Analysis of respiratory-induced motion trajectories of individual liver segments in patients with hepatocellular carcinoma.

PURPOSE: To analyze the respiratory-induced motion trajectories of each liver segment for hepatocellular carcinoma (HCC) to derive a more accurate internal margin and optimize treatment protocol selection. MATERIALS AND METHODS: Ten-phase-gated four-dimensional computed tomography (4DCT) scans of 14 patients with HCC were analyzed. For each patient, eight representative regions of interest (ROI) were delineated on each liver segment in all 10 phases. The coordinates of the center of gravity of each ROI were obtained for each phase, and then the respiratory motion in the left-right (LR), anteroposterior (AP), and craniocaudal (CC) directions was analyzed. Two sets of motion in each direction were also compared in terms of only two extreme phases and all 10 phases. RESULTS: Motion of less than 5 mm was detected in 12 (86%) and 10 patients (71%) in the LR and AP directions, respectively, while none in the CC direction. Motion was largest in the CC direction with a maximal value of 19.5 mm, with significant differences between liver segment 7 (S7) and other segments: S1 (p < 0.036), S2 (p < 0.041), S3 (p < 0.016), S4 (p < 0.041), and S5 (p < 0.027). Of the 112 segments, hysteresis >1 mm was observed in 4 (4%), 2 (2%), and 15 (13%) in the LR, AP, and CC directions, respectively, with a maximal value of 5.0 mm in the CC direction. CONCLUSION: A significant amount of respiratory motion was detected in the CC direction, especially in S7, and S8. Despite the small effect of hysteresis, it can be observed specifically in the right lobe. Therefore, caution is required when using 4DCT to determine IM using only end-inspiration and end-expiration. Understanding the respiratory motion in individual liver segments can be helpful when selecting an appropriate treatment protocol.

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.

The additional diagnostic impact of positron emission tomography-computed tomography for lymph node metastasis from colorectal cancer: A prospective lymph node level analysis.

BACKGROUND: We conducted a prospective study to determine the diagnostic performance of positron emission tomography-computed tomography (PET-CT) for lymph node metastasis in colorectal cancer patients. METHODS: We enrolled patients scheduled to receive curative surgery with lymph node dissection for colorectal adenocarcinoma who underwent contrast-enhanced abdominopelvic CT and PET-CT before surgery and who had primary lesions of cT2 or deeper. A radiologist determined the fluorodeoxyglucose uptake and the standardized uptake value (SUV) and metabolic volume (MV) to diagnose metastasis in cases with enlarged lymph nodes (≥7 mm long in minor diameter) on contrast-enhanced CT. Two gastrointestinal surgeons intraoperatively identified target lymph nodes to assess the association between images and pathological findings. The diagnostic performance (i.e., sensitivity, specificity, and positive and negative predictive values) for lymph node metastasis was determined using multilevel logistic modeling. RESULTS: A total of 205 colorectal cancer patients were enrolled from February 2018 to April 2020 and 194 patients were analyzed in this study. The sensitivity, specificity, and positive and negative predictive values of PET-CT were 15.3% (13.4%-17.5%), 100.0% (99.0%-100.0%), 100.0% (51.2%-100.0%), and 98.7% (98.5%-99.0%), respectively. CONCLUSION: PET-CT is a useful modality for determining the presence of metastasis in swollen lymph nodes on contrast-enhanced CT in colorectal cancer patients.

The effects of intensive oral care before surgery for gastric cancer patients.

OBJECTIVES: Oral function management has been recognized as important strategy for preventing postoperative complications. In this historical cohort study, we focused on the patients who planed gastrectomy, and investigated the appropriate duration and frequency of preoperative oral care to prevent complications after surgery. METHODS: Patients who planed surgery for gastric cancer between 2012 and 2018 were enrolled. We defined intensive oral care (IOC) as initial intervention at least three weeks before surgery and follow-up intervention within a week before surgery. As the primary outcome, the incidence of postoperative infectious complications was compared between the IOC and non-intensive oral care groups. RESULTS: A total of 576 patients were enrolled, including 66 with IOC. The incidence of infectious complications was 2/66 (3.0%) in the IOC group and 64/510 (12.5%) in the non-intensive oral care group. After adjusting for confounding factors, patients with IOC exposure had a lower chance of developing postoperative infectious complications (odds ratio; 0.217, 0.051-0.927). CONCLUSIONS: Intensive oral care can help prevent postoperative infectious complications after gastrectomy. These findings suggest that appropriate preoperative oral care includes at least two interventions: three weeks or more before and within one week before surgery.

