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Introduction This study aimed to describe the course of patients with lung cancer from treatment initiation to end-of-life. Methods This retrospective cohort study used Claims Data from the National Health Insurance and Advanced Elderly Medical Service System. We analyzed data from patients newly diagnosed with lung cancer between April 2013 and March 2021 who had been hospitalized at our University Hospital in urban area. We evaluated (1) treatment courses of these patients, and (2) end-of-life care and clinical factors related to end-of-life care. Results A total of 818 patients who were diagnosed with lung cancer and received lung cancer treatment were included, of whom 200 were assessed for end-of-life. During the study period, 464 patients underwent surgery, while 308 received chemotherapy without undergoing surgery. The patients generally received lung cancer treatment within 2 years. The median time from initial treatment to death was 13 months for deceased patients. Patients in the palliative care unit (PCU) constituted 9% at 30 days before death, 25% at 7 days before death, and 40.5% on the day of death, whereas only 15% died at home. The prevalence of end-of-life care in the home/PCU was elevated among patients receiving molecular targeted drugs and in the female group. Conclusion This study highlighted the patterns of end-of-life care following lung cancer treatment by using Claims Data. PCU utilization was concentrated in the period shortly before death, with fewer patients passing away at home. End-of-life care may be influenced by clinical factors, including the type of lung cancer treatment received, which may change the place of care.

Abstract We aimed to retrospectively review outcomes in patients with high-risk prostate cancer and a Gleason score ≤ 6 following modern radiotherapy. We analyzed the outcomes of 1374 patients who had undergone modern radiotherapy, comprising a high-risk low grade [HRLG] group (Gleason score ≤ 6; n = 94) and a high-risk high grade [HRHG] group (Gleason score ≥ 7, n = 1125). We included 955 patients who received brachytherapy with or without external beam radio-therapy (EBRT) and 264 who received modern EBRT (intensity-modulated radiotherapy [IMRT] or stereotactic body radiotherapy [SBRT]). At a median follow-up of 60 (2–177) months, actuarial 5-year biochemical failure-free survival rates were 97.8 and 91.8% (p = 0.017), respectively. The frequency of clinical failure in the HRLG group was less than that in the HRHG group (0% vs 5.4%, p = 0.012). The HRLG group had a better 5-year distant metastasis-free survival than the HRHG group (100% vs 96.0%, p = 0.035). As the HRLG group exhibited no clinical failure and better outcomes than the HRHG group, the HRLG group might potentially be classified as a lower-risk group.

Abstract Unresectable, isolated lymph node recurrence after radiotherapy is rare but a candidate for re-irradiation. However, severe toxicity is anticipated. Therefore, this study aimed to explore the efficacy and toxicity of re-irradiation in isolated lymph node recurrence of head and neck lesions. We analyzed 46 patients who received re-irradiation for lymph node recurrence without local progression. The primary tumor sites included the oral cavity in 17 patients, the hypopharynx in 12, the oropharynx in seven, the larynx in three, the nasopharynx in two, and other sites. During a median follow-up time of 10 months, the median survival time was 10.6 months, and the 1-year overall survival rate was 45.5%. The 1-year local control and progression-free survival rates were 49.8% and 39.3%, respectively. According to univariate analysis, age (≥ 65 years), the interval between treatment (≥ 12 months), rN category (rN1), and gross tumor volume (GTV

Abstract SpaceOAR, a polyethylene-glycol hydrogel, reduces rectal radiation exposure during radiation therapy for prostate cancer. Previously, our group reported the modified technique of hydrogel insertion, which achieves greater separated distance at prostate-apex. This study aimed to investigate the impact of separated distance at prostate-apex and our modifier technique, on radiation exposure reduction during proton beam therapy (PBT). We included 330 patients undergoing PBT with the relative biological effectiveness (RBE) of 63 Gray (Gy) for localized prostate cancer, and categorized them into groups 0 (no spacer, n = 141), 1 (separated distance of spacer at the prostate-apex level

