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Management of pelvic node-positive prostate cancer has been challenging and controversial. We conducted a study to evaluate the outcomes of whole-pelvic (WP) simultaneous integrated boost (SIB) intensity-modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT).A total of 67 consecutive patients with cT1c-4N1M0 prostate cancer were definitively treated by WP SIB-IMRT. Neoadjuvant ADT (median: 8.3 months) was administered in all cases. WP SIB-IMRT was designed to simultaneously deliver 78, 66.3, and 58.5 Gy in 39 fractions to the prostate plus seminal vesicles, metastatic lymph nodes (LNs), and the pelvic LN region, respectively. Adjuvant ADT (median: 24.7 months) was administered in 66 patients.The median follow-up period was 81.6 months (range: 30.5-160.7). Biochemical relapse-free, overall, and prostate cancer-specific survival rates at 10 years were 59.8%, 79.6%, and 86.3%, respectively. Loco-regional recurrence was not observed. Being in International Society of Urological Pathology grade group 5 and having a posttreatment detectable nadir prostate-specific antigen (PSA) level (≥0.010 ng/ml) were significantly associated with worse prostate cancer-specific survival and progression of castration resistance. The 10-year cumulative incidence rates of grade 2 and 3 late toxicities were, respectively, 1.5% and 0% for genitourinary, 0% and 1.5% for gastrointestinal events. No grade 4 acute or late toxicities were observed.WP SIB-IMRT can be safely administered to patients with pelvic node-positive prostate cancer. Since grade group 5 and detectable nadir PSA levels are risks for castration resistance, we may need to increase the intensity of treatment for such cases.

The aim of this study was to evaluate the effects of treatment with both three-dimensional radiotherapy (3DRT) and weekly 40-mg/m2 cisplatin on postoperative uterine cervical cancer patients with high-risk prognostic factors. We conducted a retrospective multi-institutional chart review of postoperative uterine cervical cancer patients with high-risk prognostic factors who had been treated with both 3DRT and weekly 40-mg/m2 cisplatin from 2007 to 2012. Each participating hospital provided detailed information regarding patient characteristics, treatment outcomes, and treatment complications. The eligible 96 patients were analyzed. The median follow-up period was 61 months. The 3-year relapse-free survival, overall survival (OS), and locoregional relapse-free survival (LRFS) rates were 76%, 90%, and 88%, respectively. In multivariate analysis, the histological finding of either adenocarcinoma or adenosquamous carcinoma was a significant risk factor for both OS and LRFS. The percentage of patients with grade ≥ 3 acute hematologic toxicity, acute lower gastrointestinal toxicity (GIT), and late lower GIT were 45%, 19%, and 17%, respectively. The outcomes of concurrent chemoradiotherapy (CCRT) using weekly 40-mg/m2 cisplatin are similar to those in the previous studies that used several chemotherapy regimens. However, postoperative CCRT using 3DRT had a high level of late GIT.

The purpose of this pilot study was to evaluate the feasibility of highly hypofractionated intensity-modulated radiation therapy (IMRT) in 15 fractions over 3 weeks for treating localized prostate cancer based on prostate position-based image-guided radiation therapy. Twenty-five patients with National Comprehensive Cancer Network (NCCN) very low- to unfavorable intermediate-risk prostate cancer were enrolled in this study from April 2014 to September 2015 to receive highly hypofractionated IMRT (without intraprostatic fiducial markers) delivering 54 Gy in 15 fractions over 3 weeks. Patients with intermediate-risk disease underwent neoadjuvant androgen suppression for 4-8 months. Twenty-four patients were treated with highly hypofractionated IMRT, and one was treated with conventionally fractionated IMRT because the dose constraint of the small bowel seemed difficult to achieve during the simulation. Seventeen percent had very low- or low-risk, 42% had favorable intermediate-risk, and 42% had unfavorable intermediate-risk disease according to NCCN guidelines. The median follow-up period was 31 months (range, 24-42 months). No Grade ≥3 acute toxicity was observed, and the incidence rates of Grade 2 acute genitourinary and gastrointestinal toxicities were 21% and 4%, respectively. No Grade ≥2 late toxicity was observed. Biochemical relapse was observed in one patient at 15 months, and the biochemical relapse-free survival rate was 95.8% at 2 years. A prostate-specific antigen bounce of ≥0.4 ng/ml was observed in 11 patients (46%). The highly hypofractionated IMRT regimen is feasible in patients with localized prostate cancer and is more convenient than conventionally fractionated schedules for patients and health-care providers.