The impact of different setup methods on the dose distribution in proton therapy for hepatocellular carcinoma.

PURPOSE: To investigate the impact of different setup methods, vertebral body matching (VM), diaphragm matching (DM), and marker matching (MM), on the dose distribution in proton therapy (PT) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Thirty-eight HCC lesions were studied retrospectively to assess changes in the dose distribution on two computed tomography (CT) scans. One was for treatment planning (1st-CT), and the other was for dose confirmation acquired during the course of PT (2nd-CT). The dose coverage of the clinical target volume (CTV-D98 ) and normal liver volume that received 30 Gy relative biological effectiveness (RBE) (liver-V30 ) were evaluated under each condition. Initial treatment planning on the 1st-CT was defined as reference, and three dose distributions recalculated using VM, DM, and MM on the 2nd-CT, were compared to it, respectively. In addition, the relationship between the CTV-D98 of each method and the distance between the center of mass (COM) of the CTV and the right diaphragm top was evaluated. RESULTS: For CTV-D98 , significant differences were observed between the reference and VM and DM, respectively (P = 0.013, P = 0.015). There were also significant differences between MM and VM and DM, respectively (P = 0.018, P = 0.036). Regarding liver-V30 , there was no significant difference in any of the methods, and there were no discernable difference due to the different setup methods. In DM, only two out of 34 cases with a distance from right diaphragm top to COM of CTV of 90 mm or less that CTV-D98 difference was 5% or more and CTV-D98 was worse than VM were confirmed. CONCLUSION: Although MM is obviously the most effective method, it is suggested that DM may be particularly effective in cases where the distance from right diaphragm top to COM of CTV of 90 mm or less.

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.

Clinical impact of periodontal disease on postoperative complications in gastrointestinal cancer patients.

BACKGROUND: The effectiveness of perioperative oral management in gastrointestinal surgery remains unclear. To elucidate the clinical significance of oral care, we investigated the relationship between the oral environment and postoperative infectious complications (POICs) in patients undergoing gastrointestinal surgery. METHODS: This was a single-institute and historical cohort study of 341 patients. The participants were isolated from consecutive patients undergoing planned radical resection for gastrointestinal carcinoma from January 2016 to June 2017. Dentists assessed the oral environment for periodontal disease, hygiene status, dry mouth, fur on tongue, and tooth stumps. All patients received scaling and tooth brushing instructions. A stepwise logistic regression analysis was conducted to identify risk factors for POICs among the different oral statuses. RESULTS: The surgical procedures performed were gastrectomy in 123 (36.1%), colorectal resection in 185 (54.2%), and pancreatoduodenectomy or others in 38 (11.1%). POICs occurred in 48 patients (14.1%), including deep organ space infection in 20, surgical site infection in 11, anastomotic leakage in 5, urinary tract infection in 4, pneumonia in 2, and others in 6. After adjusting for confounding factors, periodontal disease was isolated as an independent risk factor for POICs (odds ratio 2.091, p = 0.037, 95% confidence interval 1.045-4.183). Other variables of oral environment such as hygiene status, dry mouth, fur on tongue, and tooth stumps did not have a significant impact on POICs. CONCLUSIONS: Periodontal disease is a risk factor for infectious complications after gastrointestinal surgery.

[Four Patients Who Underwent Proton Beam Therapy after Debulking Surgery and Omental Wrapping of the Residual Tumor as a Spacer for Unresectable Local Recurrence of Rectal Cancer].

We report 4 patients who underwent proton beam therapy after debulking surgery for unresectable local recurrence of rectal cancer. Case 1: A 55-year-old man underwent radiotherapy and systemic chemotherapy for local recurrence; however, the lesion exhibited evident regrowth. Combination therapy of debulking surgery, omental wrapping of the residual tumor as a spacer, and postoperative proton beam therapy was performed. He died of lung metastasis after 24 months. Case 2: A 79- year-old woman who underwent surgical resections and radiotherapy twice in a previous hospital was referred to our hospital. Similar to that in case 1, proton beam therapy after debulking surgery and omental wrapping was performed. She died of lymph node metastasis after 31 months. Case 3: A 75-year-old man was diagnosed with unresectable local recurrence of rectal cancer. He underwent combination therapy and is doing well without any recurrence for 43 months. Case 4: A 57-yearold woman was also diagnosed with unresectable local recurrence. She underwent the same combination therapy after systemic chemotherapy. She died of lymph node metastasis after 11 months.

