Clinical outcomes and factors involved in the local control of proton beam therapy for oligometastatic liver tumors in patients with colorectal cancer.

BACKGROUND AND PURPOSE: There are no existing reports on proton beam therapy (PBT) for local control (LC) of liver metastasis of colorectal cancer (LMCRC). We calculated the LC rate of PBT for LMCRC and explored the influence of each factor on the LC rate. MATERIALS AND METHODS: Cases in which PBT was performed at our center between 2009 and 2018 were retrospectively selected from the database. Patients with LMCRC without extrahepatic lesions and no more than three liver metastases were included. Effectiveness was assessed based on LC, overall survival (OS), and progression-free survival (PFS) rates. Adverse events (AEs) are described. Factors that may be related to LC were also investigated. RESULTS: This study included 23 men and 18 women, with a median age of 66 (range 24-87) years. A total of 63 lesions were included in the study. The most frequent dose was 72.6 Gy (relative biological effectiveness)/22 fractions. The median follow-up period was 27.6 months. The 3­year LC, OS, and PFS rates were 54.9%, 61.6%, and 16.7%, respectively. Our multivariate analysis identified the distance between the tumor and the gastrointestinal (GI) tract as a factor associated with LC (P = 0.02). No grade ≥ 3 AEs were observed. None of the patients experienced liver failure during the acute or late phase. CONCLUSION: Care must be taken with tumors that have reduced planning target volume coverage owing to organs at risk restrictions, especially in tumors near the GI tract.

Safety of hydrogel spacers for rectal wall protection in patients with prostate cancer: A retrospective analysis of 200 consecutive cases.

OBJECTIVE: To evaluate the safety and complications of hydrogel spacer implantation. METHODS: This single-center historical cohort study retrospectively analyzed cases of hydrogel spacer implantation between October 2018 and March 2022. The survey items were the rates of possible hydrogel injection implementation, the success rate of hydrogel implantation including asymmetry, higher position, rectal wall infiltration, subcapsular injection, and other adverse events, and width created by the spacer. To investigate the learning curve, 1, 2, and 3 points were assigned to adverse event grades G1, G2, and G3, respectively. Spacer effectiveness obstruction, such as asymmetry was assigned 3 points. A Mann-Whitney U test was performed to assess statistically significant differences. RESULTS: The study included a total of 200 patients with a median (range) age of 70 (44-85) years. In 10 (5%) patients, hydrogel injection implementation was not possible. Of 190 patients who underwent hydrogel spacer placement, 168 (88%) received a satisfactory placement. The median (range) width of hydrogel spacers was 13.1 (4.4-18.7) mm. Spacer asymmetry, higher position, rectal wall infiltration, and prostate subcapsular infiltration occurred in 7 (3.7%), 5 (2.6%), 12 (6.3%), and 1 (0.5%) patients, respectively. G1 and G3 adverse events occurred in 13 (7%) and 4 (2%) patients, respectively. Practitioner #1 who performed the highest number of procedures had significantly (p = 0.04) lower total scores in group B. CONCLUSION: Spacer implantation yielded favorable outcomes with a high percentage of appropriate spacer implantation, and few major complications.

Identification of characteristic subepithelial surface granulomatosis in immune-related adverse event-associated enterocolitis.

Immune checkpoint inhibitors (ICIs) have provided an additional treatment option for various types of human cancers. However, ICIs often induce various immune-related adverse events (irAEs). Enterocolitis is a major irAE with poorly understood histopathological characteristics. In this study, we retrospectively investigated the histopathology of colon tissue samples from 17 patients treated with ICIs. There were two major histological patterns of colitis: an ulcerative colitis-like pattern and a graft vs host disease-like pattern. Although these two patterns of colitis were mutually exclusive, both patterns often showed a characteristic that we call "subepithelial surface granulomatosis" (SSG), which has not been reported in other types of colitis. SSG was found even in colon tissue without symptoms or endoscopic findings of colitis. Given the increasing reports of sarcoid reaction or exacerbation of tuberculosis after treatment with ICIs, granuloma formation could be a histological hallmark of systemic immune activation by ICIs. Although statistical significance was not obtained, probably because of the small sample size, SSG may be a surrogate biomarker of systemic anticancer immune activation. We propose that a prospective study with larger sample size be performed.

