 16, 20, and 10 in stage III and 24, 25, and 5 in stage IV, respectively. In the stage III CR group, all patients received chemoradiation, all oligometastases were controlled by radiation, and none had brain metastases. Compared with non-CR patients, the stage IV CR patients had smaller primary tumors and fewer metastases, which were independent prognostic factors for OS among long-term survivors. The 80% stage IV CR patients received radiation or surgery for controlling primary tumors, and the surgery rate for oligometastases was high. Pathological findings in the stage IV CR patients revealed that numerous inflammatory cells existed around and inside resected lung and brain tumors, indicating strong immune response. CONCLUSIONS: Multiple line chemotherapies with primary and oligometastatic controls by surgery and/or radiation might achieve cure in certain advanced NSCLC. Cure strategies must be changed according to stage III or IV. This study was retrospectively registered on 16th Jun 2019 in UMIN Clinical Trials Registry (number UMIN000037078).

To what extent does the EQ-5D-3L correlate with the FACT-H&N of patients with oral cancer during the perioperative period?

BACKGROUND: The EuroQol 5-dimension scale (EQ-5D) is one of the most frequently used preference-based quality of life (QOL) measures for health technology assessment. The 3-level version of the EQ-5D comprises a descriptive system (the EQ-5D-3L) and a visual analog scale (EQ-VAS). It remains unclear whether this five-item scale correlates with the QOL of patients with oral cancer during the perioperative period. We sought to clarify this point in the present study. METHODS: Participants were 84 patients with oral malignancies who underwent radical treatment and completed the EQ-5D-3L and Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) at regular intervals over 3 months after treatment. We analyzed the correlations between the EQ-5D-3L, EQ-VAS, and FACT-H&N, and conducted multiple regression analyses to examine how the FACT-H&N subscales relate to the EQ-5D-3L and EQ-VAS. We also investigated whether the EQ-5D-3L shows ceiling effects. RESULTS: The EQ-5D-3L and EQ-VAS were strongly correlated with the FACT-H&N (rs = 0.621 and 0.638, respectively; P < 0.01). Furthermore, the EQ-5D-3L was significantly related with all FACT-H&N subscales except for social/family well-being. Particularly, the physical well-being subscale had the strongest relationship with the EQ-5D-3L. The FACT H&N and EQ-5D-3L showed similar changes over time. The EQ-5D-3L did not have a ceiling effect statistically. CONCLUSIONS: Our results indicate that actual physical performance might be most important for cost-utility analysis, whereas the assessment of familial feelings or friendship seems less important. However, the EQ-5D-3L appears to generally correlate with the FACT-H&N of patients with oral cancer during the perioperative period. Therefore, it is reasonable to assess the cost performance of oral cancer treatment using the EQ-5D-3L in Japan.

Outcomes of Local Excision plus Chemoradiotherapy in Patients with T1 Rectal Cancer.

OBJECTIVE: The National Comprehensive Cancer Network (NCCN) guidelines recommend local excision and observation as standard treatment for selected patients with clinical T1N0M0 rectal cancer. In patients with pathological T1 (pT1) rectal cancer who received local excision, the local recurrence rate is at least 10%. We studied oncological outcomes in patients with pT1 rectal cancer who received chemoradiotherapy (CRT) after local excision. METHODS: Local excision was performed in 65 patients with clinical T1N0M0 rectal cancer (≤8 cm from the anal verge, tumor size < 30 mm, well or moderately differentiated adenocarcinoma). The patients received CRT (40 or 45 Gy in 1.8-2.0 fractions with concurrent oral UFT [tegafur/uracil] or S-1 [tegafur/gimeracil/ote-racil]) after confirmation of pT1 and negative margins. RESULTS: Patients who had pT2 cancer or who did not provide informed consent were excluded. The remaining 50 patients additionally received CRT. The CRT was completed in 48 patients (96%). The median follow-up period was 71 months. Local recurrence occurred in 1 patient (2%). Distant metastases occurred in 3 patients (6%). The 5-year disease-free survival rate was 86%, and the 5-year overall survival rate was 92%. CONCLUSIONS: Our study suggested that multidisciplinary treatment with local excision plus CRT can be used as a treatment option in selected patients with clinical T1N0M0 rectal cancer.