Abstract This study aimed to examine the efficacy and toxicity of reirradiation in patients with locally recurrent oral, pharyngeal, and laryngeal cancers. We conducted a retrospective, multi-institutional analysis of 129 patients with previously irradiated cancer. The most frequent primary sites were the nasopharynx (43.4%), oral cavity (24.8%), and oropharynx (18.6%). With a median follow-up duration of 10.6 months, the median overall survival was 14.4 months and the 2-year overall survival rate was 40.6%. For each primary site, the 2-year overall survival rates were 32.1%, 34.6%, 30%, 60.8%, and 5.7% for the hypopharynx, oral cavity, larynx, nasopharynx, and oropharynx, respectively. Prognostic factors for overall survival were primary site (nasopharynx versus other sites) and gross tumor volume (GTV) (≤ 25 cm3 versus > 25 cm3). The 2-year local control rate was 41.2%. Twenty-four patients (18.6%) presented with grade ≥ 3 toxicities, including nine with hemorrhages that led to grade 5 toxicities in seven patients. All nine tumors that caused hemorrhage showed tumor encasement of the carotid ≥ 180 degrees and eight of nine tumors had larger GTV > 25 cm3. Reirradiation is a feasible treatment option for small local recurrence of oral, pharyngeal, and laryngeal cancers, with the requirement of a strict eligibility assessment for large tumors with carotid encasement.

Abstract Background Esophagectomy is the standard adjuvant treatment for superficial esophageal squamous cell carcinoma (SESCC) following noncurative endoscopic submucosal dissection (ESD). However, recent reports have also shown that ESD with adjuvant chemoradiotherapy (CRT) has promising results. This retrospective study aimed to elucidate the efficacy of CRT compared to surgery in patients with SESCC after noncurative ESD. Methods This study retrospectively compared the long-term outcomes of patients who received adjuvant treatment with surgery or CRT after noncurative ESD for SESCC. Results Data were collected from 60 patients who developed SESCC after noncurative ESD, 34 of whom received adjuvant chemoradiotherapy (CRT) and 26 underwent esophagectomy. The median follow-up periods were 46 and 56 months in the CRT and esophagectomy groups, respectively. The median patient age was significantly higher in the CRT group than in the esophagectomy group (69 vs. 65 years, p = 0.0054). CRT was completed in all patients, and the incidence of grade ≥ 3 nonhematologic adverse events was 6%. The overall and disease-free survival did not significantly differ between the two groups. Conclusions CRT following ESD seems a promising nonsurgical strategy for optimizing the selection of therapies for high-risk SESCC and warrant further investigation.

Background and purpose: To examine the role of proton beam therapy (PBT) in the treatment of extrahepatic biliary tract cancer (EBC). Methods and materials: We analyzed the data accumulated in the Proton-Net database, which prospectively registered all individual patient data treated with PBT in all Japanese proton institutions from May 2016 to June 2019. The primary endpoint was overall survival (OS), and the secondary endpoints were local control (LC), progression-free survival (PFS), and toxicity. Results: Ninety-three patients with unresectable and/or recurrent EBC were treated with PBT using a median prescribed dose of 67.5 Gy (RBE) (range, 50–72.6 Gy) in 25 (22–30 fractions). With a median follow-up of 16.3 months, the median survival time was 20.1 months and the 2-year OS was 37.8%. Two-year PFS and LC rates were 20.6% and 66.5%, respectively. Poor liver function (Child-Pugh B, C), a narrower distance between the tumor and digestive tract (2 cm >), and a larger tumor diameter (2 cm

Abstract To compare gastrointestinal (GI) and genitourinary (GU) toxicities in patients with localized prostate cancer treated with ultrahypofractionated radiotherapy (UHF) or brachytherapy [BT; low dose rate, LDR or high dose rate (HDR) with or without external beam radiotherapy (EBRT)]. We compared 253 UHF and 1664 BT ± EBRT groups. The main outcomes were the incidence and severity of acute and late GU and GI toxicities. The secondary endpoint was biochemical control rate. Cumulative late actuarial GU toxicity did not differ for grade ≥ 2 (8.6% at 5-years in UHF and 13.3% in BT ± EBRT, hazard ratio [HR], 0.7066; 95% CI, 0.4093–1.22, p = 0.2127). Actuarial grade ≥ 2 late GI toxicity was higher in UHF (5.8% at 5-years, HR: 3.619; 95% CI, 1.774–7.383, p

