[A Case of Intrahepatic Cholangiocarcinoma in Contact with the Gastroduodenal Anastomosis in Which Proton Beam Therapy Was Performed after Placement of an Absorbable Spacer].

Chemotherapy is the standard therapy for unresectable intrahepatic cholangiocarcinoma(ICC), but chemotherapy is not efficacious. Proton beam therapy(PBT)has been covered by Japanese health insurance for ICC since 2022, and the number of cases is expected to increase. In some cases, irradiation is difficult due to the close proximity of the gastrointestinal tract to the tumor. We report our management of a patient with ICC close to the gastrointestinal tract. The patient was a 69-year- old woman with a history of distal gastrectomy and Billroth-Ⅰ reconstruction for gastric cancer. A CT scan showed a tumor in liver S3; a biopsy revealed ICC. Because the tumor was in contact with the gastroduodenal anastomosis, we placed an absorbable spacer and performed PBT. After the treatment, the tumor shrank slightly. Although the liver is anatomically adjacent to the digestive tract, the placement of absorbable spacers facilitates performing PBT without adverse events, and is thus considered a useful treatment.

Feasibility of transrectal and transperineal fiducial marker placement for prostate cancer before proton therapy.

BACKGROUND: To compare the feasibility of transrectal and transperineal fiducial marker placement for prostate cancer before proton therapy. MATERIALS AND METHODS: From 2013 to 2015, the first 40 prostate cancer patients that were scheduled for proton therapy underwent transrectal fiducial marker placement, and the next 40 patients underwent transperineal fiducial marker placement (the first series). Technical and clinical success and pain scores were evaluated. In the second series (n = 280), the transrectal or transperineal approach was selected depending on the presence/absence of comorbidities, such as blood coagulation abnormalities. Seven patients refused to undergo the procedure. Thus, the total number of patients across both series was 353 (262 and 91 underwent the transrectal and transperineal approach, respectively). Technical and clinical success, complications, marker migration and the distance between the two markers were evaluated. RESULTS: In the first series, the technical and clinical success rates were 100% in both groups. The transrectal group exhibited lower pain scores than the transperineal group. The overall technical success rates of the transrectal and transperineal groups were 100% (262/262) and 99% (90/91), respectively (P > 0.05). The overall clinical success rate was 100% in both groups, and there were no major complications in either group. The migration rates of the two groups did not differ significantly. The mean distance between the two markers was 25.6 ± 7.1 mm (mean ± standard deviation) in the transrectal group and 31.9 ± 5.2 mm in the transperineal group (P < 0.05). CONCLUSION: Both the transrectal and transperineal fiducial marker placement methods are feasible and safe.

Long-term multidisciplinary treatment including proton therapy for a recurrent low-grade endometrial stromal sarcoma and pathologically prominent epithelial differentiation: an autopsy case report.

BACKGROUND: Long-term follow-up reports of low-grade endometrial stromal sarcoma (LGESS) including its clinical course and pathological data are rare. We previously reported the case of a Japanese woman diagnosed with LGESS, who was treated with multidisciplinary therapy. She had been suffering from uterine cervical tumor diagnosed as cervical polyps, or fibroid in statu nascendi, since 24 years old. The patient had survived for 25 years with the disease. This report presents her progress and pathological change since the previous report. CASE PRESENTATION: At age 45, the patient experienced a relapse of the remnant LGESS tumor between the right diaphragm and liver. Although chemotherapy was not effective, the tumor was eliminated by proton therapy. At age 46 years, the remnant tumors outside the irradiated field were resected. The disease was originally diagnosed as "neuroendocrine carcinoma (NEC)" using the surgical specimen. Therefore, cisplatin and irinotecan combination chemotherapy were administered to treat the remnant dissemination. After 4 cycles of chemotherapy, the liver metastases had enlarged and were resected surgically. Consequently, no remnant tumor was visible in the abdominal cavity at the end of the surgery. To determine the origin of NEC, we examined the previously resected specimens obtained from her ileum at age 40 years. A boundary between the LGESS and neuroendocrine tumor grade 2 (NET G2)-like lesion was found in the tumor, indicating that the origin of these tumors was LGESS. After less than 2 years of chemotherapy and undergoing surgery, a relapse of the tumor in the liver induced biliary duct obstruction with jaundice, which was treated with endoscopic retrograde biliary drainage. Although pazopanib prolonged her life for 10 months, she died from sepsis at age 49 years, which was caused by the infection that spread to the liver metastatic tumor via the stented biliary ducts. Autopsy revealed adenocarcinoma-like differentiation of the tumor. CONCLUSION: This LGESS patient has survived for a long time owing to multidisciplinary treatment including proton therapy. The LGESS tumor differentiated to NET G2-like tissue and then further to adenocarcinoma-like tissue during the long-term follow-up.

