Published papers

Purpose: To report final results of a prospective study of stereotactic body radiation therapy (SBRT) in patients with previously untreated solitary primary hepatocellular carcinoma (HCC). Methods and Materials: This prospective, single-arm, multicenter phase 2 trial recruited patients with HCC who were unsuitable for, or refused, surgery and radiofrequency ablation, with 3-year overall survival rates as the primary endpoint and survival outcomes and adverse events as secondary endpoints. The prescribed SBRT dose was 40 Gy in 5 fractions. The final data were analyzed in November 2022. Results: Between 2014 and 2018, 36 patients (median age, 73.5 years) were registered; enrollment was closed before full recruitment due to slow accrual. Overall, 34 patients were analyzed for efficacy evaluation after excluding 2 patients. The median tumor size was 2.3 cm. The median follow-up times for all patients and for survivors were 49 and 56 months, respectively. The 3-year overall survival rate was 82% (95% confidence interval, 65%-92%). The 3-year local control rate was 93% (95% confidence interval, 76%-98%). Grade 3 or higher SBRT-related nonlaboratory toxicities were observed in 4 patients (11%). No grade 5 adverse events were observed. Conclusions: Final results of this phase 2 trial suggest the efficacy and safety of SBRT for newly diagnosed early-stage HCC that is unfit for other local therapies. Although this study was underpowered by the small number of registrations, the excellent results indicate that SBRT may be an alternative option for the management of early-stage HCC.

This is a prognostic report by the Japanese Breast Cancer Society on breast cancer extracted from the National Clinical Database-Breast Cancer Registry of Japan. Here, we present a summary of 457,878 breast cancer cases registered between 2004 and 2016. The median follow-up duration was 5.6 years. The median age at the start of treatment was 59 years (5–95%: 38–82 years) and increased from 57 years between 2004 and 2008 to 60 years between 2013 and 2016. The proportion of patients with Stage 0–II disease increased from 74.5% to 78.3%. The number of cases with estrogen and progesterone receptor positivity increased from 74.8% to 77.9% and 60.5% to 68.1%, respectively. Regarding (neo-)adjuvant chemotherapy, the taxane (T) or taxane-cyclophosphamide (C) regimen increased by 2.4% to 8.2%, but the (fluorouracil (F)) adriamycin (A)-C-T/(F) epirubicin (E)C-T and (F)AC/(F)EC regimens decreased by 18.6% to 15.2% and 13.5% to 5.0%, respectively. Regarding (neo-)adjuvant anti-human epidermal growth factor-2 (HER2)-targeted therapy, the use of trastuzumab increased from 4.6% to 10.5%. The rate of sentinel lymph node biopsy increased from 37.1% to 60.7%, while that of axillary dissection decreased from 54.5% to 22.6%. Improvements in disease-free and overall survival were observed in patients with HER2-positive breast cancer, but there was no apparent trend in patients with hormone receptor-positive, HER2-negative, or triple-negative breast cancers.

A correction to this paper has been published: https://doi.org/10.1007/s12282-021-01255-8

The Japanese Breast Cancer Society initiated the breast cancer registry in 1975, which transitioned to the National Clinical Database-Breast Cancer Registry in 2012. This annual report presents data from 2020 and analyzes the ten-year mortality rates for those aged 65 and older. We analyzed data from 93,784 breast cancer (BC) cases registered in 2020 and assessed 10-year mortality rates for 36,279 elderly patients diagnosed between 2008 and 2012. In 2020, 99.4% of BC cases were females with a median age of 61. Most (65%) were diagnosed at early stages (Stage 0 or I). Breast-conserving surgery rates varied with stages: 58.5% at cStage I, 30.8% at cStage II, and 13.1% at cStage III. Sentinel lymph node biopsy was done in 73.6% of cases, followed by radiotherapy in 70% of those post-conserving surgery and chemotherapy in 21.1% post-surgery. Pathology showed that 63.4% had tumors under 2.0 cm, 11.7% had pTis tumors, and 77.3% had no axillary lymph node metastasis. ER positivity was seen in 75.1%, HER2 in 14.3%, and 30% had a Ki67 positivity rate above 30%. Across all stages and subtypes, there was a trend where the 10-year mortality rates increased for individuals older than 65 years. In Stage I, many deaths were not directly linked to BC and, for those with HER2-type and triple-negative BC, breast cancer-related deaths increased with age. Within Stage II, patients older than 70 years with luminal-type BC often experienced deaths not directly linked to BC, whereas patients below 80 years with HER2-type and triple-negative BC, likely had breast cancer-related deaths. In Stage III, breast cancer-related deaths were more common, particularly in HER2 and triple-negative BC. Our prognostic analysis underscores distinct mortality patterns by stage, subtype, and age in elderly BC patients. It highlights the importance of personalized treatment strategies, considering subtype-specific aggressiveness, age-related factors, and comorbidities.