Mucinous components assessed by magnetic resonance imaging in primary rectal cancer tissue before and after chemoradiotherapy and tumor response.

BACKGROUND: Mucinous rectal carcinoma has been reported to have a lower survival rate and a poorer histologic response to chemoradiotherapy(CRT). Magnetic resonance imaging (MRI) can accurately evaluate the amount of mucin pools (MP) in primary cancer tissue. We compared the degree of MP on MRI before and after CRT with the histologic findings of resected specimens to investigate the predictors of response to CRT. METHODS: The study group comprised 205 patients with rectal adenocarcinoma who received preoperative CRT. MPs were measured on MRI before and after CRT and in resected specimens. The degree of MP was classified into five classes according to the MP area ratio: 0%, class I; 1 to 19%, class II; 20 to 49%, class III; and 50% or higher, class IV. RESULTS: The degree of MP on MRI was largely unchanged after CRT; however, the MP on MRI after CRT was underestimated in 26.3% of patients as compared with that in resected specimens. A pathological complete response was obtained in patients who initially had no MP or had an MP ratio of less than 20%. The tumor volume was significantly greater, and the rates of tumor shrinkage and T downstaging were significantly lower in patients who had an MP area ratio of 20% or higher before CRT than in those who had an MP area ratio of less than 20%. CONCLUSIONS: The MP area ratio measured on MRI before treatment was closely associated with the response to CRT and is a potentially useful predictor of treatment response.

Longitudinal changes in the quality of life of oral cancer patients during the perioperative period.

BACKGROUND: There are few quality of life (QOL) studies that have focused on the experiences of oral cancer patients. Therefore, the present study aimed to investigate how the QOL for patients with oral cancer changed perioperatively. METHODS: Eighty-three participants undergoing radical therapy completed assessments of QOL at pre-treatment, treatment completion, and 1-, 3-, and 6-months post-treatment. The Japanese version of the FACT-H&N, comprising the subscales of "physical well-being (PWB)," "social/family well-being (SWB)," "emotional well-being (EWB)," "functional well-being (FWB)," and "additional head- and neck-specific concerns(HN)" was used to assess QOL. There were two study groups: those who required reconstructive surgery (r+, 31 patients) and those who did not (r-, 52 patients). RESULTS: The FACT-H&N, PWB, FWB, and HN, were lowest at treatment completion due to declines; then, it showed significant improvement over time (p < 0.05). SWB was the highest at the completion of treatment, and thereafter decreased significantly until 3 months after treatment (p < 0.05). EWB was the lowest before treatment but improved over time (p < 0.01). HN was significantly lower at 6 months after treatment than before treatment (p < 0.05). The QOL of the r+ group was significantly lower than that of the r- group (p < 0.01). CONCLUSIONS: The treatment-associated declines in subscale area may be compensated for by gains in other subscale areas. Psychological support is better introduced prior to cancer treatment. As it is often difficult to recover from declines in HN functioning subscale, strategies that promote compensation in other areas must be explored. Clinicians should become thoroughly familiar with how patients' QOL changes over time and provide holistic treatments that honor patients' autonomy.

A Modified Classification of Prognostic Factors Based on Pathological Stage and Tumor Regression Grade in Patients with Rectal Cancer Who Receive Preoperative Chemoradiotherapy.

OBJECTIVE: The histologic response to neoadjuvant chemoradiotherapy (CRT) has been intimately related to outcomes in locally advanced rectal cancer. However, reliable prognostic factors have yet to be established. SUBJECTS AND METHODS: The study group comprised 198 patients with locally advanced rectal cancer who received CRT. A modified classification based on the combination of ypStage and tumor regression grade (TRG) was developed. ypStage II with TRG 2 was classified as ypTRGstage IIA, and ypStage II with TRG 3 or 4 was classified as ypTRGstage IIB. ypStage 0 and ypStage I were classified as ypTRGstage I, and ypStage III was classified as ypTRGstage III. RESULTS: The 5-year disease-free survival (DFS) was 83% in ypTRGstage I, 86% in ypTRGstage IIA, 57% in ypTRGstage IIB, and 60% in ypTRGstage III (p = 0.0001). The 5-year DFS in ypTRGstage IIA did not differ significantly from that in ypStage 0 (p = 0.865) or ypStage I (p = 0.585). The 5-year DFS in ypStage IIB did not differ from that in ypStage III (p = 0.912). Multivariate analysis showed that ypTRGstage was an independent risk factor for DFS. CONCLUSION: A modified classification allows patients with ypStage II locally advanced rectal cancer to be clearly divided into two groups: responders and nonresponders.