New femoral remains of Nacholapithecus kerioi: Implications for intraspecific variation and Miocene hominoid evolution.

The middle Miocene stem kenyapithecine Nacholapithecus kerioi (16-15 Ma; Nachola, Kenya) is represented by a large number of isolated fossil remains and one of the most complete skeletons in the hominoid fossil record (KNM-BG 35250). Multiple fieldwork seasons performed by Japanese-Kenyan teams during the last part of the 20th century resulted in the discovery of a large sample of Nacholapithecus fossils. Here, we describe the new femoral remains of Nacholapithecus. In well-preserved specimens, we evaluate sex differences and within-species variation using both qualitative and quantitative traits. We use these data to determine whether these specimens are morphologically similar to the species holotype KNM-BG 35250 (which shows some plastic deformation) and to compare Nacholapithecus with other Miocene hominoids and extant anthropoids to evaluate the distinctiveness of its femur. The new fossil evidence reaffirms previously reported descriptions of some distal femoral traits, namely the morphology of the patellar groove. However, results also show that relative femoral head size in Nacholapithecus is smaller, relative neck length is longer, and neck-shaft angle is lower than previously reported for KNM-BG 35250. These traits have a strong functional signal related to the hip joint kinematics, suggesting that the morphology of the proximal femur in Nacholapithecus might be functionally related to quadrupedal-like behaviors instead of more derived antipronograde locomotor modes. Results further demonstrate that other African Miocene apes (with the exception of Turkanapithecus kalakolensis) generally fall within the Nacholapithecus range of variation, whose overall femoral shape resembles that of Ekembo spp. and Equatorius africanus. Our results accord with the previously inferred locomotor repertoire of Nacholapithecus, indicating a combination of generalized arboreal quadrupedalism combined with other antipronograde behaviors (e.g., vertical climbing).

The effectiveness of proton beam therapy for liver metastatic recurrence in gastric cancer patients.

OBJECTIVE: The purpose of this cross-sectional study was to evaluate the efficacy and safety of proton beam therapy for liver metastatic recurrence in gastric cancer patients. METHODS: Consecutive patients who underwent proton beam therapy from 2010 to 2015 were isolated from our institutional database. Patients with extrahepatic metastatic lesions were excluded. Seven patients were enrolled. The median diameter of target lesions was 31 mm (13-68 mm). The most frequent dosage was 72.6 Gy equivalent in 22 fractions. The effectiveness was assessed based on the local control, overall survival and progression-free survival rates. The local control, overall survival and progression-free survival rates were calculated using the Kaplan-Meier method. Adverse events were described according to the patients' medical records. RESULTS: The median follow-up period was 41.7 months (20.7-66.3 months). The 3-year local control, overall survival and progression-free survival rates were 85.7, 68.6 and 43%, respectively. All patients completed proton beam therapy without interruption. No grade ≥3 adverse events were observed. CONCLUSIONS: Proton beam therapy might be a treatment option for patients with liver metastasis of gastric cancer.

Multivariate analysis of variations in intrinsic foot musculature among hominoids.

