Optimizing Therapeutic Approaches in Superficial Esophageal Cancer: Reduced-volume Radiotherapy and Dose-dense Chemotherapy After Endoscopic Resection.

BACKGROUND/AIM: Endoscopic submucosal dissection (ESD) followed by chemoradiotherapy (CRT) has become a promising treatment modality in the management of early-stage superficial esophageal squamous cell carcinoma (SESCC). However, radiotherapy often leads to significant adverse events (AEs), including cardiopulmonary toxicity, limiting the delivery of this treatment modality. This study aimed to evaluate the efficacy of reduced-volume radiotherapy and dose-dense chemotherapy in mitigating AEs for high-risk SESCC following ESD. PATIENTS AND METHODS: We retrospectively analyzed patients treated with customized CRT after ESD between 2014 and 2023. RESULTS: Thirty-nine consecutive patients were identified. The median follow-up period was 63.4 months (range=8.3-99.8 months). All patients completed CRT, with a low incidence (3%) of grade ≥3 nonhematologic AEs. Thirteen patients (33%) had a recurrence: 10 local, one regional, and two distant. The 5-year overall and disease-free survival rates were 77% and 64%, respectively. A positive vertical resection margin was identified as a prognostic factor associated with survival. CONCLUSION: Our novel approach of combining ESD with customized reduced-volume radiotherapy and dose-dense chemotherapy shows promise in providing favorable oncologic outcomes and a safer nonsurgical strategy for high-risk SESCC. Specifically, this regimen minimized cardiopulmonary toxicity without compromising therapeutic efficacy. More aggressive adjuvant therapy may be required for patients with positive vertical resection margins after ESD.

The Feasibility of Omission of Postoperative Radiotherapy in Japanese Patients With Early Breast Cancer Treated With Breast-Conserving Surgery.

Background This study was aimed at analyzing the impact of postoperative radiotherapy (PORT) after breast-conserving surgery (BCS) on Japanese patients with early-stage breast cancer and exploring the potential of PORT omission. Materials and methods Data from 794 patients with early-stage breast cancer (T1-2, N0-1), who underwent BCS with (n = 310) or without PORT (n = 484) were retrospectively analyzed. Local control (LC) rate and breast cancer-specific survival (BCSS) were compared between the groups that received and did not receive PORT in the whole cohort and low-risk cohort (i.e., the cohort with negative surgical margin, lymph node negativity, and estrogen receptor positivity, excluding young age of 49 or less), and in low-risk subgroup using propensity-score matching. Results PORT was associated with better LC but not BCSS in the total population. In the low-risk cohort, the incidence of local recurrence in patients without and with PORT was 5.3% and 4.8%, respectively, at 10 years (p = 0.591), and 7.8% and 4.8%, respectively, according to propensity-score matching (p = 0.485). Conclusion PORT improved LC in the total population, but not BCSS or overall survival (OS). In the low-risk group analysis (negative surgical margin, lymph node negativity, estrogen receptor positivity, and age 50 years or more), equivalent LC, BCSS, and OS were found including propensity-matched comparison. Therefore, this study showed that the omission of PORT could be a treatment option for low-risk Japanese patients. Further multi-center prospective studies are warranted to validate these findings and reduce the unnecessary burden of PORT for patients and institutions.

The influence of Gleason score ≤ 6 histology on the outcome of high-risk localized prostate cancer after modern radiotherapy.

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

Albumin-bilirubin score is a useful predictor of worsening liver reserve after stereotactic body radiation therapy in elderly Japanese patients with hepatocellular carcinoma.