Phase II study of preoperative concurrent chemoradiotherapy with S-1 plus bevacizumab for locally advanced resectable rectal adenocarcinoma.

OBJECTIVE: A single-arm phase II clinical trial was conducted to evaluate the safety and efficacy of preoperative chemoradiotherapy (CRT) with concurrent S-1, bevacizumab, and radiation in patients with locally advanced rectal cancer (LARC). METHODS: Fifty-two patients with LARC were enrolled. A total dose of 45 Gy was delivered in 25 fractions over 5 weeks, S-1 was administered orally twice a day on days 1-14 and 22-35, and bevacizumab was administered on days 1, 15, and 29. Surgical resection was scheduled 8 weeks (6-10 weeks) after completing the CRT. RESULTS: All 52 patients underwent R0 radical surgery. Sphincter preservation was possible in 38 (73.1%) patients. A pathologic complete response was obtained in 10 (19.2%) patients, a pathologic downstaging was achieved in 37 (71.2%) patients, and the tumor shrinkage rate was 77.1%. The only grade 3 adverse events were leukopenia and rash in 1 (1.9%) patient. The rate of postoperative complications was 28.8%. Anastomotic leakage occurred in 9 (23.7%) of the 38 patients who underwent sphincter-preserving surgery. Perineal wound dehiscence developed in 2 (14.3%) of the 14 patients who received an abdominoperineal resection. CONCLUSIONS: Adding bevacizumab to S-1 clearly increased the incidence of wound-related complications, with no distinct enhancement of tumor response.

Predictive markers of chemoradiotherapy for rectal cancer: comparison of biopsy specimens taken before and about 1 week after the start of chemoradiotherapy.

BACKGROUND: Preoperative chemoradiotherapy (CRT) significantly decreases local recurrence in patients with rectal cancer. Although various biomarkers in biopsy specimens obtained before starting CRT have been examined, reliable prognostic factors have yet to be established. We tested the hypothesis that biopsy specimens obtained soon after the start of CRT can be used as prognostic factors. METHODS: Preoperative CRT was given to 70 consecutive patients with rectal cancer. Biopsies were taken before and about 7 days after starting CRT. The specimens were stained with hematoxylin and eosin (HE), and the expressions of Ki67, p53, and p21 and apoptosis were evaluated immunohistochemically. RESULTS: The expressions of Ki67, p53, and p21 and apoptosis before treatment were not significantly related to histologic response or tumor shrinkage. In specimens obtained about 7 days after CRT began, marked histologic regression was significantly higher in p21-positive, apoptosis-positive cases, and in cases with moderate changes on HE specimens (p = 0.017, p = 0.010, and p = 0.004, respectively). The tumor shrinkage was significantly higher in apoptosis-positive cases and cases with moderate changes on HE specimens (p = 0.002 and p < 0.001, respectively). Disease-free survival (DFS) was significantly higher in patients who had marked regression than in those who did not (p = 0.019). DFS was also significantly higher in patients with moderate changes on HE specimens than in those with mild changes (p = 0.016). CONCLUSIONS: Changes on HE-stained biopsy specimens obtained about 1 week after starting CRT are a reliable prognostic factor, similar to histologic marked regression in resected specimens; a major advantage is that the former results are available at an early phase.

Relationship between histologic response and the degree of tumor shrinkage after chemoradiotherapy in patients with locally advanced rectal cancer.