Comparative analysis of the foot muscle architecture among extant great apes is important for understanding the evolution of the human foot and, hence, human habitual bipedal walking. However, to our knowledge, there is no previous report of a quantitative comparison of hominoid intrinsic foot muscle dimensions. In the present study, we quantitatively compared muscle dimensions of the hominoid foot by means of multivariate analysis. The foot muscle mass and physiological cross-sectional area (PCSA) of five chimpanzees, one bonobo, two gorillas, and six orangutans were obtained by our own dissections, and those of humans were taken from published accounts. The muscle mass and PCSA were respectively divided by the total mass and total PCSA of the intrinsic muscles of the entire foot for normalization. Variations in muscle architecture among human and extant great apes were quantified based on principal component analysis. Our results demonstrated that the muscle architecture of the orangutan was the most distinctive, having a larger first dorsal interosseous muscle and smaller abductor hallucis brevis muscle. On the other hand, the gorilla was found to be unique in having a larger abductor digiti minimi muscle. Humans were distinguished from extant great apes by a larger quadratus plantae muscle. The chimpanzee and the bonobo appeared to have very similar muscle architecture, with an intermediate position between the human and the orangutan. These differences (or similarities) in architecture of the intrinsic foot muscles among humans and great apes correspond well to the differences in phylogeny, positional behavior, and locomotion.

Sexual dimorphism of body size in an African fossil ape, Nacholapithecus kerioi.

Sexual size dimorphism in the African fossil ape Proconsul nyanzae (18 million years ago, 18 Ma) has been previously documented. However, additional evidence for sexual dimorphism in Miocene hominoids can provide great insight into the history of extant hominoid mating systems. The present study focused on body mass (BM) sexual dimorphism in Nacholapithecus kerioi from the Middle Miocene (16-15 Ma) in Africa. Bootstrap analysis revealed that P. nyanzae BM sexual dimorphism was lower than that in Pan troglodytes, which exhibits moderate sexual dimorphism, as reported previously. The same simulation revealed that BM sexual dimorphism of N. kerioi was comparable with that in Gorilla spp.; i.e., the males were approximately twice as large as the females. High sexual dimorphism in extant apes is usually indicative of a polygynous social structure (gorilla) or solitary/fission-fusion social system (orangutan). However, because of the high proportion of adult males in this fossil assemblage, the magnitude of dimorphism inferred here cannot be associated with a gorilla-like polygynous or oranguran-like solitary/fission-fusion social structure, and may reflect either taphonomic bias, or some other social structure. Extant hominoids have a long evolutionary history owing to their deep branching, comprising only a few existing members of the original highly successful group. Therefore, it is not surprising that the mating systems of extant hominoids fail to provide fossil apes with a perfect "model". The mating systems of extinct hominoids may have been more diverse than those of extant apes.

Proton beam therapy for bone sarcomas of the skull base and spine: A retrospective nationwide multicenter study in Japan.

We conducted a retrospective, nationwide multicenter study to evaluate the clinical outcomes of proton beam therapy for bone sarcomas of the skull base and spine in Japan. Eligibility criteria included: (i) histologically proven bone sarcomas of the skull base or spine; (ii) no metastases; (iii) ≥20 years of age; and (iv) no prior treatment with radiotherapy. Of the 103 patients treated between January 2004 and January 2012, we retrospectively analyzed data from 96 patients who were followed-up for >6 months or had died within 6 months. Seventy-two patients (75.0%) had chordoma, 20 patients (20.8%) had chondrosarcoma, and four patients (7.2%) had osteosarcoma. The most frequent tumor locations included the skull base in 68 patients (70.8%) and the sacral spine in 13 patients (13.5%). Patients received a median total dose of 70.0 Gy (relative biological effectiveness). The median follow-up was 52.6 (range, 6.3-131.9) months. The 5-year overall survival, progression-free survival, and local control rates were 75.3%, 49.6%, and 71.1%, respectively. Performance status was a significant factor for overall survival and progression-free survival, whilst sex was a significant factor for local control. Acute Grade 3 and late toxicities of ≥Grade 3 were observed in nine patients (9.4%) each (late Grade 4 toxicities [n = 3 patients; 3.1%]). No treatment-related deaths occurred. Proton beam therapy is safe and effective for the treatment of bone sarcomas of the skull base and spine in Japan. However, larger prospective studies with a longer follow-up are warranted.

Clinical results of proton beam therapy for hepatocellular carcinoma over 5 cm.