259 Background: A number of reports have been published on both moderately hypofractionated intensity-modulated radiation therapy (IMRT) for localized prostate cancers using 2.4 – 3.4 Gy per fraction over 4 – 6 weeks, and ultrahypofractionation over 1 – 2 weeks using 6 Gy or more per fraction. However, long-term outcomes have sparsely been reported using doses between these two fractionations (3.4 – 6.0 Gy per fraction) over 2 – 3 weeks (high hypofractionation). Therefore, we performed a pilot study of highly hypofractionated IMRT in 15 fractions using 3.6 Gy per fraction over 3 weeks for localized prostate cancer. We now report the long-term outcomes of the study. Methods: Twenty-five patients with low- to intermediate-risk prostate cancer were enrolled in this prospective study from April 2014 to September 2015. Fifty-four Gy in 15 fractions (3.6 Gy per fraction) was delivered over three weeks using IMRT with CBCT-based image guidance without intraprostatic fiducial markers. Based on an estimated alpha/beta ratio for prostate cancer of 1.5 Gy, the EQD2 was 78.7 Gy for the present dose fractionation. Neoadjuvant hormonal therapy (HT) was administered to intermediate-risk patients for 4 – 8 months, but was not mandatory in patients with low-risk disease. Adjuvant HT was not provided for any patient. Biochemical relapse-free survival (BRFS), clinical relapse-free survival (CRFS), overall survival (OS), and the cumulative incidence rate of late toxicities were analyzed using the Kaplan Meier method. Results: Twenty-four patients were treated with highly hypofractionated IMRT, except one case switched to conventionally fractionated IMRT because we could not meet the dose constraint of the small bowel in treatment planning. Among the 24 patients, 17 % had low-risk, and 83% had intermediate-risk disease. Neoadjuvant HT was administered to 23 patients, and the median duration of HT was 5.3 months. The median follow-up period was 77 months (range, 57–87 months). BRFS, CRFS, and OS were 91.7%, 95.8% and 95.8% at 5 years, and 87.5%, 86.3% and 95.8% at 7 years, respectively. No patient died of prostate cancer, but one patient died due to the other cancer. Neither grade ≥2 late gastrointestinal toxicity nor ≥3 late genitourinary toxicity was observed. Grade 2 late genitourinary toxicity did not occur during the first 4 years, but was developed in 5 patients after more than 4-year follow-up. The cumulative incidence rate was 12.9% and 22.8% at 5 and 7 years, respectively. Conclusions: Highly hypofractionated IMRT delivering 54 Gy in 15 fractions over 3 weeks for prostate cancer without intraprostatic fiducial markers demonstrates favorable oncological outcomes with no severe complications. This treatment approach could be a possible alternative of moderate hypofractionation, although further studies will be mandatory.