The prognosis of patients with hepatocellular carcinoma (HCC) is closely related to their liver reserves. The Child-Pugh (CP) score has traditionally been used to evaluate this reserve, with CP Grade B (CP score ≥ 7) associated with a higher risk of radiation-induced liver disease after stereotactic body radiation therapy (SBRT). However, the CP score has limitations, as it does not accurately assess liver reserve capacity. The albumin-bilirubin (ALBI) score has been introduced as a meticulous indicator of liver reserve for the treatment of HCC. We retrospectively evaluated the role of the ALBI score in estimating the worsening liver reserve in 42 patients with HCC treated with SBRT using CyberKnife between 2015 and 2023. The median biologically effective dose (α/ß = 10 Gy) was 100 Gy. For a median follow-up duration of 17.4 months, the 1-year overall survival (OS), local control (LC) and progression-free survival (PFS) rates were 100, 98 and 62%, respectively. Worsening liver reserve was defined as an increase in the modified ALBI grade or CP score within 1 year after SBRT. Univariate and multivariate analyses showed that the baseline ALBI score (≥-2.7 vs <-2.7) was the only significantly different predictor of worsening liver reserve. The OS and LC rates after SBRT for HCC were satisfactory. However, the PFS was poor, and recurrent HCC will require additional treatment. It is clinically important to predict the liver reserve capacity after SBRT, and the baseline ALBI score is a useful predictor.

Comparative dosimetric study of spot-scanning proton therapy versus volumetric-modulated radiation therapy for extrahepatic bile duct cancer.

This study aimed to compare the dose distributions and clarify the dosimetric characteristics of spot-scanning proton therapy (SSPT) and photon volumetric modulated arc therapy (VMAT) for extrahepatic bile duct cancer (EBDC). This retrospective study included 10 patients with EBDC treated with real-time image-gated SSPT. Using the simultaneous integrated boost technique, the 2 prescription dose levels for planning target volumes were 72.6 and 44 Gy, delivered in 22 fractions. Plan quality comparisons were conducted by analyzing various parameters, including homogeneity, conformity, dose to organs at risk, and normal tissue complication probability (NTCP) for radiation-induced liver damage (RILD). The target dose distributions using SSPT were almost equivalent to those achieved using photon VMAT. There was a significant reduction in all liver dose parameters, the NTCP value for RILD, and kidney dose (mean, V12 Gy, and V18 Gy) in SSPT than in photon VMAT. No significant differences were observed in the intestinal doses in the high-dose area. Thus, compared with photon VMAT, SSPT for EBDC significantly reduced radiation doses to the liver and kidneys and has shown potential clinical benefits of reduced radiation-induced toxicity.

The Feasibility of Omitting Postoperative Radiotherapy in Japanese Patients With Ductal Carcinoma In Situ of Breast Treated With Breast-Conserving Surgery.

Background To analyze the feasibility of omitting postoperative radiotherapy (PORT) after breast-conserving surgery (BCS) in Japanese patients with ductal carcinoma in situ (DCIS). Materials and methods We retrospectively analyzed 88 patients with small pure DCIS (median diameter 1.1 cm, ≤ 4 cm) who underwent BCS with (n = 39) or without (n = 49) PORT. The primary and secondary endpoints were ipsilateral breast tumor recurrence (IBTR) and overall survival (OS), respectively, between the groups that received PORT and those that did not. Results The PORT group included a high number of margin-positive cases. The incidence of IBTR was 2.4% (95% confidence interval (CI), 0.3-15.7%) and 2.8% (95% CI, 0.4-18.2%) at five years and 5.5% (95% CI, 1.4-20.6%) and 2.8% (95% CI, 0.4-18.2%) at 10 years in patients without and with PORT, respectively (p = 0.686). In the margin-negative group, only one patient showed IBTR without RT (2.3%), whereas no patient with PORT experienced IBTR (0%). To date, there have been no regional or distant metastases; therefore, no patient has experienced breast cancer-related deaths. The OS rates were 97.7% (95% CI, 84.9-99.6%) and 100% at 10 years in patients without and with PORT, respectively (p = 0.372). Conclusion This study suggests that the omission of PORT after BCS could be a feasible option for selected Japanese patients but requires further investigation to identify the low-risk factor in patients who can omit PORT.

Increasing rectum-prostate distance using a hydrogel spacer to reduce radiation exposure during proton beam therapy for prostate cancer.