Dosimetric verification of IMPT using a commercial heterogeneous phantom.

The purpose of this study was to propose a verification method and results of intensity-modulated proton therapy (IMPT), using a commercially available heterogeneous phantom. We used a simple simulated head and neck and prostate phantom. An ionization chamber and radiochromic film were used for measurements of absolute dose and relative dose distribution. The measured doses were compared with calculated doses using a treatment planning system. We defined the uncertainty of the measurement point of the ionization chamber due to the effective point of the chamber and mechanical setup error as 2 mm and estimated the dose variation base on a 2 mm error. We prepared a HU-relative stopping power conversion table and fluence correction factor that were specific to the heterogeneous phantom. The fluence correction factor was determined as a function of depth and was obtained from the ratio of the doses in water and in the phantom at the same effective depths. In the simulated prostate plan, composite doses of measurements and calculations agreed within ±1.3% and the maximum local dose differences of each field were 10.0%. Composite doses in the simulated head and neck plan agreed within 4.0% and the maximum local dose difference for each field was 12.0%. The dose difference for each field came within 2% when taking the measurement uncertainty into consideration. In the composite plan, the maximum dose uncertainty was estimated as 4.0% in the simulated prostate plan and 5.8% in the simulated head and neck plan. Film measurements showed good agreement, with more than 92.5% of points passing a gamma value (3%/3 mm). From these results, the heterogeneous phantom should be useful for verification of IMPT by using a phantom-specific HU-relative stopping power conversion, fluence correction factor, and dose error estimation due to the effective point of the chamber.

A quality assurance for respiratory gated proton irradiation with range modulation wheel.

The purpose of this study was to provide periodic quality assurance (QA) methods for respiratory-gated proton beam with a range modulation wheel (RMW) and to clarify the characteristics and long-term stability of the respiratory-gated proton beam. A two-dimensional detector array and a solid water phantom were used to measure absolute dose, spread-out Bragg peak (SOBP) width and proton range for monthly QA. SOBP width and proton range were measured using an oblique incidence beam to the lateral side of a solid water phantom and compared between with and without a gating proton beam. To measure the delay time of beam-on/off for annual QA, we collected the beam-on/off signals and the dose monitor-detected pulse. We analyzed the results of monthly QA over a 15-month period and investigated the delay time by machine signal analysis. The dose deviations at proximal, SOBP center and distal points were -0.083 ± 0.25%, 0.026 ± 0.20%, and -0.083 ± 0.35%, respectively. The maximum dose deviation between with and without respiratory gating was -0.95% at the distal point and other deviations were within ±0.5%. Proximal and SOBP center doses showed the same trend over a 15-month period. Delay times of beam-on/off for 200 MeV/SOBP 16 cm were 140.5 ± 0.8 ms and 22.3 ± 13.0 ms, respectively. Delay times for 160 MeV/SOBP 10 cm were 167.5 ± 15.1 ms and 19.1 ± 9.8 ms. Our beam delivery system with the RMW showed sufficient stability for respiratory-gated proton therapy and the system did not show dependency on the energy and the respiratory wave form. The delay times of beam-on/off were within expectations. The proposed QA methods will be useful for managing the quality of respiratory-gated proton beams and other beam delivery systems.

Recovery from sublethal damage and potentially lethal damage : Proton beam irradiation vs. X­ray irradiation.