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

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.

Evaluation of Diaphragm Position Variations During Proton Therapy for Pediatric Patients With Neuroblastoma.

Background To evaluate the respiratory-induced intrafractional diaphragm motion and interfractional diaphragm displacement in pediatric patients with neuroblastoma (NBL). Materials and methods Ten pediatric patients with a mean age of 4.5 years (range: 1.8-8.7 years) with abdominal NBL treated with proton therapy (PT) have been evaluated. Intrafractional motion and interfractional displacement have been analyzed by using cine radiography and orthogonal X-ray images, respectively. In each case, the cranio-caudal positions of the diaphragm have been measured as an index. This study has investigated the possible correlations between intrafractional diaphragm motion and height. Additionally, interfractional displacement and its time trend during the treatment course have been analyzed. Results The average right and left diaphragm intrafractional motions of 8.3 mm (range: 4.4-11.5 mm) and 6.4 mm (range: 2.2-11.8 mm) were observed, respectively; however, no significant correlation has been observed with height. An interfractional displacement of 5 mm or more has been observed in 20 out of 152 fractions (13%). The average absolute value of the interfractional displacement was 2.5 mm (range: 0-8.6 mm). Interfractional displacement did not show a peculiar tendency throughout the treatment period. Conclusions It was suggested that respiratory-induced diaphragm position variation in children varies greatly among individuals, and accurately estimating it based on height is difficult. Thus, these individual evaluations are considered indispensable.

The Japanese nationwide cohort data of proton beam therapy for liver oligometastasis in breast cancer patients.

A nationwide multicenter cohort study on particle therapy was launched by the Japanese Society for Radiation Oncology in Japan in May 2016. We analyzed the outcome of proton beam therapy (PBT) for liver oligometastasis in breast cancers. Cases in which PBT was performed at all Japanese proton therapy facilities between May 2016 and February 2019 were enrolled. The patients were selected based on the following criteria: the primary cancer was controlled, liver recurrence without extrahepatic tumors and no more than three liver lesions. Fourteen females, with a median age of 57 years (range, 44-73) and 22 lesions, were included. The median lesion size, fraction (fr) size and biological effective dose were 44 (20-130) mm, 6.6 (2-8) gray (Gy) (relative biological effectiveness)/fr and 109.6 (52.7-115.2) Gy, respectively. The median follow-up period was 22.8 (4-54) months. The 1-, 2- and 3-year local control (LC) rates of liver metastasis from breast cancer were 100% for all. The 1-, 2- and 3-year overall survival rates were 85.7, 62.5 and 62.5%, respectively. The 1-, 2- and 3-year progression-free survival (PFS) rates were 50.0%, 33.3%, and 16.7%, respectively. The median PFS time was 16 months. Only one patient did not complete PBT due to current disease progression. One patient had Grade 3 radiation-induced dermatitis. None of the patients experienced radiation-induced liver failure during the acute or late phase. Owing to the low incidence of adverse events and the high LC rate, PBT appears to be a feasible option for liver oligometastasis in breast cancers.

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.

Radiological Cutoff Values for Diagnosis of Lymph Node Metastasis in Colorectal Cancer With Multilevel Analysis.

Background/Aim: A cutoff value for lymph node diameter in colorectal cancer lymph node metastases has not been established. This prospective study aimed to investigate the direct association between swollen lymph nodes identified on preoperative computed tomography (CT) and pathological findings and proposed a cutoff value. Patients and Methods: We enrolled patients scheduled to undergo curative surgery with lymph node dissection for colorectal adenocarcinoma who underwent preoperative contrast-enhanced CT and had swollen lymph nodes ≥7 mm in diameter. Two gastrointestinal surgeons intraoperatively identified the target lymph nodes to assess the association between lymph node diameter and pathological findings. The diagnostic performance for lymph node metastasis was determined using multi-level logistic modelling. Results: A total of 109 patients were enrolled, and 225 swollen lymph nodes were pathologically evaluated. Using a cutoff value of ≥9 mm for the short diameter, the positive and negative predictive values, sensitivity, and specificity were 100.0% (99.6%-100.0%), 99.9% (99.1%-100.0%), 62.0% (45.6%-76.0%), and 84.9% (67.0%-94.0%), respectively. Conclusion: The cutoff value for improving the positive predictive value for the preoperative lymph node metastasis diagnosis in colorectal cancer patients should be at least 9 mm in diameter.