SpaceOAR, a polyethylene-glycol hydrogel, reduces rectal radiation exposure during radiation therapy for prostate cancer. Previously, our group reported the modified technique of hydrogel insertion, which achieves greater separated distance at prostate-apex. This study aimed to investigate the impact of separated distance at prostate-apex and our modifier technique, on radiation exposure reduction during proton beam therapy (PBT). We included 330 patients undergoing PBT with the relative biological effectiveness (RBE) of 63 Gray (Gy) for localized prostate cancer, and categorized them into groups 0 (no spacer, n = 141), 1 (separated distance of spacer at the prostate-apex level < 7.5 mm, n = 81), and 2 (distance ≥ 7.5 mm, n = 108). The rectal volumes to receive 30-60 Gy (RBE), was estimated and described as Rectal V30-60 (ml) in 10 Gy increments. The Rectal V30-60 (ml) was significantly lower in group 2 than in group 1, and in group 1 than in group 0. After propensity score matching, the multivariate logistic regression analysis revealed that the most significant factor to reduce radiation exposure was our modified technique of hydrogel insertion. Therefore, using a hydrogel spacer to expand the prostate-rectum distance not only at prostate-mid to prostate-base level but also at the prostate-apex level can reduce the radiation exposure in PBT for prostate cancer.

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.

Analysis of particle therapy registries based on a unified treatment policy for esophageal cancer.

This study aimed to evaluate the efficacy and safety of particle therapy (proton beam therapy and carbon-ion radiotherapy) for esophageal cancer by analyzing prospective nationwide registry data from particle therapy facilities throughout Japan. Patients diagnosed with esophageal cancer who received particle therapy between May 2016 and June 2018 were recruited from the registries of 12 particle therapy centers in Japan. Eventually, we enrolled 174 patients who met the inclusion criteria. Of the 174 patients, 137 (78.7%) were male, with a median age of 69 years (range: 41-88 years). Clinical stages included I (n = 55; 31.6%), II (n = 31; 17.8%), III (n = 82; 47.1%), IV (n = 3; 1.7%) and unknown (n = 3; 1.7%) (Union for International Cancer Control, seventh edition), and the median follow-up period was 908 days (range: 76-1669 days) for all patients. The 3-year overall survival (OS) rate, the 3-year progression-free survival (PFS) rate and the 3-year local control (LC) rates were 60.5, 53.2 and 72.7%, respectively. For each clinical stage, the 3-year OS rates were I, 84.8%; II, 60.3% and III, 42.9%; the 3-year PFS rates were I, 71.9%; II, 58.3% and III, 37.0% and the 3-year LC were I, 78.4%; II, 79.8% and III, 65.2%, respectively. Notably, four patients (2.3%) with ≥Grade 3 cardiopulmonary toxicities were observed (Common Terminology Criteria for Adverse Events, version 5.0). Our study showed that particle therapy for esophageal cancer has lower rates of adverse cardiopulmonary events than X-ray radiotherapy.

Particle beam therapy versus photon radiotherapy for extrahepatic biliary cancer-systemic review and meta-analysis.

Particle beam therapy (PT) is a potentially promising approach to the treatment of extrahepatic biliary cancer (EBC) because of its unique dose distribution using the Bragg peak. However, the superiority of PT to photon radiotherapy (XT) remains unclear. Therefore, we conducted a systematic review and meta-analysis to compare PT and XT for the treatment of EBC. The primary endpoint was overall survival (OS), which was pooled using a random-effects model. Nine articles comprising a total of 1558 patients (seven XT articles, n = 1488 patients; two PT articles, n = 70 patients) were screened. In addition, we compared the outcomes of XT and PT with the outcomes available from a prospective data registry (proton-net). The 1-year OS probability rates were 55, 65 and 72% for the XT group, PT group and PT registry, respectively. The 2-year OS probability rates were 26, 38 and 38% for the XT group, PT group and PT registry, respectively. The 3-year OS probability rates were 12, 35 and 18% for the XT group, PT group and PT registry, respectively. Although the difference between the 1-year OS rates of the XT group and PT registry was statistically significant, no other significant superiority was observed among these groups. In conclusion, the efficacy of PT was not superior to that of XT during this meta-analysis.

Particle beam therapy for pelvic recurrence of colorectal cancer: a registry data analysis in Japan and a systematic review.