BACKGROUND: Preoperative chemoradiotherapy (CRT) significantly decreases local recurrence in advanced rectal cancer. We studied whether the degree of tumor shrinkage can be used as a predictor of histologic response. METHODS: The subjects were 114 patients with locally advanced rectal cancer who underwent total mesorectal excision after receiving radiotherapy combined with uracil/tegafur (UFT) or S-1. The degree of tumor shrinkage based on barium enema examination and magnetic resonance imaging (MRI) were assessed before CRT and immediately before surgery. RESULTS: A histologic complete response (ypCR), histologic marked regression, T and N downstaging were associated with significantly higher tumor-shrinkage rates on barium enema (P < 0.01, P < 0.01, P < 0.01, and P < 0.01, respectively) as well as on MRI (P < 0.01, P < 0.01, P < 0.01, and P = 0.01, respectively). On multivariate analysis, ypCR and histologic marked regression were significantly related only to tumor-shrinkage rates on barium enema (P < 0.01 and P < 0.01, respectively), and were not related to tumor-shrinkage rates on MRI. CONCLUSIONS: The degree of tumor shrinkage is closely related to the final histologic response. Two-dimensionally evaluated tumor-shrinkage rates based on barium enema are adequate for the prediction of histologic response.

Local control correlates with overall survival in radiotherapy for early-stage non-small cell lung cancer: A systematic review.

PURPOSE: Local control (LC) is an important outcome of local cancer therapy, besides overall survival (OS). We conducted a comprehensive literature search to investigate whether a high LC rate contributes to good OS in radiotherapy for early-stage non-small cell lung cancer (ES-NSCLC). MATERIALS AND METHODS: Studies in patients receiving radiotherapy for peripheral ES-NSCLC, mainly staged as T1-2N0M0 were included for a systematic review. Relevant information was collected including, dose fractionation, T stage, median age, 3-year LC, cancer-specific survival (CSS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and OS. Correlations between outcomes and clinical variables were evaluated. RESULTS: After screening, 101 data points from 87 studies including 13,435 patients were selected for the quantitative synthesis. Univariate meta-regression analysis revealed that the coefficients between the 3-year LC and 3-year DFS, DMFS, CSS, and OS were 0.753 (95% confidence interval (CI): 0.307-1.199; p < 0.001), 0.360 (95% CI: 0.128-0.593; p = 0.002), 0.766 (95% CI: 0.489-1.044; p < 0.001), and 0.574 (95% CI: 0.275-0.822; p < 0.001), respectively. Multivariate analysis revealed that the 3-year LC (coefficient, 0.561; 95% CI: 0.254-0.830; p < 0.001) and T1 proportion (coefficient, 0.207; 95% CI: 0.030-0.385; p = 0.012) were significantly associated with the 3-year OS and CSS (coefficient for 3-year LC, 0.720; 95% CI: 0.468-0.972; p < 0.001 and T1 proportion, 0.002; 95% CI: 0.000-0.003; p = 0.012). Toxicities ≥ grade 3 were low (3.4%). CONCLUSIONS: Three-year LC was correlated with three-year OS in patients receiving radiotherapy for ES-NSCLC. A 5% increase in 3-year LC is expected to improve the 3-year CSS and OS rates by 3.8% and 2.8%, respectively.

Factors Involved in the Choice Between Thoracic and Abdominal Deep Inspiration Breath Holds During Left Breast Cancer Radiotherapy.

PURPOSE: Deep inspiration breath hold (DIBH) is used with adjuvant radiation therapy after left breast cancer surgery to reduce radiation dose to the heart. In this study we determined whether thoracic DIBH (T-DIBH) or abdominal DIBH (A-DIBH) should be selected based on patient background. METHODS: Three-dimensional conformal radiation therapy plans were created under the same conditions using free breathing (FB), T-DIBH, and A-DIBH CT scans of patients who had previously undergone treatment at our hospital. RESULTS: A-DIBH decreased the left lung dose compared to FB. In comparing T-DIBH and A-DIBH, the heart maximum and left lung doses were significantly lower in A-DIBH. The differences in the heart mean dose (Dmean) between FB, and T-DIBH and A-DIBH were correlated with the cardiothoracic ratio, heart volume, and left lung volume. The difference in the heart Dmean and the left lung dose of T-DIBH and A-DIBH correlated with the forced vital capacity (FVC). CONCLUSIONS: A-DIBH is preferable over T-DIBH with respect to the heart and left lung doses; however, with respect to the heart Dmean, T-DIBH was more effective in reducing the dose in some cases, and the FVC was a relevant factor in this study.