This annual report of the National Clinical Database-Breast Cancer Registry (NCD-BCR) by the Japanese Breast Cancer Society presents nationwide breast cancer statistics for patients registered in Japan in 2023. Among 107,372 patients with breast cancer at 1317 institutions, 99.3% were females with a median age of 62 years. The distribution of the clinical stages was as follows: stage 0 (15.5%); stage I (42.1%); stage II (31.1%); stage III (7.0%); and stage IV (2.1%). Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) positivity was observed in 78.9%, 70.0%, and 13.3% of patients, respectively. Among 102,717 patients without distant metastases, 41.2% underwent breast-conserving surgery, 76.5% underwent sentinel lymph node biopsy, and 6.0% underwent breast reconstruction. The distribution of radiotherapy was as follows: 75.2% received whole-breast irradiation, 15.7% chest-wall irradiation, and 20.7% regional irradiation. Among the 13,061 patients with pT1abN0M0 breast cancer, comprising 10,819 hormone receptor [HR]-positive/HER2-negative, 1479 HER2-positive and 763 HR-negative/HER2-negative individuals, 92.4% of HR-positive/HER2-negative patients received endocrine therapy, 46.9% of HER2-positive patients received chemotherapy and/or anti-HER2 therapy, and 31.2% of HR-negative/HER2-negative patients received chemotherapy. This annual report provides a nationwide overview of contemporary systemic therapy patterns in small breast cancer and highlights size‑dependent and subtype‑specific use of systemic therapy in Japan, reflecting a risk‑adapted treatment strategy.

Background: Precise target definition in prostate radiotherapy requires accurate computed tomography (CT)-magnetic resonance imaging (MRI) image registration using gold fiducial markers (GFMs). While multi-echo gradient recalled echo (ME GRE) sequences facilitate GFM identification, the quantitative impact of acquisition parameters on physical measurement accuracy remains insufficiently understood. Purpose: This study evaluates how MRI slice thickness and marker orientation angle jointly affect GFM visualization and geometric accuracy to characterize the resulting localization uncertainties. Methods: A kiwifruit-based phantom (T1: 1603.3 ms; T2: 72.3 ms) that mimics the relaxation times of the human prostate was imaged with 3.0T MRI. Imaging was performed using a 3D ME GRE sequence with three slice thicknesses (1.0, 2.0, and 3.0 mm) and 12 orientation angles ranging from horizontal to 90°. Five multidisciplinary observers independently identified marker coordinates while blinded to the acquisition parameters. Subjective confidence scores were also recorded. Results: Two-way analysis of variance (ANOVA) revealed significant main effects for slice thickness (F(2, 144) = 32.03, p < 0.001) and orientation angle (F(11, 144) = 4.06, p < 0.001), with significant interaction between them (F (22, 144) = 2.72, p < 0.001). Mean measurement errors with 95% confidence intervals (CI) were 0.96 mm (95% CI: 0.70–1.22) for 1.0 mm, 1.49 mm (95% CI: 1.23–1.75) for 2.0 mm, and 2.00 mm (95% CI: 1.74–2.26) for 3.0 mm slices. The peak error reached 3.10 mm under the combination of a 3.0 mm slice and 15° orientation. Subjective confidence scores showed a significant negative correlation with physical measurement errors (r = −0.296, p < 0.001). Conclusions: MRI slice thickness and marker orientation significantly impact GFM visualization accuracy. The results suggest that a 1.0 mm slice thickness offers a technical advantage for maintaining sub-millimeter localization accuracy across various marker orientations and highly desirable for high-precision radiotherapy planning.