The aim of this study was to investigate the efficacy and safety of particle beam therapy (PBT) with proton or carbon ion beam for pelvic recurrence of colorectal cancer (PRCC) by comparing the clinical outcomes of a dataset of prospectively enrolled patients for PBT with those from the literature, which were collected by a systematic review of external X-ray radiotherapy (XRT) and PBT. Patients with PRCC treated at 14 domestic facilities between May 2016 and June 2019 and entered the database for prospective observational follow-up were analyzed. The registry data analyzed included 159 PRCC patients treated with PBT of whom 126 (79%) were treated with carbon ion radiation therapy (CIRT). The 3-year overall survival and local control rate were 81.8 and 76.4%, respectively. Among these PRCC patients, 5.7% had Grade 3 or higher toxicity. Systematic search of PubMed and Cochrane databases published from January 2000 to September 2020 resulted in 409 abstracts for the primary selection. Twelve studies fulfilled the inclusion criteria. With one additional publication, 13 studies were selected for qualitative analysis, including 9 on XRT and 4 on PBT. There were nine XRT studies, which included six on 3D conformal radiotherapy and three on stereotactic body radiation therapy, and four PBT studies included three on CIRT and one on proton therapy. A pilot meta-analysis using literatures with median survival time extractable over a 20-month observation period suggested that PBT, especially CIRT, may be a promising treatment option for PRCC not amenable to curative resection.

Potential benefit of dose-escalated stereotactic body radiation therapy using CyberKnife for early-stage primary lung cancer.

INTRODUCTION: The study aimed to evaluate the efficacy and safety of dose-escalated stereotactic body radiotherapy (SBRT) for primary lung cancer. METHODS: Patients with peripherally located T1-2N0M0 primary lung cancer who underwent SBRT from April 2013 to December 2019 were included. Group A received 60 Gy in five fractions with CyberKnife prescribed at 99% gross tumor volume. Group B received 48 Gy in four fractions by a gantry-mounted linear accelerator, with isocenter prescription. Cumulative incidence of local failure (LF), progression free survival (PFS), overall survival (OS), and toxicity were retrospectively compared. RESULTS: Groups A and B comprised 39 and 36 patients, respectively. Group A had more patients without histological confirmation (p < .001) and showed lower V20 of bilateral lungs (p = .025). The median follow-up duration of Group A and B was 22.0 and 21.5 months, respectively, and the 2-year cumulative incidence of LF, PFS, and OS were .0% versus 11.6% (p = .065), 66.2% versus 62.7% (p = .694), 84.1% versus 81.1% (p = .827), respectively. There was no difference in Grade ≥ 2 toxicity rate between Groups A and B (7.7% vs. 11.1%; p = .704). CONCLUSION: Dose-escalated SBRT using CyberKnife showed reduced lung dose and potential benefits for improved local control with comparable toxicity.

Particle Beam Therapy for Intrahepatic and Extrahepatic Biliary Duct Carcinoma: A Multi-Institutional Retrospective Data Analysis.

To examine the efficacy and toxicity of particle beam therapy (PT) for biliary duct carcinoma (BDC) and compare the outcomes between extrahepatic BDC (eBDC) and intrahepatic BDC (iBDC). We analyzed multi-institutional data from May 2009 to December 2019. The primary endpoint was overall survival (OS), and the secondary endpoints were local control (LC), progression-free survival (PFS) and toxicity. We included 150 patients with unresectable BDC treated with PT using a median prescribed dose of 70.2 GyRBE (range, 44-77 GyRBE) in 25 fractions (range, 10-38 fractions). With a median follow-up of 13.0 months, median survival time (MST) was 21 months, and 2-year OS was 44.8%. For eBDC and iBDC, the MSTs were 20 and 23 months, respectively. Two-year PFS and LC rates were 20.6% and 66.5%, respectively. Vascular invasion, prescribed dose and serum tumor marker level (carcinoembryonic antigen: CEA) were identified as poor prognostic factors for OS. A higher radiation dose EQD2 ≥ 67 Gy showed superior OS, with a hazard ratio of 0.341. The radiation dose of PT is an important predisposing factor for overall survival. The MST for patients with eBDC given a higher radiation dose was 25 months, compared to 15 months for those given the lower dose and 23 months for patients with iBDC (all iBDC given higher doses). iBDC and eBDC duct carcinomas showed equivalent outcomes with PT, especially when treated with a high radiation dose. In detailed analysis, baseline CEA level in iBDC, and radiation dose and GTV in eBDC were statistically significant predicators for OS. Acute and late toxicity grade ≥3 occurred in 2.2% and 2.7% of patients, respectively, including two late grade-5 toxicities. In conclusion, PT showed good efficacy for BDC, both eBDC and iBDC, with a low incidence of severe toxicity.