441 Background: Dynamic tumor-tracking (DTT) stereotactic body radiotherapy (SBRT) with real-time monitoring for liver tumors using a gimbal-mounted linac can decrease the normal liver dose and planning target volume (PTV) without sacrificing the target dose. We hypothesized that this method would yield excellent tumor control comparable to that by the conventional SBRT. We conducted a multi-institutional prospective phase II study to evaluate the safety and efficacy of DTT-SBRT for liver tumors (UMIN-CTR, UMIN000017886). Methods: The main eligibility criteria were as follows: (1) < 4 liver tumors; (2) technical difficulties with percutaneous ablation therapies, inoperable lesions, or patient refusal to undergo surgery; (3) Eastern Cooperative Oncology Group performance status of 0–2; (4) Child-Pugh score of ≤8; and (5) respiratory motion of ≥10 mm. The primary endpoint was the local control rate (LC) at 2 years (expected endpoint: > 90%), and the secondary endpoints were overall survival rate (OS), progression-free survival rate (PFS), and treatment-related toxicity. We performed DTT-SBRT with 40 Gy in 5 fractions prescribed to the PTV D95, and a maximum dose of 55−58 Gy using 7–9 static non-coplanar ports of the 6-MV beam was applied. The Kaplan-Meier analysis was performed to estimate the OS and LC. Treatment-related toxicity was scored according to the Common Terminology Criteria for Adverse Events v.4.0. Results: Forty-eight patients (48 tumors) were registered from four institutes and successfully treated between September 2015 and March 2019. Their median age was 74 years (range, 52–97). Thirty-nine tumors were hepatocellular carcinomas, and nine were metastatic liver tumors. The median tumor size was 5.8 ml (range, 0.7–64.1). At the time of data cutoff on March 31, 2021, the median follow-up period was 36.5 months (range, 3.0–62.4). The 2-year LC was 98.0%. Two-year OS and PFS were 88.8% and 55.1%, respectively. Recurrences were observed in 33 patients (68.5%). One patient (0.2%) had local recurrence, 30 (62.5%) developed new hepatic lesions outside of the irradiation field, and 9 (18.8%) had distant metastases. Grade 3 adverse events were observed in seven patients, including elevation of liver or biliary enzyme levels and hematopoietic adverse events. No treatment-related toxicity of grade 4 or higher was observed. Conclusions: Employing DTT-SBRT to treat liver tumors resulted in excellent LC with acceptable incidence of adverse events. This method will be a promising alternative therapy for patients who cannot receive surgery or percutaneous ablation therapy. To the best of our knowledge, this is the first phase II trial evaluating DTT-SBRT for liver tumors. Clinical trial information: UMIN000017886.

Highlights • High-dose prostate IMRT was well tolerated in terms of long-term GU toxicities. • Hematuria was the most common long-term GU toxicity after high-dose IMRT. • Bladder neck dose–volume data were significantly associated with hematuria., Purpose To investigate the factors associated with the risk of long-term genitourinary (GU) toxicity among high-risk prostate cancer (PC) patients treated with high-dose intensity-modulated radiotherapy (IMRT). Methods and materials Between 2000 and 2011, PC patients treated with 78 Gy in 39 fractions delivered by IMRT combined with neo-adjuvant hormonal therapy were selected from among our database. GU toxicities and clinical factors, as well as separate anatomical urinary structures, were evaluated in terms of their associations. Results A total of 309 patients was included in this study. The median follow-up was 104 months (range: 24–143 months). The most frequently observed late grade ≥2 GU toxicity was hematuria (11.2%: 10-year actuarial risk) with radiation cystitis observed in the majority of patients. In univariate analysis, late grade ≥2 hematuria was associated with the exposure to doses >75 Gy (V75) of the bladder neck and V70 of the bladder wall, as well as with T stage. V75 of the bladder neck remained significant in multivariate analysis (p = 0.049). Conclusions At the 10-year follow up of high-dose IMRT, a major concern was proved to be delayed cystitis related to the higher volume of bladder neck dose exposed excess over 75 Gy.

The aim of this study was to evaluate the effects of treatment with both three-dimensional radiotherapy (3DRT) and weekly 40-mg/mWe conducted a retrospective multi-institutional chart review of postoperative uterine cervical cancer patients with high-risk prognostic factors who had been treated with both 3DRT and weekly 40-mg/mThe eligible 96 patients were analyzed. The median follow-up period was 61 months. The 3-year relapse-free survival, overall survival (OS), and locoregional relapse-free survival (LRFS) rates were 76%, 90%, and 88%, respectively. In multivariate analysis, the histological finding of either adenocarcinoma or adenosquamous carcinoma was a significant risk factor for both OS and LRFS. The percentage of patients with grade ≥ 3 acute hematologic toxicity, acute lower gastrointestinal toxicity (GIT), and late lower GIT were 45%, 19%, and 17%, respectively.The outcomes of concurrent chemoradiotherapy (CCRT) using weekly 40-mg/m