近年の高精度放射線治療技術の進歩により,病変に高線量を照射しつつ肝実質への線量を低減することが可能となった。肝細胞癌のさまざまなステージで有効で安全な治療成績が報告されている。肝細胞癌にはさまざまな治療法があるが,放射線治療はとくに各治療の適応境界において一定の役割を果たし得る。複合免疫療法をはじめとした薬物療法が進歩したいま,改めて放射線治療を含めた局所治療の意義が問われるであろう。(著者抄録)

Purpose: Surgical resection of liver or pulmonary oligometastases (LP-OMD) in colorectal cancer (CRC) has been shown to improve survival. Stereotactic body radiotherapy (SBRT) is a promising alternative for patients with primary lung cancer. However, the efficacy of SBRT for LP-OMD in CRC remains inconclusive, and local control (LC) rates are often unsatisfactory. This prospective study aimed to evaluate the treatment outcomes of dose-escalated and convergent SBRT for patients with LP-OMD from CRC, with the goal of demonstrating its effectiveness as a treatment option for these patients. Methods and materials: This study included 23 CRC patients with LP-OMD who received SBRT between 2017 and 2022. The inclusion criteria were histologically confirmed colorectal adenocarcinoma, one to three oligometastases, and a tumor diameter of 5 cm or less. Patients who were inoperable or declined surgery were included. SBRT was delivered with total doses of 50–60 Gy administered over five fractions, covering the planning target volume surface within the 60% isodose line of the maximum dose. The primary endpoint was the 2-year LC rate, while secondary endpoints included overall survival (OS), progression-free survival (PFS), and toxicity. Results: The median follow-up duration was 41.0 months (range: 11.5–77.2). At the time of analysis, five patients had died from CRC, six were alive with disease, and twelve were alive without disease. Only one patient experienced local recurrence of a pulmonary oligometastasis. The 2-year LC, PFS, and OS rates were 95.0% (95% CI: 69.5–99.3), 61.3% (95% CI: 40.0–77.0), and 88.1% (95% CI: 67.6–96.0), respectively. Toxicity was acceptable, with no grade ≥ 3 adverse events. Conclusions: High-central-dose SBRT for LP-OMD from CRC achieved favorable local control with minimal toxicity. These findings should be interpreted cautiously and require validation in larger, multi-institutional studies.

背景.肝転移は小細胞肺癌で発生頻度が高く予後不良因子である.近年,海外を中心に肝臓への緩和照射の有用性が報告されているが,国内で報告例は少なく普及していない.症例.76歳男性.進展型小細胞肺癌に対し20XX-1年6月下旬からカルボプラチン+エトポシド+デュルバルマブ療法を開始,6コース完遂後にデュルバルマブ維持療法中だった.原発巣,肝転移,傍大動脈リンパ節転移の増大のため20XX年2月下旬に治療変更目的に入院した.Sensitive relapseと考えカルボプラチン+エトポシド療法を行ったが,背部痛と黄疸が出現し増強,オピオイドを開始した.多発肝転移増大に伴う被膜伸展症状であり疼痛緩和目的の全肝照射(21Gy/7fr)を行った.フレア現象で一過性疼痛増強がありオピオイドやステロイドを一時増量したが速やかに症状は軽快し独歩退院した.再入院しアムルビシン療法へ変更,全肝照射終了から約1ヵ月時点で症状は軽快し多発肝転移も縮小している.結論.小細胞肺癌は放射線感受性が高く,低線量照射で効果が得られた.低線量では放射線肝障害が起こりにくく全肝照射は治療抵抗性の小細胞肺癌でも有用と考える.(著者抄録)

症例は73歳女性.肺扁平上皮がん(cT3N3M0-Stage IIIC)に対し当科治療中.2022年6月より肺がん進行に伴い後腹膜リンパ節転移による腰背部痛が増強した.疼痛以外に両下肢浮腫による体動困難もあり7月8日に緊急入院し,後腹膜リンパ節転移に対して放射線治療(30Gy/10fr)を行った.タペンタドール200mg/日で疼痛管理を行っていたが入院中にフェンタニル貼付剤1200μg/日へ変更し腰背部痛は軽減した.また浮腫の原因疾患を鑑別し,理学所見・検査所見や病歴から,後腹膜リンパ節転移に関連したリンパ浮腫と診断した.入院31日目に浮腫は改善し,ベッド周囲のADLが向上し一時退院可能となった.リンパ節転移に関連したリンパ浮腫の治療方法は確立されておらず,放射線治療の有効性が報告されている.リンパ浮腫の診断に至るまでに他の病態を鑑別し,放射線治療によりリンパ浮腫が改善した1例を報告する.(著者抄録)