Chemoradiation versus surgery for superficial esophageal squamous cell carcinoma after noncurative endoscopic submucosal dissection: comparison of long-term oncologic outcomes.

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

Palliative Radiation Therapy for Intramedullary Spinal Cord Metastasis.

BACKGROUND/AIM: The purpose of this study was to retrospectively review the outcomes of intramedullary spinal cord metastasis (ISCM) and identify predictors for ambulation after radiotherapy (RT). PATIENTS AND METHODS: We analyzed 16 lesions in 15 patients treated with RT for ISCM at our clinic from October 2009 to April 2020 to evaluate predictors for improved ambulation following RT. RESULTS: The primary diseases included nine cases of lung cancer, two cases of breast cancer, and several others. The RT schedule was primarily 30 Gy/10 fractions in seven cases, while others were applied to nine cases. The median overall survival time was 99 days. After RT, all seven patients who could walk prior to RT were still able to walk (100%), whereas only two of nine patients who could not walk prior to RT were able to walk (22%, p=0.004). CONCLUSION: Ambulation prior to RT was a significant predictor of ambulation ability after RT.

＜Editors' Choice＞ Elective nodal irradiation versus involved field radiotherapy for limited disease small cell lung cancer: a single-institution experience.

Elective nodal irradiation (ENI) and involved field radiotherapy (IFRT) are definitive radiotherapeutic approaches used to treat patients with limited-disease small cell lung cancer (LD-SCLC). However, no solid consensus exists on their optimal target volume. The current study aimed to assess the clinical outcomes of patients with LD-SCLC who received definitive ENI or IFRT. A retrospective single-institution study of patients who received definitive radiotherapy between 2008 and 2020 was performed. All patients underwent whole-body positron emission tomography/computed tomography before three-dimensional conformal radiotherapy. Among the 37 patients analyzed, 22 and 15 received ENI and IFRT, respectively. The thoracic radiotherapy dose was mostly either 60 Gy in 30 fractions delivered in 2-Gy fractions once daily or 45 Gy in 30 fractions delivered in 1.5-Gy fractions twice daily. The median follow-up period was 21.4 months. A total of 12 patients (32%) experienced locoregional relapse: 10 within and 2 outside the irradiation fields. One patient in the IFRT group experienced isolated nodal failure. Differences in locoregional relapse-free, progression-free, and overall survival rates between ENI and IFRT were not significant. Overall, IFRT did not promote a significant increase in locoregional recurrence compared to ENI. Our findings suggested the utility of IFRT in standard clinical practice and support its use for patients with LD-SCLC.

Role of Brachytherapy Boost in Clinically Localized Intermediate and High-Risk Prostate Cancer: Lack of Benefit in Patients with Very High-Risk Factors T3b-4 and/or Gleason 9-10.

This study examined the role of brachytherapy boost (BT-boost) and external beam radiotherapy (EBRT) in intermediate- to high-risk prostate cancer, especially in patients with very high-risk factors (VHR: T3b-4 or Gleason score 9-10) as patients with double very high-risk factors (VHR-2: T3b-4 and Gleason score 9-10) previously showed worst prognosis in localized prostate cancer. We retrospectively reviewed multi-institutional data of 1961 patients that were administered radiotherapy (1091 BT-boost and 872 EBRT: 593 conventional-dose RT (Conv RT: equivalent to doses of 2 Gy per fraction = EQD2 ≤ 72 Gy) and 216 dose-escalating RT (DeRT = EQD2 ≥ 74 Gy). We found that BT-boost improved PSA control and provided an equivalent overall survival rate in the intermediate- and high-risk groups, except for patients within the VHR factor group. In the VHR-1 group (single VHR), BT-boost showed a superior biochemical control rate to the Conv RT group but not to the DeRT group. In the VHR-2 group, BT-boost did not improve outcomes of either Conv RT or DeRT groups. In conclusion, BT-boost showed no benefit to modern DeRT in the patients with VHR; therefore, they are not good candidates for BT-boost to improve outcome and may be amenable to clinical trials using multimodal intensified systemic treatments.

Repeated Stereotactic Body Radiotherapy for Lung Malignancies: Toxicity Can Be Reduced by Sparing Lung Irradiation.

