A retrospective evaluation of therapeutic efficacy and safety of chemoradiotherapy in older patients (aged ≥ 75 years) with limited-disease small cell lung cancer: insights from two institutions and review of the literature.

BACKGROUND: The standard treatment for patients in good general condition with limited-disease small cell lung cancer (LD-SCLC) is concurrent platinum/etoposide chemotherapy and thoracic radiotherapy (TRT). However, the efficacy and safety of chemoradiotherapy (CRT) in older patients with LD-SCLC has not been fully explored; moreover, the optimal treatment for this patient group remains unclear. This study aimed to investigate the feasibility and efficacy of CRT in older patients with LD-SCLC. PATIENTS AND METHODS: From April 2007 to June 2021, consecutive older patients (aged ≥ 75 years) with stage I to III SCLC who received concurrent or sequential CRT at two institutions were retrospectively evaluated for efficacy and toxicity of CRT. RESULTS: A total of 32 older patients underwent concurrent (n = 19) or sequential (n = 13) CRT for LD-SCLC. The median ages of the patients in the concurrent and sequential CRT groups were 77 (range: 75-81) years and 79 (range: 76-92) years, respectively. The median number of chemotherapeutic treatment cycles was four (range, 1-5), and the response rate was 96.9% in all patients (94.7% in concurrent and 100% in sequential CRT groups). The median progression-free survival (PFS) and median overall survival (OS) for all patients were 11.9 and 21.1 months, respectively. The median PFS was 13.0 and 9.0 months in the concurrent CRT and sequential CRT groups, respectively, with no statistically significant difference (p = 0.67). The median OS from the initiation of CRT was 19.2 and 23.5 months in the concurrent and sequential CRT groups, respectively (p = 0.46). The frequencies of Grade ≥ 3 hematological adverse events were as follows: decreased white blood cell count, 20/32 (62.5%); decreased neutrophil count, 23/32 (71.9%); anemia, 6/32 (18.8%); decreased platelet count, 7/32 (21.9%); and febrile neutropenia, 3/32 (9.4%). Treatment-related deaths occurred in one patient from each group. CONCLUSIONS: Although hematological toxicities, particularly reduced neutrophil count, were severe, CRT showed favorable efficacy in both concurrent and sequential CRT groups. However, concurrent CRT may not be feasible for all older patients with LD-SCLC; accordingly, sequential CRT may be considered as a treatment of choice for these patients. Further prospective trials are warranted to identify optimal treatment strategies for this patient group.

The Glasgow Prognostic Score as a Predictor of Survival after Chemoradiotherapy for Limited-Disease Small Cell Lung Cancer.

INTRODUCTION: Established biomarkers for predicting chemoradiotherapy efficacy for limited-disease small cell lung cancer (LD-SCLC) are lacking. The inflammation-based Glasgow Prognostic Score (GPS), comprising serum C-reactive protein (CRP) and albumin levels, can predict survival in advanced cancer. This study investigated whether metabolic and inflammatory markers, including the GPS, can predict the efficacy of chemoradiotherapy in patients with LD-SCLC. METHODS: We retrospectively analyzed 124 patients who underwent chemoradiotherapy for LD-SCLC at two institutions between April 2007 and June 2021, and assessed the prognostic significance of various metabolic and inflammatory markers. The GPS was calculated using the CRP and albumin concentrations, and categorized as follows: 0, CRP <1.0 mg/dL and albumin ≥3.5 mg/dL; 1, elevated CRP or decreased albumin; and 2, CRP ≥1.0 mg/dL and albumin<3.5 mg/dL. Differences in progression-free survival (PFS) and overall survival (OS) were examined using Kaplan-Meier curves and Cox proportional-hazard models. RESULTS: The overall response rate was 95.1% (95% confidence interval [CI]: 89.6-97.9%). The median PFS and OS from chemoradiotherapy initiation were 12.6 (95% CI: 9.9-15.4) and 29.0 (95% CI: 24.8-45.5) months, respectively. The GPS demonstrated independent predictive ability for the effectiveness of chemoradiotherapy, wherein favorable scores (GPS 0-1) were significantly correlated with superior PFS and OS compared to unfavorable scores (GPS 2: PFS: 14.8 vs. 6.7 months, p = 0.0001; OS: 35.4 vs. 11.0 months, p < 0.0001). CONCLUSION: This preliminary examination revealed that the GPS was significantly associated with PFS and OS in patients undergoing chemoradiotherapy for LD-SCLC, indicating its potential utility in assessing the therapeutic outcomes in LD-SCLC.