Abstract As several recent researches focus on the importance of Gleason 9–10, we examine the role of radiotherapy dose escalation in those patients. We analyzed 476 patients with Gleason score 9–10 prostate cancer treated with radiotherapy. Of them, 127 patients were treated with conventional-dose external beam radiotherapy (Conv RT) and 349 patients were treated with high-dose radiotherapy (HDRT; 249 patients received high-dose-rate brachytherapy boost + external beam radiotherapy [HDR boost] and 100 patients received intensity-modulated radiotherapy [IMRT]). We compared these treatment groups using multi-institutional retrospective data. The patients had a median follow-up period of 66.3 months. HDRT showed superior biochemical disease-free survival (bDFS) rate (85.2%; HDR boost 84.7% and IMRT 86.6%) to Conv RT (71.1%, p

Prostate squamous cell carcinoma (pSCC) rarely develops as a secondary cancer after treatment with low-dose-rate brachytherapy (LDR-BT). There is no established effective treatment for the disease condition. Herein, we present a 78-year-old man who developed pSCC 8 years after LDR-BT. He was subsequently selected to receive a combined multimodal treatment with high-dose-rate interstitial brachytherapy (HDR-ISBT), external beam radiation therapy, and chemotherapy for his pSCC. Eleven months later, he displayed no biochemical failure nor clinical radiographic recurrence. However, MRI detected a newly developed prostatic-rectal fistula (grade 4), and a colostomy was performed to relieve pain and inflammation. To our knowledge, this is the first report to perform a combined multimodal treatment with HDR-ISBT for pSCC suspected as a secondary cancer due to LDR-BT.

Abstract To compare the outcomes of localized prostate cancer treatment with high-dose-rate brachytherapy (HDR-BT) and low-dose-rate brachytherapy (LDR-BT), we examined 924 patients treated with HDR-BT + external beam radiotherapy (EBRT) and 500 patients treated with LDR-BT ± EBRT using multi-institutional retrospective data. The HDR-BT treated advanced disease with more hormonal therapy than LDR-BT. To reduce background selection bias, we performed inverse probability of treatment weighting (IPTW) analysis using propensity scores and excluded patients with T3b-4 disease/ initial prostate-specific antigen (PSA) levels > 50 ng/ml. The actuarial 5-year biochemical control rates (5y-bNED) were 96.3% and 95.7% in the HDR-BT and LDR-BT groups, respectively. The corresponding values were 100% and 96.5% in the low-risk group; 97.4% and 97.1% in the intermediate-risk group (97.2% and 97% in the higher titer group and 97.5% and 94.6% in the lower titer group, respectively); and 95.7% and 94.9% in the selected high-risk group, respectively. IPTW correction indicated no significant difference among the groups. The 5y-bNED in the HDR-BT + EBRT, LDR-BT + EBRT, and LDR-BT alone groups were 96.3%, 95.5%, and 97%, respectively (P = 0.3011). The corresponding values were 97.4%, 94.7%, and 96.6% (P = 0.1004) in the intermediate-risk group (97.5%, 100%, and 94.5% in the lower titer group [P = 0.122] and 97.2%, 96.2%, and 100% [P = 0.664] in the higher titer group, respectively) and 95.7%, 95.5%, and 100% (P = 0.859) in the high-risk group, respectively. The HDR-BT group showed a lower incidence of acute grade ≥ 2 genitourinary toxicities; the incidence of other early and late grade ≥ 2 toxicities were similar between the HDR-BT and LDR-BT groups. Acute genitourinary toxicity predicted the occurrence of late genitourinary toxicity. EBRT increased the risk of grade ≥ 2 gastrointestinal toxicity. HDR-BT + EBRT is a good alternative to LDR-BT ± EBRT for low-, intermediate-, and selected high-risk patients.