Optimal Bladder Volume for Hypofractionated Proton Therapy in Each Localized Prostate Cancer Risk Group.

Background This study aimed to determine the optimal bladder volume (BV) for hypofractionated proton therapy in prostate cancer (PC). Materials and methods Two hundred patients with PC were enrolled in this study and classified into low-, intermediate-, and high-risk groups. Treatment planning was performed by assuming a hypofractionated schedule of 63 Gy (relative biological effectiveness) in 21 fractions. The dose indices of the bladder (V60 and V50) were calculated and classified into four groups according to the BV. A cutoff value with a 95% confidence interval was calculated on the basis of the mean and standard deviation of the dose indices. These values were compared with the dose constraints (V60 < 15 % and V50 < 30 %). Results The dose indices were higher in the high-risk group than in the other risk groups. The cutoff value exceeded dose constraints in the low- and intermediate-risk groups with a BV of â‰¦ 149 cc. Additionally, the cutoff value exceeded the dose constraint in the high-risk group with a BV of ≦ 199 cc. In all the cases, the group with a BV of â‰§ 200 cc was below the dose constraint. Conclusions In this study, the relationship between the dose and volume of the bladder in hypofractionated PT for PC was evaluated using a 95% CI to determine the optimal BV. The BV should be changed for each risk group, and a larger BV is required for a high-risk group than for other risk groups.

The Japanese nationwide cohort data of proton beam therapy for liver oligometastasis in esophagogastric cancer patients.

A nationwide multicenter cohort study on particle therapy was launched by the Japanese Society for Radiation Oncology in Japan in May 2016. We analyzed the outcome of proton beam therapy (PBT) for liver oligometastasis of esophagogastric cancers. Cases in which PBT was performed at all PBT facilities in Japan between May 2016 and February 2019 were enrolled. The patients were selected based on the following criteria: controlled primary cancer, liver recurrence without extrahepatic tumors and no more than three liver lesions. Twenty-two males and two females with a median age of 69 (range, 52-80) years and 35 lesions were included. This study included 6 patients with esophageal and 18 patients with gastric cancer. The median lesion size, fraction size and biological effective dose (BED)10 were 32 (7-104) mm, 3.8 gray (relative biological effect)/fractions (Gy (RBE)/fr) (2-8 Gy (RBE)/fr) and 96.9 (88.8-115.2) Gy, respectively. The median follow-up period was 18 (4-47) months. The 1-, 2- and 3-year overall survival (OS) rates were 75, 51.8 and 45.3%, respectively, and the median OS was 25.3 months. The 1-, 2- and 3-year cumulative local recurrence (LR) rates were 3, 6 and 6%, respectively. Patients' age (P < 0.01), performance status (P = 0.017) and tumor size (P = 0.024) were significant OS-related factors. No Grade 3 or higher adverse events (AEs) were observed. Owing to the low incidence of AEs and the low LR cumulative incidence, PBT is a feasible option for liver oligometastasis of esophagogastric cancers.

Outcomes and Prognostic Factors for Locally Recurrent Rectal Cancer Treated With Proton Beam Therapy.