Cost-Effectiveness Comparison of Carbon-Ion Radiation Therapy and Transarterial Chemoembolization for Hepatocellular Carcinoma.

Purpose: Carbon-ion radiation therapy (CIRT) is a treatment option for patients with hepatocellular carcinoma (HCC) that results in better outcomes with fewer side effects despite its high cost. This study aimed to evaluate the cost-effectiveness of CIRT for HCC from medical and economic perspectives by comparing CIRT and transarterial chemoembolization (TACE) in patients with localized HCC who were ineligible for surgery or radiofrequency ablation. Methods and Materials: This study included 34 patients with HCC who underwent either CIRT or TACE at Gunma University between 2007 and 2016. Patient characteristics were employed to select each treatment group using the propensity score matching method. Life years were used as the outcome indicator. The CIRT technical fee was ¥3,140,000; however, a second CIRT treatment on the same organ within 2 years was performed for free. Results: Our study showed that CIRT was dominant over TACE, as the CIRT group had a higher life year (point estimate, 2.75 vs 2.41) and lower total cost (mean, ¥4,974,278 vs ¥5,284,524). We conducted a sensitivity analysis to validate the results because of the higher variance in medical costs in the TACE group, which demonstrated that CIRT maintained its cost effectiveness with a high acceptability rate. Conclusions: CIRT is a cost-effective treatment option for localized HCC cases unsuitable for surgical resection.

Carbon-ion radiotherapy for oligometastatic liver disease: A national multicentric study by the Japan Carbon-Ion Radiation Oncology Study Group (J-CROS).

Reports on the therapeutic efficacy and safety of carbon-ion radiotherapy (C-ion RT) for oligometastatic liver disease are limited, with insufficient evidence. This study aimed to evaluate the clinical outcomes of C-ion RT for oligometastatic liver disease at all Japanese facilities using the nationwide cohort data. We reviewed the medical records to obtain the nationwide cohort registry data on C-ion RT between May 2016 and June 2020. Patients (1) with oligometastatic liver disease as confirmed by histological or diagnostic imaging, (2) with ≤3 synchronous liver metastases at the time of treatment, (3) without active extrahepatic disease, and (4) who received C-ion RT for all metastatic regions with curative intent were included in this study. C-ion RT was performed with 58.0-76.0 Gy (relative biological effectiveness [RBE]) in 1-20 fractions. In total, 102 patients (121 tumors) were enrolled in this study. The median follow-up duration for all patients was 19.0 months. The median tumor size was 27 mm. The 1-year/2-year overall survival, local control, and progression-free survival rates were 85.1%/72.8%, 90.5%/78.0%, and 48.3%/27.1%, respectively. No patient developed grade 3 or higher acute or late toxicity. C-ion RT is a safe and effective treatment for oligometastatic liver disease and may be beneficial as a local treatment option in multidisciplinary treatment.

Carbon-Ion Radiotherapy Combined with Concurrent Chemotherapy for Locally Advanced Pancreatic Cancer: A Retrospective Case Series Analysis.

Systemic chemotherapy has significantly improved in recent years. In this study. the clinical impact of carbon-ion radiotherapy (CIRT) with concurrent chemotherapy for locally advanced unresectable pancreatic cancer (URPC) was evaluated. METHODS: Patients with URPC who were treated with CIRT between January 2016 and December 2020 were prospectively registered and analyzed. The major criteria for registration were (1) diagnosed as URPC on imaging; (2) pathologically diagnosed adenocarcinoma; (3) no distant metastasis; (4) Eastern Cooperative Oncology Group performance status of 0-2; (5) tumors without gastrointestinal tract invasion; and (6) available for concurrent chemotherapy. Patients who received neoadjuvant chemotherapy (NAC) for more than one year prior to CIRT were excluded. RESULTS: Forty-four patients met the inclusion criteria, and thirty-seven received NAC before CIRT. The median follow-up period of living patients was 26.0 (6.0-68.6) months after CIRT. The estimated two-year overall survival, local control, and progression-free survival rates after CIRT were 56.6%, 76.1%, and 29.0%, respectively. The median survival time of all patients was 29.6 months after CIRT and 34.5 months after the initial NAC. CONCLUSION: CIRT showed survival benefits for URPC even in the multiagent chemotherapy era.