Background and purpose: Elongation of life expectancy had led to marked increase in number of elderly patients with localized prostate cancer. However, the standard treatment for such patients is not well determined because of a high prevalence of comorbidities and slow growth of prostate cancer. The aim of this study is to examine the feasibility of radiotherapy for elderly patients aged ≥80 years. Materials and methods: We compared 96 patients aged ≥80 years and 2333 younger patients (aged 60–79 years) using multi-institutional data included cT1-T4N0M0 prostate cancer treated with 902 external beam radiotherapy (EBRT) and 1527 brachytherapy (BT). Results: The 5-year biochemical failure-free survival rate was similar between elderly ≥80 years and younger control (91.3% vs. 85.9%, p = 0.6171) (100%, 92.9%, 82.4% and 96.3%, 93.7%, 89% for low, intermediate and high risk group), and for the prostate cancer-specific survival rate (100% and 99.3%, p = 0.6171). The accumulated incidence of late gastrointestinal (GI) at 5 years was also similar between elderly and younger patients (3.5% vs. 2.5%, p = 0.6857). Brachytherapy improved biochemical control rate and reduced GI toxicity compared with EBRT, however, enhanced late genitourinary (GU) toxicity, especially in elderly patients. Elderly received brachytherapy showed highest rate of late GU toxicity grade ≥2 of 22.1% than the younger counterparts of 12.7% at 5 years, whereas younger patients treated with EBRT had 2.4% and elderly EBRT had 2.7% (p

High-dose-rate interstitial brachytherapy (HDR-ISBT) is widely used for the treatment of pelvic tumors. However, there are a few reports on complications of applicator implantation in HDR-ISBT. We describe a case of small bowel perforation caused by applicator implantation in an 82-year-old male patient with recurrence tumor in the pelvis treated with HDR-ISBT. Eventually, the patient underwent laparotomy and partial intestinal resection. We recognized the site where the applicator was inserted into a part of the tumor on the mucosal surface. Pathological examination confirmed that the tumor had infiltrated the small intestine directly and that the infiltrated part had reached the submucosa. This is the first published report about small bowel perforation caused by applicator implantation. In cases where intestinal infiltration of the tumor is suspected, HDR-ISBT should be performed with maximum caution.

Radiation therapy is considered an optimal partner for immunotherapies. Several pre-clinical studies have demonstrated that regression of distant metastases, at remote non-irradiated sites of the body, termed the “abscopal effect”, can be achieved by an appropriate timing and combination of radiation with immunotherapy. However, nearly all pre-clinical and clinical studies evaluating a combination of radiation and immunotherapies have used external beam radiation therapy. We present in this case report, the abscopal effect observed in a 30-year-old Japanese woman with metastatic renal cell carcinoma after the treatment with high-dose-rate interstitial brachytherapy combined with nivolumab. This is the first published report demonstrating an abscopal effect following brachytherapy for human malignancy. Our case indicates that immuno-oncology effects are not limited to external beam irradiation regimens as they can also be attained by brachytherapy.

Abstract Background Late cardiovascular disease-related adverse events are one of the most common causes of premature mortality among long-term survivors of childhood cancer. As it is difficult to reduce the heart dose with traditional anteroposterior–posteroanterior field whole lung irradiation for pulmonary metastasis, improved radiation techniques are highly desirable. We report a case treated with whole lung irradiation using volumetric modulated arc therapy. Case presentation A 3-year-old Japanese girl with pulmonary metastases of Wilms’ tumor received 12 Gy in 8 fractions of whole lung irradiation using volumetric modulated arc therapy. The treatment was well tolerated, and the course was completed as planned without any toxicity. We found statistically significant reduced volumetric modulated arc therapy irradiation doses to organs at risk relative to those of the standard anteroposterior–posteroanterior field technique. The mean heart dose was 8.5 Gy for volumetric modulated arc therapy and 12.3 Gy for the anteroposterior–posteroanterior field. The doses to liver and thyroid were also more favorable with volumetric modulated arc therapy than with the anteroposterior–posteroanterior field technique. We confirmed the dosimetric advantages of volumetric modulated arc therapy over anteroposterior–posteroanterior field in whole lung irradiation in terms of superior normal organ protection. Conclusions Effective heart sparing is possible for whole lung irradiation using volumetric modulated arc therapy. Large-scale studies using standardized procedures should be conducted to validate our results.