AIM: This study aimed to evaluate the safety and efficacy of proton beam therapy for large hepatocellular carcinoma (HCC). METHODS: Twenty-four patients with a HCC larger than 5.0 cm were treated with proton beam therapy at our institution between 2008 and 2015. RESULTS: The clinical stage was I in 2 patients, II in 9 patients, and IIIB in 13 patients. Ten of the 24 patients were not surgical candidates because of advanced HCC or old age. Median tumor size was 90 mm (range, 50-180 mm). Median total dose delivered was 72.6 Gray-equivalents (GyE) in 22 fractions (range, 60.8-85.8 GyE). Median follow-up period was 17.5 months (range, 3-70 months). Local control rate at 2 years was 87.0%. The 2-year overall survival rate was 52.4%. The predominant tumor progression pattern was new hepatic tumor development outside the irradiated field. No acute or late treatment-related toxicity of grade 3 or higher, other than dermatitis, was observed. CONCLUSIONS: These results show that proton beam therapy offers an effective and safe method for treating patients with large HCC. Proton beam therapy represents a promising method for treatment of large-volume HCC.

High Dose Hypofractionated Proton Beam Therapy is a Safe and Feasible Treatment for Central Lung Cancer.

BACKGROUND: There have been few reports about high total dose hypofractionated proton beam therapy for central lung cancer. The aim of this study was to examine retrospectively the safety and efficacy of high total dose hypofractionated proton beam therapy for central lung cancer. PATIENTS AND METHODS: Patients treated by proton beam therapy for central lung cancer located less than 2 cm from the trachea, mainstem bronchus, or lobe bronchus were included in this study. All patients received 80 Gy of relative biological dose effectiveness (RBE) in 25 fractions with proton beam therapy over 5 weeks between January 2009 and February 2015. The toxicities were evaluated using the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer criteria. RESULTS: Twenty patients, including 14 clinically inoperable patients (70%), received proton beam therapy for central lung cancer. The median patient age was 75 years (range: 63-90 years), the median follow up time was 27.5 months (range: 12-72 months), and the median tumor diameter was 39.5 mm (range: 24-81 mm). All patients were followed for at least 20 months or until death. The 2-year overall survival rate was 73.8% (100% in operable patients, and 62.5% in inoperable patients), and the 2-year local control rate was 78.5%. There was no Grade 3 or higher toxicities, including bronchial stricture, obstruction, and fistula. CONCLUSIONS: The present study suggests that a high total dose hypofractionated proton beam therapy for central lung cancer was safe and feasible.

Sacral vertebral remains of the Middle Miocene hominoid Nacholapithecus kerioi from northern Kenya.

This study describes two new sacral specimens of Nacholapithecus kerioi, KNM-BG 42753I and KNM-BG 47687A, from the Aka Aiteputh Formation in Nachola, northern Kenya, excavated in 2002. They are of roughly equal size and are considered to belong to males. When scaled by body mass, the lumbosacral articular surface area of the better preserved specimen, KNM-BG 42753I, is smaller than that in Old World monkeys but similar to that in extant great apes and New World monkeys, as well as Proconsul nyanzae. The relatively narrow dimensions of the first sacral vertebral body in the transverse and sagittal planes are characteristics of N. kerioi and P. nyanzae and similar to those of extant great apes. In N. kerioi, lumbosacral surface area relative to body mass is small. This may simply be an extension of a trend from the previously reported small thoracolumbar vertebrae to the sacrum. ​The first sacral vertebrae of N. kerioi and Epipliopithecus vindobonensis have a higher craniocaudal vertebral body reduction (CVR; a higher CVR indicates a wider cranial width relative to a narrower caudal width), similar to that in Old World monkeys. Old World monkeys have a higher CVR, and usually have three sacral vertebrae, fewer than seen in extant great apes, which have a lower CVR and four to six (sometimes as many as eight) sacral vertebrae. New World monkeys have a lower CVR than Old World monkeys, but generally possess only three sacral vertebrae, and have a large caudal articular surface, which may be related, at least in the Atelidae, to the grasping ability of their tails. The possibility that N. kerioi had only three sacral vertebrae cannot be ruled out, because E. vindobonensis and Old World monkeys, with higher CVRs, have sacra consisting of three sacral vertebrae.