Robust Beam Selection Based on Water Equivalent Thickness Analysis in Passive Scattering Carbon-Ion Radiotherapy for Pancreatic Cancer.

Carbon-ion radiotherapy (CIRT) is one of the most effective radiotherapeutic modalities. This study aimed to select robust-beam configurations (BC) by water equivalent thickness (WET) analysis in passive CIRT for pancreatic cancer. The study analyzed 110 computed tomography (CT) images and 600 dose distributions of eight patients with pancreatic cancer. The robustness in the beam range was evaluated using both planning and daily CT images, and two robust BCs for the rotating gantry and fixed port were selected. The planned, daily, and accumulated doses were calculated and compared after bone matching (BM) and tumor matching (TM). The dose-volume parameters for the target and organs at risk (OARs) were evaluated. Posterior oblique beams (120-240°) in the supine position and anteroposterior beams (0° and 180°) in the prone position were the most robust to WET changes. The mean CTV V95% reductions with TM were -3.8% and -5.2% with the BC for gantry and the BC for fixed ports, respectively. Despite ensuring robustness, the dose to the OARs increased slightly with WET-based BCs but remained below the dose constraint. The robustness of dose distribution can be improved by BCs that are robust to ΔWET. Robust BC with TM improves the accuracy of passive CIRT for pancreatic cancer.

Comprehensive analysis of Japanese nationwide cohort data of particle beam therapy for pulmonary, liver and lymph node oligometastases: particle beam therapy versus high-precision X-ray radiotherapy.

Japanese national oncological experts convened to evaluate the efficacy and safety of particle beam therapy (PT) for pulmonary, liver and lymph node oligometastases (P-OM, L-OM and LN-OM, respectively) and to conduct a statistically comparative analysis of the local control (LC) rate and overall survival (OS) rate of PT versus those of X-ray stereotactic body radiotherapy (X-SBRT) and X-ray intensity-modulated radiotherapy (X-IMRT). They conducted [1] an analysis of the efficacy and safety of metastasis-directed therapy with PT for P-OM, L-OM and LN-OM using a Japanese nationwide multi-institutional cohort study data set; [2] a systematic review of X-ray high-precision radiotherapy (i.e. X-SBRT/X-IMRT) and PT for P-OM, L-OM and LN-OM; and [3] a statistical comparison between LC and OS of the cohort data set in PT and that of the extracted historical data set in X-SBRT/X-IMRT from the preceding systematic review. Safety was evaluated as the incidence of grade ≥ 3 adverse events, while statistical comparisons of LC and OS were conducted by estimating the incidence rate ratios (IRR) for local progression and mortality, respectively. This study demonstrated that PT provided durable LC (3-year LC rate: 72.8-83.2%) with acceptable OS (3-year OS rate: 38.5-68.1%) and risk of severe toxicity incidence of 0.8-3.5% in radical metastasis-directed therapy for P-OM, L-OM and LN-OM. Compared to LC with X-SBRT or X-IMRT, LC with PT was potentially superior for P-OM; superior for L-OM; and equivalent for LN-OM. In particular, this study demonstrated that PT may be a new treatment option for L-OM tumors measuring > 5 cm.

Repeated Carbon-Ion Radiation Therapy for Intrahepatic Recurrent Hepatocellular Carcinoma.