Purpose: Our purpose was to evaluate the efficacy of proton beam therapy (PBT) in patients with 1 to 3 pulmonary oligometastases from various primary cancers in Japan. Methods and Materials: This multi-institutional retrospective survey included 118 patients with 141 metastatic lung tumors from miscellaneous primary cancers, across 6 Japanese institutions, and involved the analyses of local progression-free rate (LPF), distant progression-free rate, progression-free survival rate, cause-specific survival rate, and overall survival rate (OS). Treatment-induced adverse effects of grade ≥2 were evaluated according to the Common Terminology Criteria for Adverse Events (version 4.0). Cox proportional hazards regression models were used in univariable analysis and multivariable analysis (MVA) for the identification of the prognostic factors of LPF and OS. Results: The median follow-up duration from the time of PBT was 25.5 months. The major primary disease sites included colorectal cancer (42.4%), lung cancer (11.9%), head and neck cancer (8.5%), and kidney cancer (8.5%). For years 1, 2, and 3, LPFs were 92.2%, 86.3%, and 78.4%; distant progression-free rates were 59.1%, 44.1%, and 34.0%; progression-free survival rates were 49.6%, 31.7%, and 24.2%; cause-specific survival rates were 83.4%, 72.5%, and 64.8%; and OS rates were 79.0%, 67.8%, and 59.6%, respectively. Eight patients developed acute adverse effects (grade ≥2). Ten patients developed radiation pneumonitis (grade 2) as a late adverse effect. None of the patients developed severe late toxicity (grade ≥3). Colorectal cancer as the primary disease was the only prognostic factor associated with LPF that remained independently significant in the MVAs performed using 3 sets of parameters (hazard ratio [HR], 3.31-4.76 in 3 MVA sets). In the MVA, the significant prognostic factors for OS were performance status (HR, 2.78; 95% confidence interval, 1.01-7.67) and total tumor volume (HR, 1.01; 95% confidence interval, 1.00-1.02). Conclusions: PBT provides promising outcomes for pulmonary oligometastasis with acceptable toxicities.

Penoscrotal extramammary Paget’s disease (EMPD) is a rare intraepithelial adenocarcinoma in older male patients, and no effective nonsurgical treatment strategies are currently available. The aim of this study was to report the usefulness of external radiotherapy (RT) for penoscrotal EMPD in an inoperable elderly patient. This report presents the treatment of an 89-year-old man with widespread penoscrotal EMPD. A multidisciplinary treatment team decided on radical RT. The patient received a radiation dose of 61.8 Gy in 30 fractions through electron and photon beams. His treatment tolerance was good, and no severe toxicity had been observed up the last follow-up. At 6.5 years after the RT, the patient showed no evidence of recurrence. Definitive RT resulted in excellent disease control and minimal toxicity; thus, it could be a promising nonsurgical therapeutic option for penoscrotal EMPD, even in extremely elderly individuals.

Abstract Background The standard treatment for superficial esophageal cancer (SEC) involving muscularis mucosal (T1a-MM) or submucosal (T1b) invasion has been the surgical resection of the esophagus. However, esophagectomy with extended lymph node dissection is highly invasive. Recent reports have shown that endoscopic submucosal dissection (ESD) followed by chemoradiotherapy (CRT) has promising results and might become a new therapeutic approach. This retrospective study aimed to elucidate the efficacy and safety of this new treatment. Methods Patients with clinical stage T1b tumor without apparent metastasis treated with ESD followed by CRT from 2014 to 2017 (the CRT group) were included. The outcomes on disease-free survival (DFS) of this group were compared with those of consecutive patients in a historical control group who underwent ESD followed by esophagectomy (the esophagectomy group) between 2008 and 2015. Results Of 32 patients analyzed, 16 were in the CRT group and 16 with similar stage cancer were in the esophagectomy group. Radiotherapy was completed in all patients, and the incidence of grade ≥ 3 nonhematologic adverse events was 6%. The 2-year overall survival rates were 100%, and locoregional control was achieved in all patients in the CRT group, and the 2-year DFS rates were 88 and 100% for the CRT and esophagectomy groups, respectively, without significant differences. Conclusions Our data confirmed our new approach as being safe and effective for locoregional control and may provide a nonsurgical treatment option for patients with clinical stage T1b tumors.