PURPOSE: In order to clarify the biological response of tumor cells to proton beam irradiation, sublethal damage recovery (SLDR) and potentially lethal damage recovery (PLDR) induced after proton beam irradiation at the center of a 10 cm spread-out Bragg peak (SOBP) were compared with those seen after X­ray irradiation. METHODS: Cell survival was determined by a colony assay using EMT6 and human salivary gland tumor (HSG) cells. First, two doses of 4 Gy/GyE (Gray equivalents, GyE) were given at an interfraction interval of 0-6 h. Second, five fractions of 1.6 Gy/GyE were administered at interfraction intervals of 0-5 min. Third, a delayed-plating assay involving cells in plateau-phase cultures was conducted. The cells were plated in plastic dishes immediately or 2-24 h after being irradiated with 8 Gy/GyE of X­rays or proton beams. Furthermore, we investigated the degree of protection from the effects of X­rays or proton beams afforded by the radical scavenger dimethyl sulfoxide to estimate the contribution of the indirect effect of radiation. RESULTS: In both the first and second experiments, SLDR was more suppressed after proton beam irradiation than after X­ray irradiation. In the third experiment, there was no difference in PLDR between the proton beam and X­ray irradiation conditions. The degree of protection tended to be higher after X­ray irradiation than after proton beam irradiation. CONCLUSION: Compared with that seen after X­ray irradiation, SLDR might take place to a lesser extent after proton beam irradiation at the center of a 10 cm SOBP, while the extent of PLDR does not differ significantly between these two conditions.

Acute toxicity of image-guided hypofractionated proton therapy for localized prostate cancer.

BACKGROUND: Hypofractionated proton therapy (HFPT) is expected to become an effective treatment approach for localized prostate cancer (PCa). The purpose of this study was to evaluate differences in acute toxicity among patients with localized PCa treated with either conventional fractionated proton therapy (CFPT) or HFPT. METHODS: A total of 526 eligible patients treated with proton therapy between February 2013 and May 2016 in three phase II trials were analyzed. We prescribed 74 gray relative biological effectiveness equivalents [Gy (RBE)]/37 fractions for low-risk patients and 78 Gy (RBE)/39 fractions for intermediate- and high-risk patients in the CFPT group (n = 254) and 60 Gy (RBE)/20 fractions for low-risk and 63 Gy (RBE)/21 fractions for intermediate- and high-risk patients in the HFPT group (n = 272). Patients were evaluated for acute toxicity with the Common Terminology Criteria for Adverse Events, version 4.0, and urinary quality-of-life change using the International Prostate Symptom Score (IPSS). RESULTS: No grade ≥3 acute toxicity was observed in either group. Among acute genitourinary toxicities, grade 2 rates were 15% (n = 38) in CFPT and 5.9% (n = 16) in HFPT (P ≤ 0.001). The median baseline IPSSs of the CFPT and HFPT groups were 7 (0-29) and 6 (0-31), respectively (P = 0.70). One-month post-treatment scores were 9 (0-32) and 11 (0-32), respectively (P = 0.036), and 6-month post-treatment scores were 7 (0-30) and 7 (0-33), respectively (P = 0.88). There were no significant differences in acute gastrointestinal toxicity between the two groups. CONCLUSION: Our results demonstrated the safety of HFPT for localized PCa patients in terms of acute toxicity.

Spot scanning proton therapy for unresectable bulky retroperitoneal dedifferentiated liposarcoma: a case report.

The development of effective treatment strategies for unresectable retroperitoneal sarcoma is desirable. Herein, we suggest that definitive proton therapy (PT) could be a promising treatment option, regardless of the large size of the tumor. A 52-year-old man presented with a discomfort of the lower abdomen. Computed tomography revealed a retroperitoneal tumor, measuring over 20 cm in the largest dimensions, which was surrounded by the gastrointestinal (GI) tract. Biopsy revealed dedifferentiated liposarcoma. Neoadjuvant chemotherapy was ineffective, and the tumor was ultimately deemed unresectable. The patient opted to receive PT instead of continuation of chemotherapy. Spot scanning PT (SSPT) at a total dose of 60.8 Gy (relative biological effectiveness) in 16 fractions was employed. SSPT administered a dose to the tumor while successfully sparing the surrounding GI tract. He did not receive any maintenance systemic therapy after PT. The tumor gradually shrunk over more than 7 years, with no evidence of recurrence outside the irradiation field. The initial measurable tumor volume of 2925 cc decreased to 214 cc at the final follow-up, seven and a half years after PT. The patient is alive without any severe complications.