PURPOSE: This retrospective study aimed to evaluate the safety and efficacy of repeated carbon-ion radiation therapy (CIRT) in patients with intrahepatic recurrent hepatocellular carcinoma (HCC). METHODS AND MATERIALS: We reviewed patients who underwent repeated CIRT for intrahepatic recurrent HCC between 2010 and 2020. RESULTS: Forty-one patients received multiple CIRT courses for HCC. During the second course, 17 (41.5%) and 24 (58.5%) of 41 patients underwent CIRT for local recurrence (LR) and intrahepatic recurrence after the first irradiation, respectively. The median age at the first course was 76 years, and the median tumor size in all the courses was 25 mm. Throughout all CIRT courses, the prescribed dose was 52.8 to 60.0 Gy (relative biological effectiveness), which was delivered in 4 to 12 fractions. The median follow-up period after the first and second CIRT was 40 and 21 months. Median overall survival (OS) after the first and second CIRT were 80 and 27 months, respectively. The 2- and 5-year OS after the first CIRT were 87.8% and 50.1%, and the 2-year OS rate after the second CIRT was 56.0%. The 1- and 2-year local control (LC) after the second CIRT was 93.4% and 83.0%, respectively. The median progression-free survival (PFS) after the second CIRT was 11 months. There were no significant differences in the LC and PFS between patients with LR and out-of-field recurrence (P = .83; 0.28, respectively). The albumin-bilirubin scores at 3 and 6 months after the second CIRT were not significantly different from those before irradiation. According to the Common Terminology Criteria for Adverse Events version 4.0, grade 4 or greater toxicities were not observed. CONCLUSIONS: Repeated CIRT for intrahepatic recurrent HCC was safe and effective, including reirradiation for LR. OS, LC, and PFS were satisfactory, and liver function was preserved. Repeated CIRT could be considered a treatment option for intrahepatic recurrent HCC.

Safety and Efficacy of Re-irradiation With Carbon-ion Radiotherapy for Pelvic Recurrence of Rectal Cancer After Preoperative Chemoradiotherapy: A Retrospective Analysis.

BACKGROUND/AIM: Previous evaluation of the safety and clinical efficacy of re-irradiation for pelvic recurrence of rectal cancer after preoperative chemoradiotherapy (PCRT) and rectal surgery is insufficient. We evaluated the safety and efficacy of re-irradiation with carbon-ion radiotherapy (C-ion RT) for pelvic recurrence of rectal cancer after PCRT. PATIENTS AND METHODS: We reviewed the medical records of patients treated with C-ion RT between August 2011 and December 2021 and analyzed the data of seven consecutive patients. The probabilities of overall survival (OS), local control (LC), and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Toxicities were classified using the National Cancer Institute's Common Terminology Criteria for Adverse Events (version 4.0). RESULTS: The median follow-up duration after C-ion RT initiation was 30.9 months. Five patients received 73.6 Gy [relative biological effectiveness (RBE)] in 16 fractions, and two patients received 57.6 Gy (RBE) in 12 fractions. All patients completed C-ion RT as scheduled. Two-year estimated OS, LC, and PFS rates after C-ion RT initiation were 100%, 83.3%, and 28.6%, respectively. No patients developed grade ≥3 acute toxicity. Regarding late toxicities, one patient who received Gore-Tex sheets as a spacer before C-ion RT developed grade 3 colon perforation, and then developed a grade 3 urinary tract disorder. One patient developed grade 2 peripheral neuropathy. CONCLUSION: C-Ion RT showed favorable local efficacy with minimal toxicity. C-Ion RT might be an effective treatment option for pelvic recurrence of rectal cancer after PCRT even when re-irradiation of the pelvis is required.

Long-term survivor of hepatocellular carcinoma treated with repeated carbon ion radiotherapy and transarterial chemoembolization: a case report.

Hepatocellular carcinoma (HCC) often recurs in the liver and requires multiple rounds of treatment. Thus, less-invasive multidisciplinary approaches are essential for preserving liver function, especially in elderly patients. Here, we report a case of an 86 year-old Japanese male patient with HCC who was successfully treated with repeated carbon ion radiotherapy (C-ion RT) and transarterial chemoembolization (TACE). The patient had alcoholic liver cirrhosis with a 60 mm HCC lesion and a satellite lesion in segment 6. The patient underwent initial C-ion RT but developed primary tumor recurrence (segment 6) and a new lesion (segment 2) 24 months later. The patient received TACE for each lesion, followed by an increased dose of C-ion RT for the recurrent primary tumor. Although the primary tumor lesion was well controlled, the patient subsequently developed new lesions, and TACE was repeated. The patient died of bacterial pneumonia 88 months after the initial treatment. His general condition and liver function were well preserved, and no severe adverse events were observed throughout the course of treatment. These results suggest that a less-invasive multidisciplinary approach involving repeated C-ion RT combined with TACE enables preservation of liver function, which may contribute to long-term survival in elderly patients with HCC.