Preliminary results of proton beam therapy combined with weekly cisplatin intra-arterial infusion via a superficial temporal artery for treatment of maxillary sinus carcinoma.

OBJECTIVE: This study aimed to evaluate the efficacy and toxicity of proton beam therapy combined with cisplatin intra-arterial infusion via a superficial temporal artery as treatment for maxillary sinus carcinoma. METHODS: Twenty-six patients with confirmed maxillary sinus carcinoma were enrolled in this study from May 2009 to April 2011. Patients underwent proton beam therapy and intra-arterial infusion chemotherapy with cisplatin. RESULTS: The median total dose was 70.4 GyE per 32 fractions, and the median dose of cisplatin was 300 mg/body for six cycles of intra-arterial infusion. The 3-year overall survival rate was 58% for all patients (n = 26), 58% for patients with stage T4 disease (n = 12), 57% for patients with

Carpal bones of Nacholapithecus kerioi, a Middle Miocene Hominoid From Northern Kenya.

OBJECTIVES: The carpal bones of the middle Miocene hominoid Nacholapithecus kerioi are described based on new materials. MATERIALS AND METHODS: The materials comprise a trapezoid, three capitates, two hamates, a centrale, a lunate, a triquetrum, and a pisiform, collected during the 2001 and 2002 field seasons from Nachola, Kenya. We also describe a pisiform recently assigned to the type specimen of N. kerioi, KNM-BG 35250. RESULTS: In the Nacholapithecus wrist, the ulnar styloid process articulates with both the triquetrum and pisiform, and the triquetrum facet on the hamate is relatively proximodistally oriented in dorsal view. The Nacholapithecus capitate possesses a moderate distopalmar hook-like process and separated radial articular facets for the trapezoid and the second metacarpal due to the carpometacarpal ligament attachment that is absent in the Proconsul capitate. DISCUSSION: The carpal anatomy of Nacholapithecus is similar to that of the early Miocene hominoid Proconsul. However, Nacholapithecus wrist anatomy appears to exhibit slightly more emphasized stability. Am J Phys Anthropol 160:469-482, 2016. © 2016 Wiley Periodicals, Inc.

Dosemetric Parameters Predictive of Rib Fractures after Proton Beam Therapy for Early-Stage Lung Cancer.

Proton beam therapy (PBT) is the preferred modality for early-stage lung cancer. Compared with X-ray therapy, PBT offers good dose concentration as revealed by the characteristics of the Bragg peak. Rib fractures (RFs) after PBT lead to decreased quality of life for patients. However, the incidence of and the risk factors for RFs after PBT have not yet been clarified. We therefore explored the relationship between irradiated rib volume and RFs after PBT for early-stage lung cancer. The purpose of this study was to investigate the incidence and the risk factors for RFs following PBT for early-stage lung cancer. We investigated 52 early-stage lung cancer patients and analyzed a total of 215 irradiated ribs after PBT. Grade 2 RFs occurred in 12 patients (20 ribs); these RFs were symptomatic without displacement. No patient experienced more severe RFs. The median time to grade 2 RFs development was 17 months (range: 9-29 months). The three-year incidence of grade 2 RFs was 30.2%. According to the analysis comparing radiation dose and rib volume using receiver operating characteristic curves, we demonstrated that the volume of ribs receiving more than 120 Gy3 (relative biological effectiveness (RBE)) was more than 3.7 cm(3) at an area under the curve of 0.81, which increased the incidence of RFs after PBT (P < 0.001). In this study, RFs were frequently observed following PBT for early-stage lung cancer. We demonstrated that the volume of ribs receiving more than 120 Gy3 (RBE) was the most significant parameter for predicting RFs.

Morphology of the thoracolumbar spine of the middle Miocene hominoid Nacholapithecus kerioi from northern Kenya.