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.

Dose Prescription to Isodose Lines in Static Multi-Beam Stereotactic Body Radiotherapy for Lung Tumors: Which Line Is Optimal?

This study investigated the appropriate dose prescription method in static multi-beam stereotactic body radiotherapy for lung tumors. Static multi-beam stereotactic body radiotherapy is a mainstream treatment in Japan. Based on the hypothesis that dose prescription to lower isodose lines may improve planning target volume dose coverage and decrease doses to organs at risk, we investigated changes in dose-volume histograms with prescription to various isodose lines for planning target volume in static multi-beam stereotactic body radiotherapy. In all treatment plans, 45 Gy in 4 fractions were prescribed to 95% of the planning target volume. By adjusting the leaf margins of each beam, various prescription isodose lines encompassing 95% volume of the planning target volume were generated. The prescription isodose lines investigated were 40, 50, 60, 70, 80 and 90% lines relative to the maximum dose of each planning target volume. The conformity index, homogeneity index, mean lung dose, and V5-V40 of the lung were evaluated. The dose was calculated by the adaptive convolve algorithm. The conformity index was lowest in the 70% or 80% isodose plan. The mean lung doses and V10-V40 of the lung decreased steeply from the 90% to the 70% isodose plan, and was lowest in the 60% and 70% isodose plans. These indices increased in the 40% and 50% isodose plans. The optimal stereotactic body radiotherapy plans appeared to be dose prescription to the 60% or 70% isodose line. Further investigation is warranted to clarify the advantage of using this method clinically.

Long-term survival outcomes and quality of life of image-guided proton therapy for operable stage I non-small cell lung cancer: A phase 2 study.

BACKGROUND AND PURPOSE: This study evaluated long-term efficacy, safety, and changes in quality of life (QOL) of patients after image-guided proton therapy (IGPT) for operable stage I non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: This single-institutional prospective phase 2 study enrolled patients with operable histologically confirmed stage IA or IB NSCLC (7th edition of UICC). The prescribed dose was 66 Gy relative biological effectiveness equivalents (GyRBE) in 10 fractions for peripheral lesions, or 72.6 GyRBE in 22 fractions for central lesions. The primary endpoint was the 3-year overall survival (OS). The secondary endpoints included disease control, toxicity, and changes in QOL score. RESULTS: We enrolled 43 patients (median age: 68 years; range, 47-79 years) between July 2013 to January 2021, of whom 41 (95 %) had peripheral lesions and 27 (63 %) were stage IA. OS, local control, and progression-free survival rates were 95 % (95 % CI: 83-99), 95 % (82-99), and 86 % (72-94), respectively, at 3 years, and 83 % (66-92), 95 % (82-99), and 77 % (60-88), respectively, at 7 years. Four patients (9 %) developed grade 2, and one patient (2 %) developed grade 3 radiation pneumonitis. No other grade 3 or higher adverse events were observed. In the QOL analysis, global QOL remained favorable; however, approximately 40 % of patients reported dyspnea at 3 and 24 months. CONCLUSION: Our findings suggest that IGPT provides effective disease control and survival in operable stage I NSCLC, particularly for peripheral lesions. Moreover, toxicity associated with IGPT was minimal, and patients reported favorable QOL.

Proton Beam Therapy for Hepatocellular Carcinoma: Multicenter Prospective Registry Study in Japan.