BACKGROUND/AIM: Evidence on the use of repeated stereotactic body radiotherapy (SBRT) is limited. We investigated the efficacy of repeated SBRT and predictors of lung toxicity. PATIENTS AND METHODS: We reviewed 20 patients (27 lesions) with primary or metastatic lung cancer who underwent repeated SBRT with CyberKnife® We generated a composite plan for dosimetric analysis based on equivalent doses in 2.0-Gy fractions (α/ß=3). Predictors of Grade 2+ radiation pneumonitis (RP) were examined. RESULTS: The median follow-up duration was 18.0 months. The 1-year and 2-year local control were both 95.2%. Five patients (25%) developed Grade 2+ RP, including a Grade 5 RP. The Grade 2+ RP group showed higher composite mean lung dose (MLD) and lower lung volumes spared from 5-20 Gy (VS5-VS20). CONCLUSION: Repeated SBRT with CyberKnife® showed favorable local control, but a high rate of Grade 2+ RP. Accumulated MLD and VS5-VS20 may predict RP.

Comparison of toxicities between ultrahypofractionated radiotherapy versus brachytherapy with or without external beam radiotherapy for clinically localized prostate cancer.

To compare gastrointestinal (GI) and genitourinary (GU) toxicities in patients with localized prostate cancer treated with ultrahypofractionated radiotherapy (UHF) or brachytherapy [BT; low dose rate, LDR or high dose rate (HDR) with or without external beam radiotherapy (EBRT)]. We compared 253 UHF and 1664 BT ± EBRT groups. The main outcomes were the incidence and severity of acute and late GU and GI toxicities. The secondary endpoint was biochemical control rate. Cumulative late actuarial GU toxicity did not differ for grade ≥ 2 (8.6% at 5-years in UHF and 13.3% in BT ± EBRT, hazard ratio [HR], 0.7066; 95% CI, 0.4093-1.22, p = 0.2127). Actuarial grade ≥ 2 late GI toxicity was higher in UHF (5.8% at 5-years, HR: 3.619; 95% CI, 1.774-7.383, p < 0.001) than in BT ± EBRT (1.1%). In detailed subgroup analyses, the high-dose UHF group (H-UHF) using BED ≥ 226 Gy1.5, showed higher GI toxicity profiles than the other subgroups (HDR + EBRT, LDR + EBRT, and LDR monotherapy, and L-UHF BED < 226 Gy1.5) with equivalent GU toxicity to other modalities. With a median follow-up period of 32 months and 75 months, the actuarial biochemical control rates were equivalent between the UHF and BT ± EBRT groups. UHF showed equivalent efficacy, higher GI and equivalent GU accumulated toxicity to BT ± EBRT, and the toxicity of UHF was largely dependent on the UHF schedule.

Conventional dose versus dose escalated radiotherapy including high-dose-rate brachytherapy boost for patients with Gleason score 9-10 clinical localized prostate cancer.

As several recent researches focus on the importance of Gleason 9-10, we examine the role of radiotherapy dose escalation in those patients. We analyzed 476 patients with Gleason score 9-10 prostate cancer treated with radiotherapy. Of them, 127 patients were treated with conventional-dose external beam radiotherapy (Conv RT) and 349 patients were treated with high-dose radiotherapy (HDRT; 249 patients received high-dose-rate brachytherapy boost + external beam radiotherapy [HDR boost] and 100 patients received intensity-modulated radiotherapy [IMRT]). We compared these treatment groups using multi-institutional retrospective data. The patients had a median follow-up period of 66.3 months. HDRT showed superior biochemical disease-free survival (bDFS) rate (85.2%; HDR boost 84.7% and IMRT 86.6%) to Conv RT (71.1%, p < 0.0001) at 5 years, with a hazard ratio of 0.448. There were borderline difference in prostate cancer-specific mortality (PCSM; 4.3% and 2.75%, p = 0.0581), and distant metastasis-free survival (DMFS; 94.4% and 89.6%, p = 0.0916) rates at 5-years between Conv RT and HDRT group. Dose escalated radiotherapy showed better bDFS, borderline improvement in PCSM, and equivocal outcome in DMFS in with clinically localized Gleason 9-10 prostate cancer.