A new caudal thoracic and a new lumbar vertebra of Nacholapithecus kerioi, a middle Miocene hominoid from northern Kenya, are reported. The caudal thoracic vertebral body of N. kerioi has a rounded median ventral keel and its lateral sides are moderately concave. The lumbar vertebral body has an obvious median ventral keel. Based on a comparison of vertebral body cranial articular surface size between the caudal thoracic vertebrae in the present study and one discussed in a previous study (KNM-BG 35250BO, a diaphragmatic vertebra), N. kerioi has at least two post-diaphragmatic vertebrae (rib-bearing lumbar-type thoracic vertebrae), unlike extant hominoids. It also has thick, rounded, and moderately long metapophyses on the lumbar vertebra that project dorsolaterally. The spinous process bases of its caudal thoracic and lumbar vertebrae originate caudally between the postzygapophyses, as described previously in the KNM-BG 35250 holotype specimen. In other words, the postzygapophyses of N. kerioi do not project below the caudal border of the spinous processes, similar to those of extant great apes, and unlike small apes and monkeys, which have more caudally projecting postzygapophyses. Nacholapithecus kerioi has a craniocaudally expanded spinous process in relation to vertebral body length, also similar to extant great apes. Both these spinous process features of N. kerioi differ from those of Proconsul nyanzae. The caudal thoracic vertebra of N. kerioi has a caudally-directed spinous process, whose tip is tear-drop shaped. These features resemble those of extant apes. The morphology of the spinous process tips presumably helps vertebral stability by closely stacking adjacent spinous process tips as seen in extant hominoids. The morphology of the spinous process and postzygapophyses limits the intervertebral space and contributes to the stability of the functional lumbar region as seen in extant great apes, suggesting that antipronograde activity was included in the positional behavior of N. kerioi.

High-dose proton beam therapy for stage I non-small cell lung cancer: Clinical outcomes and prognostic factors.

BACKGROUND: Evidence has suggested that radiation therapy with a lower dose per fraction may be a reasonable option for the treatment of centrally located non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the safety and efficacy of two proton beam therapy (PBT) protocols for stage I NSCLC and to determine prognostic factors. MATERIAL AND METHODS: This study included patients clinically diagnosed with stage I NSCLC. Based on the location of the tumor, one of the two PBT protocols was administered. Patients with peripherally located tumors were given 66 Gy relative biological dose effectiveness (RBE) over 10 fractions (Protocol A) while patients with centrally located tumors were given 80 Gy (RBE) over 25 fractions (Protocol B). RESULTS: Between January 2009 and May 2012, 56 eligible patients were enrolled (protocol A: 32 patients; protocol B: 24 patients). The three-year overall survival (OS), progression-free survival (PFS), and local control (LC) rates were 81.3% [95% confidence interval (CI) 75.9-86.7%], 73.4% (95% CI 67.2-79.6%), and 96.0% (95% CI 93.2-98.8%), respectively. There were no significant differences in outcomes between the two protocols. Late grade 2 and 3 pulmonary toxicities were observed in nine patients (13.4%) and one patient (1.5%), respectively; no grade 4 or 5 toxicities were observed. Sex, age, performance status, T-stage, operability, and tumor pathology were not associated with OS and PFS. Only maximum standardized uptake value (SUVmax; <5 vs. ≥5) was identified as a significant prognostic factor for OS and PFS. CONCLUSION: Both high-dose PBT protocols achieved high LC rates with tolerable toxicities in stage I NSCLC patients, and SUVmax was a significant prognostic factor.

Quality of life after bilateral total knee arthroplasty determined by a 3-year longitudinal evaluation using the Japanese knee osteoarthritis measure.