Differentiated thyroid carcinoma is an uncommon malignancy of childhood and adolescence that is unique because it has an overall favorable prognosis despite its relatively high rate of nodal and distant metastases. Total thyroidectomy and positive 131I therapy are recommended for cases with pulmonary metastases. In contrast, anaplastic thyroid cancer is one of the most aggressive malignancies that have an unfavorable and miserable prognosis. We report a case with an impressively long history. The patient had multiple pulmonary metastases that had been diagnosed by 131I administration when he was 14 years old, about 45 years before he underwent thyroidectomy. He had been kept unaware of his disease by his family and received no treatment for most of his life. Pulmonary nodules were noted at several medical checkups and showed a remarkable decrease in size during the untreated 44-year period after the 131I administration. At age 58, his thyroid cancer was first detected and total thyroidectomy was performed, with subsequent radioiodine therapy for pulmonary metastases. Unfortunately, anaplastic carcinoma developed and he died of disseminated tumors later.

Purpose : We report our study on two patients to highlight the risk of underdosage of the clinical target volume (CTV) due to edema during high-dose-rate interstitial brachytherapy (HDR-ISBT) of mobile tongue cancer. Material and methods : To treat the lateral side of the CTV, flexible applicator tubes were implanted on the mouth floor. Two-dimensional planning was performed using X-ray images for Case 1, and three-dimensional (3D) planning was performed using computed tomography (CT) for Case 2. Prescribed doses for both cases were 54 Gy in nine fractions. Case reports : Case 1 was treated for cancer of the right lateral border of the tongue in 2005. Tongue edema occurred after implantation, and part of the lateral border of the tongue protruded between the applicator tubes. Acute mucosal reaction abated in the protruded area earlier than in the other parts of the CTV. In this case, the tumor recurred in this area 5 months after the treatment. Case 2 was treated for cancer of the left lateral border of the tongue. Because tongue edema occurred in this case also, plastic splints were inserted between the applicator tubes to push the edematous region into the irradiated area. The mucosal surface of the CTV was covered by the 70% isodose, and 100% isodose line for before and after splint insertion. Local control of the tumor was achieved 4 years after treatment. Discussion and conclusions : To ensure sufficient target coverage, 3D image-based planning using CT should be performed, followed by re-planning using repeated CT as needed. Also, the development of devices to prevent protrusion of the edematous tissue outside the target area will help to ensure the full dosing of CTV.

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Advances in fluorescence microscopy and tissue-clearing have revolutionised 3D imaging of fluorescently labelled tissues, organs and embryos. However, the complexity and high cost of existing software and computing solutions limit their widespread adoption, especially by researchers with limited resources. Here, we present Acto3D, an open-source software, designed to streamline the generation and analysis of high-resolution 3D images of targets labelled with multiple fluorescent probes. Acto3D provides an intuitive interface for easy 3D data import and visualisation. Although Acto3D offers straightforward 3D viewing, it performs all computations explicitly, giving users detailed control over the displayed images. Leveraging an integrated graphics processing unit, Acto3D deploys all pixel data to system memory, reducing visualisation latency. This approach facilitates accurate image reconstruction and efficient data processing in 3D, eliminating the need for expensive highperformance computers and dedicated graphics processing units. We have also introduced a method for efficiently extracting lumen structures in 3D. We have validated Acto3D by imaging mouse embryonic structures and by performing 3D reconstruction of pharyngeal arch arteries while preserving fluorescence information. Acto3D is a cost-effective and efficient platform for biological research. [ABSTRACT FROM AUTHOR]