Background: In immediate expander/implant reconstruction, postmastectomy radiation therapy (PMRT) can be administered at two different time points: during tissue expander insertion or after exchange with an implant. The optimal timing for PMRT remains unclear. We conducted a systematic review and meta-analysis to evaluate the impact of PMRT timing on the outcomes of patients with breast cancer undergoing two-stage expander/implant breast reconstruction. Methods: A literature review of articles in English and Japanese up to March 2021 was performed using PubMed/MEDLINE, the Cochrane Library, and Ichushi-Web. Studies comparing the timing of PMRT in patients with breast cancer undergoing immediate two-stage expander/implant breast reconstructions and PMRT were included. The assessed outcomes included major complications, reconstruction failure, cosmesis, capsular contractures, and local recurrence. Results: Eleven studies encompassing 1,628 cases were identified. These included one prospective cohort study, one prospective case–control study, and nine retrospective cohort studies. No significant differences were observed in major complications between PMRT to expander and PMRT to implant (odds ratio [OR] 1.11, 95% confidence intervals [CI] 0.72–1.73, P = 0.64). Reconstruction failure was more prevalent in the expander group (OR 2.33, 95% CI 1.43–3.82, P = 0.0007), while severe capsular contractures occurred less frequently in the expander group (OR 0.33, 95% CI 0.12–0.92, P = 0.03). Conclusions: PMRT to expander was associated with higher reconstruction failure and lower severe capsular contracture rates, with no significant differences in major complications by timing. There is insufficient evidence to favor one approach over the other.

肝細胞がん(hepatocellular carcinoma:HCC)は,世界的に主要ながん死因の一つであり,日本においても依然として死亡率の高い疾患である。特に,C型肝炎ウイルス(HCV)やB型肝炎ウイルス(HBV)などの感染に伴う肝硬変を背景として発症することが多いが,近年では飲酒や脂肪肝による慢性肝障害もがん化の原因として増加しており,高齢化とともに治療選択の幅の重要性は増加している。HCCの局所治療は,切除,局所療法[ラジオ波焼灼療法(RFA)やマイクロ波凝固療法(MWA)],肝動脈化学塞栓療法(TACE)など多岐にわたるが,これらが非適応の症例に対する治療として,放射線治療(radiotherapy),特に体幹部定位放射線治療(stereotactic body radiation therapy:SBRT)が注目されている。SBRTは,短期間で高線量を腫瘍に集中的に照射する技術であり,非侵襲性と高い制御率が特徴である。本稿では,HCCに対するSBRTの現状とエビデンス,および今後の展望について論じる。(著者抄録)

PURPOSE: Clear evidence indicating whether surgery or stereotactic body radiation therapy (SBRT) is best for non-small-cell lung cancer (NSCLC) is lacking. SBRT has many advantages. We used artificial neural networks (NNs) to predict treatment outcomes for patients with NSCLC receiving SBRT, aiming to aid in decision making. PATIENTS AND METHODS: Among consecutive patients receiving SBRT between 2005 and 2019 in our institution, we retrospectively identified those with Tis-T4N0M0 NSCLC. We constructed two NNs for prediction of overall survival (OS) and cancer progression in the first 5 years after SBRT, which were tested using an internal and an external test data set. We performed risk group stratification, wherein 5-year OS and cancer progression were stratified into three groups. RESULTS: In total, 692 patients in our institution and 100 patients randomly chosen in the external institution were enrolled. The NNs resulted in concordance indexes for OS of 0.76 (95% CI, 0.73 to 0.79), 0.68 (95% CI, 0.60 to 0.75), and 0.69 (95% CI, 0.61 to 0.76) and area under the curve for cancer progression of 0.80 (95% CI, 0.75 to 0.84), 0.72 (95% CI, 0.60 to 0.83), and 0.70 (95% CI, 0.57 to 0.81) in the training, internal test, and external test data sets, respectively. The survival and cumulative incidence curves were significantly stratified. NNs selected low-risk cancer progression groups of 5.6%, 6.9%, and 7.0% in the training, internal test, and external test data sets, respectively, suggesting that 48% of patients with peripheral Tis-4N0M0 NSCLC can be at low-risk for cancer progression. CONCLUSION: Predictions of SBRT outcomes using NNs were useful for Tis-4N0M0 NSCLC. Our results are anticipated to open new avenues for NN predictions and provide decision-making guidance for patients and physicians.