BACKGROUND: Recently, the Japanese knee osteoarthritis measure (JKOM), a new disease-specific and patient-derived quality of life (QOL) measure, has been developed. The objectives of this study were to longitudinally evaluate QOL assessed by JKOM and objective outcomes including knee society score (KSS), range of motion (ROM), and timed up and go test (TUG) of patients who underwent bilateral total knee arthroplasties (TKAs) for osteoarthritis; to evaluate correlations between JKOM and those objective outcomes; and to test our hypothesis that increased maximum flexion leads to better JKOM. METHODS: Forty patients with bilateral TKAs and ≥ 3-year follow-up were included. There were 35 female and 5 male patients with a mean patient age of 74 years. They were evaluated preoperatively (Pre), 5-29 months after unilateral TKA (after U), 12-21 months after bilateral TKAs (1 year after B), 24-34 months after bilateral TKAs (2 years after B), and 36-46 months after bilateral TKAs (3 years after B) using JKOM, KSS, TUG, and ROM. RESULTS: Improvements in JKOM and TUG were statistically significant between "Pre" and "after U", and between the "after U" and "1 year after B". Improvements in the KSS function score were statistically significant between "after U" and "1 year after B" but not between "Pre" and "after U". The improvements in the JKOM scores, the KSS function score, and TUG did not increase after the 1-year follow-up but was maintained at "3 years after B". The maximum flexion value did not change among the evaluation time points. There were statistically significant correlations between JKOM with KSS and TUG but not with ROM. CONCLUSIONS: There were statistically significant correlations between JKOM with KSS and TUG but not with ROM. Therefore, our hypothesis was false even in a Japanese population.

Clinical results of proton beam therapy for twenty older patients with esophageal cancer.

BACKGROUND: In an aging society, increasing number of older patients are diagnosed with esophageal cancer. The purpose of this study was to assess the clinical efficacy and safety of proton beam therapy for older patients with esophageal cancer. PATIENTS AND METHODS: Older patients (age: ≥ 65 years) newly diagnosed with esophageal cancer between January 2009 and June 2013 were enrolled in this study. All patients underwent either proton beam therapy alone or proton beam therapy with initial X-ray irradiation. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Twenty patients were eligible for this study and all completed the treatment. The median age was 78 years (range: 65-89 years) and the median follow-up time was 26.5 months (range: 6-62 months). Seven patients had lymph node metastases and 10 had stage II/III cancer. The median dose of proton beam therapy was 72.6 Gy relative biological dose effectiveness (RBE) (range: 66-74.8 Gy [RBE]) for proton beam therapy alone and 33 Gy (RBE) (range: 30.8-39.6 Gy [RBE]; total dose range: 66.8-75.6 Gy [RBE]) for proton beam therapy with initial X-ray irradiation. The 2-year overall survival rate was 81.8% (95% confidence interval [CI]: 62.4%-100%), and the 2-year local control rate was 89.4% (95% CI: 75.5%-100%). Grade 2 or 3 toxicities occurred in some cases; however, no grade 4 or 5 toxicity was observed. CONCLUSIONS: High-dose (66-75.6 Gy [RBE]) proton beam therapy without chemotherapy was an efficacious and safe treatment for older patients with esophageal cancer.

Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study.