Purpose: Our objective was to report the outcome and prognostic factors for patients with locally recurrent rectal cancer (LRRC) treated with proton beam therapy (PBT) at our institution. Methods and Materials: The study included PBT-treated patients with LRRC between December 2008 and December 2019. Treatment response was stratified using an initial imaging test after PBT. Overall survival (OS), progression-free survival (PFS), and local control (LC) were estimated using the Kaplan-Meier method. Each outcome's prognostic factors were verified using the Cox proportional hazards model. Results: Twenty-three patients were enrolled (median follow-up, 37.4 months). There were 11 patients with complete response (CR) or complete metabolic response (CMR), 8 with partial response or partial metabolic response, 2 with stable disease or stable metabolic response, and 2 with progressive disease or progressive metabolic disease. Three- and 5-year OS, PFS, and LC were 72.1% and 44.6%, 37.9% and 37.9%, and 55.0% and 47.2%, respectively, with 54.4 months' median survival time. The maximum standardized uptake value of fluorine-18-fluorodeoxyglucose-positron emission tomography-computed tomography (18F-FDG-PET/CT) before PBT (cutoff value, 10) showed significant differences in OS (P = .03), PFS (P = .027), and LC (P = .012). The patients who achieved CR or CMR after PBT had significantly better LC than those with non-CR or non-CMR (hazard ratio, 4.49; 95% confidence interval, 1.14-17.63; P = .021). Older patients (aged ≥65 years) had significantly higher LC and PFS rates. Patients with pain before PBT and larger tumors (≥30 mm) also had significantly lower PFS. Of 23 patients, 12 (52%) experienced further local recurrence after PBT. One patient developed grade 2 acute radiation dermatitis. Regarding late toxicity, grade 4 late gastrointestinal toxic effects were recorded in 3 patients, in 2 of whom reirradiation was associated with further local recurrence after PBT. Conclusions: The results showed that PBT may have potential to be a good treatment option for LRRC. 18F-FDG-PET/CT before and after PBT may be useful for assessing tumor response and predicting outcomes.

Effectiveness of proton beam therapy for liver oligometastatic recurrence in patients with postoperative esophagus cancer.

There are several reports of hepatic resection for postoperative hepatic metastatic recurrence of esophageal cancer. However, it is unclear whether surgery is the best local treatment for liver metastases. Thus, this study aimed to retrospectively analyze proton beam therapy (PBT) for postoperative liver metastatic recurrence of esophageal cancer without extrahepatic lesions and examine outcomes and adverse events. This single-center historical cohort study selected patients who underwent PBT at our proton therapy center between 2012 and 2018. The patients were selected based on the following criteria: primary esophagus carcinoma was resection and metachronous liver oligometastasis recurrence without extrahepatic tumors and no more than three liver metastases. This study included seven males with a median age of 66 (range, 58-78) years, and 15 lesions were included in the study. The median tumor size was 22.6 (7-55.3) mm. The most frequent dose was 72.6 Gy relative biological effect (RBE)/22 fractions (fr) for four lesions and 64 Gy (RBE)/8 fr for four lesions. The median survival time was 35.5 (13.2-119.4) months. The 1-, 2- and 3-year overall survival (OS) rates were 100%, 57.1% and 42.9%, respectively. The median progression-free survival (PFS) time was 8.7 (1.2-44.1) months. The 1-, 2- and 3-year PFS rates were 28.6%. The 1-, 2- and 3-year local control (LC) rates were 100%. No grade ≥4 radiation-induced adverse events (AEs) were observed. We conclude that PBT can be considered an alternative to hepatic resection for recurrent liver metastases postoperative esophageal cancer.

Proton Beam Therapy for Lung Oligometastatic Recurrence in Patients With Esophageal Cancer.

Local treatment of oligometastatic esophagogastric cancer has been reported to improve overall survival (OS) compared to systemic therapy alone. This study evaluated the feasibility and safety of proton beam therapy (PBT) for the treatment of lung oligometastatic recurrence in esophageal cancer patients. This single-center historical cohort study enrolled 11 patients who underwent PBT for lung oligometastasis from esophageal cancer between 2010 and 2019. The selection criteria were that the primary esophageal cancer was controlled and no more than three lung metastases without outside lung tumors were present. OS, progression-free survival (PFS), and local control (LC) rates and adverse events (AEs) were assessed. Factors that may be related to OS were also investigated. The median follow-up period was 27.8 months (8.8-141.3 months). The one-, two-, and three-year OS rates were 81.8%, 72.7%, and 51.9%, respectively (median OS time: 43.7 months); PFS rates were 45.5%, 27.3%, and 27.3%, respectively (median PFS time: 8.8 months); and LC rates were 92.3%, 72.7%, and 72.7%, respectively. The eighth edition of tumor-node-metastasis (TNM) classification for esophageal cancer was the only significant OS-related factor (p = 0.0309). No grade ≥ 3 AEs were observed. Based on the low incidence of AEs and acceptable LC rate, PBT is a feasible option for the treatment of lung oligometastasis in esophageal cancer patients.