Effect on Heart and Lung Doses Reduction of Abdominal and Thoracic Deep Inspiratory Breath-hold Assuming Involved-field Radiation Therapy in Patients with Simulated Esophageal Cancer.

PURPOSE: The purpose of this study was to evaluate the lung and heart doses in volumetric-modulated arc therapy (VMAT) using involved-field irradiation in patients with middle-to-lower thoracic esophageal cancer during free breathing (FB), abdominal deep inspiratory breath-hold (A-DIBH), and thoracic DIBH (T-DIBH) images. METHODS: Computed tomography images of A-DIBH, T-DIBH, and FB from 25 patients with breast cancer were used to simulate patients with esophageal cancer. The irradiation field was set at an involved-field, and target and risk organs were outlined according to uniform criteria. VMAT optimization was performed, and lung and heart doses were evaluated. RESULTS: A-DIBH had a lower lung V20 Gy than FB and a lower lung V40 Gy, V30 Gy, V20 Gy than T-DIBH. The heart all dose indices were lower in T-DIBH than FB, and the heart V10 Gy was lower in A-DIBH than FB. However, the heart Dmean was comparable with A-DIBH and T-DIBH. CONCLUSIONS: A-DIBH had significant dose advantages for lungs compared to FB and T-DIBH, and the heart Dmean was comparable to T-DIBH. Therefore, when performing DIBH, A-DIBH is suggested for radiotherapy in patients with middle-to-lower thoracic esophageal cancer, excluding irradiation of the prophylactic area.

Re-irradiation for metastatic brain tumors with whole-brain radiotherapy.

OBJECTIVE: To determine whether second whole-brain irradiation is beneficial for patients previously treated with whole-brain irradiation. METHODS: A retrospective analysis was done for 31 patients with brain metastases who had undergone re-irradiation. Initial whole-brain irradiation was performed with 30 Gy/10 fractions for 87% of these patients. Whole-brain re-irradiation was performed with 30 Gy/10 fractions for 42% of these patients (3-40 Gy/1-20 fractions). Three patients underwent a third whole-brain irradiation. RESULTS: The median interval between the initial irradiation and re-irradiation was 10 months (range: 2-69 months). The median survival time after re-irradiation was 4 months (range: 1-21 months). The symptomatic improvement rate after re-irradiation was 68%, and the partial and complete tumor response rate was 55%. Fifty-two percent of the patients developed Grade 1 acute reactions. On magnetic resonance imaging, brain atrophy was observed in 36% of these patients after the initial irradiation and 74% after re-irradiation. Grade ≥2 encephalopathy or cognitive disturbance was observed in 10 patients (32%) after re-irradiation. Based on univariate analysis, significant factors related to survival after re-irradiation were the location of the primary cancer (P = 0.003) and the Karnofsky performance status at the time of re-irradiation (P = 0.008). A Karnofsky performance status ≥70 was significant based on multivariate analysis (P = 0.050). CONCLUSIONS: Whole-brain re-irradiation for brain metastases placed only a slight burden on patients and was effective for symptomatic improvement. However, their remaining survival time was limited and the incidence of cognitive disturbance was rather high.

Relationship between Dose Prescription Methods and Local Control Rate in Stereotactic Body Radiotherapy for Early Stage Non-Small-Cell Lung Cancer: Systematic Review and Meta-Analysis.