BACKGROUND: We aimed to examine whether stereotactic radiosurgery without whole-brain radiotherapy (WBRT) as the initial treatment for patients with five to ten brain metastases is non-inferior to that for patients with two to four brain metastases in terms of overall survival. METHODS: This prospective observational study enrolled patients with one to ten newly diagnosed brain metastases (largest tumour <10 mL in volume and <3 cm in longest diameter; total cumulative volume ≤15 mL) and a Karnofsky performance status score of 70 or higher from 23 facilities in Japan. Standard stereotactic radiosurgery procedures were used in all patients; tumour volumes smaller than 4 mL were irradiated with 22 Gy at the lesion periphery and those that were 4-10 mL with 20 Gy. The primary endpoint was overall survival, for which the non-inferiority margin for the comparison of outcomes in patients with two to four brain metastases with those of patients with five to ten brain metastases was set as the value of the upper 95% CI for a hazard ratio (HR) of 1·30, and all data were analysed by intention to treat. The study was finalised on Dec 31, 2012, for analysis of the primary endpoint; however, monitoring of stereotactic radiosurgery-induced complications and neurocognitive function assessment will continue for the censored subset until the end of 2014. This study is registered with the University Medical Information Network Clinical Trial Registry, number 000001812. FINDINGS: We enrolled 1194 eligible patients between March 1, 2009, and Feb 15, 2012. Median overall survival after stereotactic radiosurgery was 13·9 months [95% CI 12·0-15·6] in the 455 patients with one tumour, 10·8 months [9·4-12·4] in the 531 patients with two to four tumours, and 10·8 months [9·1-12·7] in the 208 patients with five to ten tumours. Overall survival did not differ between the patients with two to four tumours and those with five to ten (HR 0·97, 95% CI 0·81-1·18 [less than non-inferiority margin], p=0·78; pnon-inferiority<0·0001). Stereotactic radiosurgery-induced adverse events occurred in 101 (8%) patients; nine (2%) patients with one tumour had one or more grade 3-4 event compared with 13 (2%) patients with two to four tumours and six (3%) patients with five to ten tumours. The proportion of patients who had one or more treatment-related adverse event of any grade did not differ significantly between the two groups of patients with multiple tumours (50 [9%] patients with two to four tumours vs 18 [9%] with five to ten; p=0·89). Four patients died, mainly of complications relating to stereotactic radiosurgery (two with one tumour and one each in the other two groups). INTERPRETATION: Our results suggest that stereotactic radiosurgery without WBRT in patients with five to ten brain metastases is non-inferior to that in patients with two to four brain metastases. Considering the minimal invasiveness of stereotactic radiosurgery and the fewer side-effects than with WBRT, stereotactic radiosurgery might be a suitable alternative for patients with up to ten brain metastases. FUNDING: Japan Brain Foundation.

Preliminary Investigation of the Efficacy and Indications of Proton Beam Therapy for Stage IV Pancreatic Adenocarcinoma.

BACKGROUND: The present study aimed to evaluate proton beam therapy (PBT) for stage IV pancreatic adenocarcinoma and its metastases and define the criteria for eligibility. Materials and methods: We retrospectively evaluated the patients who had a histopathological diagnosis of pancreatic adenocarcinoma, had progressed to stage IV, and underwent PBT for both the primary and some metastatic lesions between 2017 and 2022. PBT was performed using the passive scattering technique. RESULTS: Sixteen patients (median age, 72 years; range, 55-85 years) were enrolled. All patients had stage IV pancreatic cancer at the initiation of PBT. The median duration from the date of stage IV diagnosis to the initiation of PBT was 5.8 (range, 0.4-13.5) months. Three patients had been diagnosed as having recurrent stage IV cancer at other institutions before their referral to our hospital because they had local recurrence and distant metastases after the resection of the primary tumor. Chemotherapy was as follows: pre-PBT, 0, 1, 2, and 3 lines in 4, 7, 4, and 1 patients, respectively; concurrent with PBT, 0 and 1 line in 11 and 5 patients, respectively; post-PBT, 0 and 1 line in 5 and 5 patients, respectively; and unknown, 6 patients. The median survival times (MSTs) from the date of stage IV diagnosis for the with or without non-irradiated active metastatic tumor were 11.4 and 20.1 months, respectively. Univariate analysis revealed that the performance status (PS) levels (p < 0.01), the carbohydrate antigen (CA) 19-9 tumor marker levels (p < 0.01), active tumors not treated with irradiation (p = 0.02), and with or without post-PBT chemotherapy (p < 0.01) were statistically significant factors. Multivariate analysis revealed that the CA 19-9 tumor marker levels (p= 0.04), the number of metastatic lesions (p = 0.049), and with or without non-irradiated active metastatic tumors (p = 0.02) were significant factors. CONCLUSION: PBT is indicated when the number of metastases is limited to ≤ 4 lesions and all tumors can be irradiated within the smallest possible number of irradiation fields that can be performed within the patient's tolerable time, which is a subjective duration that depends on the patient's reaction during each session. It may be a viable treatment option for patients with oligometastatic pancreatic cancer.