PURPOSE: A prospective multicenter registry study was started May 2016 in Japan to evaluate the efficacy and safety of proton beam therapy (PBT) for hepatocellular carcinoma (HCC). METHODS AND MATERIALS: Patients who received PBT for HCC from May 2016 to June 2018 were registered in the database of the Particle Beam Therapy Committee and Subcommittee of the Japanese Society for Radiation Oncology. Overall survival (OS), progression-free survival (PFS), and local recurrence were evaluated. RESULTS: Of the 755 registered patients, 576 with initial PBT and no duplicate cancer were evaluated. At final follow-up, 322 patients were alive and 254 had died. The median follow-up period for survivors was 39 months (0-58 months). The median OS time of the 576 patients was 48.8 months (95% CI, 42.0-55.6 months) and the 1-, 2-, 3-, and 4-year OS rates were 83.8% (95% CI, 80.5%-86.6%), 68.5% (64.5%-72.2%), 58.2% (53.9%-62.2%), and 50.1% (44.9%-55.0%), respectively. Recurrence was observed in 332 patients, including local recurrence in 45 patients. The median PFS time was 14.7 months (95% CI, 12.4-17.0 months) and the 1-, 2-, 3-, and 4-year PFS rates were 55.2% (95% CI, 51.0%-59.2%), 37.5% (33.5%-41.5%), 30.2% (26.3%-34.2%), and 22.8% (18.5%-27.4%), respectively. The 1-, 2-, 3-, and 4-year OS rates were significantly higher for tumor size <5 versus 5 to 10 cm (P < .001) and <5 versus ≥10 cm (P < .001); Child-Pugh score A/B versus C (P < .001); and distance of the tumor from the gastrointestinal tract <1 versus 1 to 2 cm (P < .008) and <1 versus >2 cm (P < .001). At final follow-up, 27 patients (4.7%) had late adverse events of grade 3 or higher, with liver failure (n = 7), and dermatitis (n = 7) being most common. CONCLUSIONS: This multicenter prospective data registry indicated that PBT for HCC gives good therapeutic effects (3-year local control rate of 90%) with a low risk of severe late adverse events.

Change in preference for vegetables and their perceptual attributes as a function of age and pickiness.

Preference for vegetables is influenced by various factors, including demographic, psychological, socio-environmental, and genetic factors. This study confirmed that age, pickiness, and perceptual attributes were predictors of preference for vegetables and examined how preference for vegetables and their perceptual attributes varies with age and pickiness. Children (8-14 years, n = 420), youth (15-34 years, n = 569), middle-aged adults (35-64 years, n = 726), and older adults (65-85 years, n = 270) were asked which vegetables they liked (or disliked) and which perceptual attributes of each vegetable they liked (or disliked). On the basis of their responses, an overall preference score and a preference sub-score for each perceptual attribute were calculated. Participants in each age group were classified into four statuses (non-, mild, moderate, and severe) according to their pickiness scores. Multiple regression analysis revealed that age and preference sub-scores for eight perceptual attributes (sweetness, sourness, bitterness, umami, pungency, orthonasal aroma, texture, and appearance) were positive predictors of overall preference score and that pickiness score and four perceptual attributes (saltiness, astringency, retronasal aroma, and aftertaste) were negative predictors. In addition, overall preference score and preference sub-scores for perceptual attributes other than saltiness increased with increasing age group and decreasing picker status; however, preference sub-scores for at least one of the six perceptual attributes (bitterness, astringency, pungency, orthonasal aroma, retronasal aroma, and aftertaste) exhibited negative values in children, youth, and pickers (mild, moderate, and severe). The increase in preference for these perceptual attributes might be an indicator of the adultization of food perception and the expansion of food acceptance.

Dosimetric impact of systematic spot position errors in spot scanning proton therapy of head and neck tumor.

Purpose: The spot position is an important beam parameter in the quality assurance of scanning proton therapy. In this study, we investigated dosimetric impact of systematic 15 spot position errors (SSPE) in spot scanning proton therapy using three types of optimization methods of head and neck tumor. Materials and Methods: The planning simulation was performed with ± 2 mm model SSPE in the X and Y directions. Treatment plans were created using intensity-modulated proton therapy (IMPT) and single-field uniform dose (SFUD). IMPT plans were created by two optimization methods: with worst-case optimization (WCO-IMPT) and without (IMPT). For clinical target volume (CTV), D95%, D50%, and D2cc were used for analysis. For organs at risk (OAR), Dmean was used to analyze the brain, cochlea, and parotid, and Dmax was used to analyze brainsetem, chiasm, optic nerve, and cord. Results: For CTV, the variation (1 standard deviation) of D95% was ± 0.88%, 0.97% and 0.97% to WCO-IMPT, IMPT, and SFUD plan. The variation of D50% and D2cc of CTV showed <0.5% variation in all plans. The dose variation due to SSPE was larger in OAR, and worst-case optimization reduced the dose variation, especially in Dmax. The analysis results showed that SSPE has little impact on SFUD. Conclusions: We clarified the impact of SSPE on dose distribution for three optimization methods. SFUD was shown to be a robust treatment plan for OARs, and the WCO can be used to increase robustness to SSPE in IMPT.