Variations in dose prescription methods in stereotactic body radiotherapy (SBRT) for early stage non-small-cell lung cancer (ES-NSCLC) make it difficult to properly compare the outcomes of published studies. We conducted a comprehensive search of the published literature to summarize the outcomes by discerning the relationship between local control (LC) and dose prescription sites. We systematically searched PubMed to identify observational studies reporting LC after SBRT for peripheral ES-NSCLC. The correlations between LC and four types of biologically effective doses (BED) were evaluated, which were calculated from nominal, central, and peripheral prescription points and, from those, the average BED. To evaluate information on SBRT for peripheral ES-NSCLC, 188 studies were analyzed. The number of relevant articles increased over time. The use of an inhomogeneity correction was mentioned in less than half of the articles, even among the most recent. To evaluate the relationship between the four BEDs and LC, 33 studies were analyzed. Univariate meta-regression revealed that only the central BED significantly correlated with the 3-year LC of SBRT for ES-NSCLC (p = 0.03). As a limitation, tumor volume, which might affect the results of this study, could not be considered due to a lack of data. In conclusion, the central dose prescription is appropriate for evaluating the correlation between the dose and LC of SBRT for ES-NSCLC. The standardization of SBRT dose prescriptions is desirable.

Comparing the toxicity and disease control rate of radiotherapy for prostate cancer between salvage settings after high-intensity focused ultrasound therapy and initial settings.

The purpose of this retrospective study was to compare the toxicity and disease control rate of radiotherapy for prostate cancer in salvage settings after high-intensity focused ultrasound (HIFU) therapy (HIFU cohort) with those in radical settings (non-HIFU cohort). From 2012 to 2020, 215 patients were identified for this study and 17 were treated in the salvage settings after HIFU. The median follow-up time was 34.5 months (range: 7-102 months, inter-quartile range [IQR]: 16-64 months). Genitourinary (GU) and gastrointestinal (GI) adverse events were evaluated in acute and late periods with Common Terminology Criteria for Adverse Events version 5, and the rates of biochemical-clinical failure free survival (BCFS) and overall survival (OS) were estimated. The cumulative incidence of late GU Grade 2 or greater toxicity after five years was significantly different between the non-HIFU and HIFU cohorts with rates of 7.3% and 26.2%, respectively (P = 0.03). Regarding GI Grade 2 or greater toxicity, there was no significant difference between the two cohorts. The 5y-BCFS was 84.2% in the non-HIFU cohort and 69.5% in the HIFU cohort with no significant difference (P = 0.10) and the 5y-OS was 95.9% and 92.3%, respectively (P = 0.47). We concluded that the possibility of increased late GU Grade 2 or greater should be considered when applying salvage radiotherapy for local recurrence after HIFU.

Phase I/II study of preoperative concurrent chemoradiotherapy with S-1 for locally advanced, resectable rectal adenocarcinoma.

PURPOSE: To assess the maximum tolerability of a combination of S-1 and preoperative radiotherapy and to evaluate the feasibility and activity in patients with locally advanced rectal cancer. METHODS: Patients (n = 30) with adenocarcinoma of the middle or lower rectum were enrolled in a phase I (n = 9) and/or phase II (n = 21) trial. A total dose of 45 Gy was delivered in 25 fractions over 5 weeks, and S-1 was orally administered twice a day on days 1-14 and 22-35. Surgical resection was scheduled 4-8 weeks after the completion of chemoradiation. RESULTS: In phase I, the recommended dose (RD) of S-1 was 80 mg/m(2)/day, and the maximum-tolerated dose was never reached. A total of 27 cases, including the 6 RD cases in phase I, were enrolled in phase II. In phase II, a pathological complete response (pCR) was observed in 6/27 patients (22%), pathological downstaging was observed in 21/27 patients (78%), and a tumor volume reduction of 69 ± 22% was obtained. These results were similar to the previously reported pCR rates of 16-18%, pathological downstaging rates of 49-59%, and tumor volume reduction of 68% after chemoradiotherapy with capecitabine. Grade 3 adverse events consisted of one case of leukopenia (4%), 2 cases of anemia (7%) and 3 cases of diarrhea (11%). Overall, the adverse events were very mild. Hand-foot syndrome was not observed. CONCLUSION: The efficacy of chemoradiotherapy with S-1 seems to be equivalent to the efficacy reported for chemoradiotherapy with capecitabine, but the adverse events were much milder, although further study is warranted.