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.

Lobectomy versus proton therapy for stage I non-small cell lung cancer.

OBJECTIVE: Lobectomy is the standard treatment for patients with early-stage non-small cell lung cancer (NSCLC). In recent years, an increasing number of patients with lung cancer have been treated using proton therapy (PT). We conducted a propensity score-matched analysis to compare the treatment outcomes of these 2 modalities. METHODS: We retrospectively reviewed data from 275 patients with histologically confirmed clinical stage I NSCLC who underwent lobectomy (n = 206) or PT (n = 69) at our institution from July 2013 to December 2020. The end points were overall survival (OS), cause-specific survival, recurrence-free survival (RFS), local control, regional lymph node control, and distant control. Propensity score matching was performed to reduce selection bias in the 2 groups. RESULTS: The matched cohort consisted of 59 patients who underwent lobectomy and 59 patients who underwent PT with a median follow-up period of 50 months. There were no significant differences in OS (P = .26), cause-specific survival (P = .33), RFS (P = .53), local control (P = .41), regional lymph node control (P = .98), and distant control (P = .31). In the lobectomy and PT groups, the 5-year OS rate was 85.8% and 79.1%, respectively, the RFS rate was 82.3% and 77.8%, and the local control rate was 92.1% and 96.6%. CONCLUSIONS: We found no difference in survival or disease control between lobectomy and PT in patients with histologically confirmed clinical stage I NSCLC. Despite these findings, the potential for unmeasured confounding factors remains, and randomized control trials are needed to better compare these treatment modalities.

Factors related to fixedness after transbronchial fiducial marker placement for image-guided proton therapy: A retrospective study.

BACKGROUND: The usefulness of transbronchially inserted gold fiducial markers has been reported in radiation therapy and proton therapy for mobile lesions, such as lung tumors. However, there is occasional dropout of inserted markers. This retrospective study investigated the factors related to dropout of markers inserted for image-guided proton therapy (IGPT). METHODS: Between June 2013 and October 2021, 535 markers were inserted in 171 patients with lung tumors. We investigated whether marker dropout was affected by the location of marker insertion, distance between the marker and the chest wall (DMC), and difference in forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC). Marker dropout from the time of planning computed tomography (CT) to follow-up CT was also evaluated. RESULTS: Of the 535 inserted markers, 417 were confirmed on planning CT and 356 on follow-up CT after IGPT. Multivariate analysis revealed that marker insertion into the upper lobe and FEV1/FVC ≥70% were factors associated with total marker dropout. Marker dropout between planning CT and follow-up CT was associated with DMC, FEV1/FVC ≥70%, and planning CT performed within 4 days of marker insertion. CONCLUSIONS: Marker dropout can be minimized by inserting markers more peripherally, by considering the planned insertion location, and FEV1/FVC. Additionally, planning CT should be scheduled at least 5 days after marker insertion.

Severe skin ulcer caused by taking lenvatinib after proton beam therapy.

A 69-year-old man was treated with lenvatinib after three sessions of proton beam therapy (PBT) for hepatocellular carcinoma. Five months after administration of lenvatinib, a dermatitis with huge skin ulcer formed in the site of PBT irradiation. Lenvatinib was immediately withdrawn, but the skin ulcer continued growing until about 2 weeks later. With topical and antibiotic treatment, the skin ulcer resolved after about 4 months. After administration of lenvatinib, potential skin damage due to PBT at the irradiated site may have become apparent. This is the first report describing skin ulcer by the combination of lenvatinib administration and PBT.

Proton beam therapy for extrahepatic biliary tract cancer: Analysis with prospective multi-institutional patients' registration database, Proton-Net.

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 <) were identified as poor prognostic factors for OS. PBT-related grade 3 ≤ acute and late adverse events occurred in 5.4% and 4.3% of patients, respectively, including one gastrointestinal late toxicity (duodenal ulcer). Conclusions: This is the largest prospectively accumulated series of PBT for EBC, and PBT showed favorable outcomes with acceptable toxicity profiles.