We aimed to analyze the 10-year outcomes of intensity-modulated radiation therapy (IMRT) combined with neoadjuvant hormonal therapy (HT) for patients with intermediate- and high-risk T1c-T2N0M0 prostate cancer. Fifty patients with T1c-T2N0M0 prostate cancer, who were treated with high-dose IMRT combined with neoadjuvant HT, were evaluated. Of these patients, 19 and 31 were classified into the intermediate- and high-risk groups, respectively. Neoadjuvant HT was administered over a median duration of 6 months; 74 and 78 Gy in 2 Gy per fraction were essentially delivered to the intermediate- and high-risk cases, respectively. Adjuvant HT was not administered to any of the patients after the completion of IMRT. Over a median follow-up period of 118 months, the 10-year prostate-specific antigen failure-free survival, prostate-specific antigen failure-free, salvage hormonal therapy-free, prostate cancer-specific survival, and overall survival rates were 70.2 %, 78.7 %, 89.2 %, 100 %, and 88.8 %, respectively. No grade 3 or higher acute or late toxicities were observed. The 10-year likelihoods of developing grade 2 late urinary and rectal toxicities were 13.7 % and 4.2 %, respectively. Compared with the outcomes of a cohort of historical controls who were locally irradiated with 70 Gy by three-dimensional conformal radiotherapy, the prostate-specific antigen failure-free rate was significantly better in the IMRT groups (78.7 % vs. 53.4 % at 10 years; p = 0.027). High-dose IMRT combined with neoadjuvant HT achieved not only high prostate-specific antigen control, but also excellent survival outcomes with acceptable morbidities, for a Japanese cohort of intermediate- and high-risk T1c-T2N0M0 prostate cancer patients, and these results warrant further investigation.

In this study, we assessed the differences in the dose distribution of a 4 MV photon beam among different calculation algorithms: the Acuros XB (AXB) algorithm, the analytic anisotropic algorithm (AAA), and the pencil beam convolution (PBC) algorithm (ver. 11.0.31), in phantoms and in clinical intensity‐modulated radiation therapy (IMRT) plans. Homogeneous and heterogeneous, including middle‐, low‐, and high‐density, phantoms were combined to assess the percentage depth dose and lateral dose profiles among AXB, AAA, and PBC. For the phantom containing the low‐density area, AXB was in agreement with measurement within 0.5%, while the greatest differences between the AAA and PBC calculations and measurement were 2.7% and 3.6%, respectively. AXB showed agreement with measurement within 2.5% at the high‐density area, while AAA and PBC overestimated the dose by more than 4.5% and 4.0%, respectively. Furthermore, 15 IMRT plans, calculated using AXB, for oropharyngeal, hypopharyngeal, and laryngeal carcinomas were analyzed. The dose prescription was 70 Gy to 50% of the planning target volume (PVT70). Subsequently, each plan was recalculated using AAA and PBC while maintaining the AXB‐calculated monitor units, leaf motion, and beam arrangement. Additionally, nine hypopharyngeal and laryngeal cancer patients were analyzed in terms of PTV70 for cartilaginous structures (PVT70_cartilage). The doses covering 50% to PTV70 calculated by AAA and PBC were 2.1%±1.0% and 3.7%±0.8% significantly higher than those using AXB, respectively (p

Introduction External beam radiation therapy (EBRT) with short-term androgen deprivation therapy is the standard of care for intermediate-risk prostate cancer patients. However, no study to date has evaluated the hormonal kinetics or sexual and hormonal function recovery after cessation of short-term luteinizing hormone (LH)-releasing hormone (LHRH) antagonist treatment. Patients and Methods Ten intermediate-risk prostate cancer patients (mean age, 69.9 years) were included. All patients received 4 months of LHRH antagonist (degarelix) treatment followed by EBRT. The testosterone, luteinizing hormone (LH), follicle-stimulating hormone, and prostate-specific antigen levels were measured and Expanded Prostate Cancer Index Composite questionnaires were completed before LHRH antagonist therapy at baseline; 1, 2, 3, and 4 months after the first injection of LHRH antagonist treatment; and every 2 months thereafter until 18 months. Results The testosterone levels were at the castration level at 1 month after the first LHRH antagonist injection. The median interval to recover a normal testosterone level (> 7.2 nmol/L) was 7 months after the last LHRH antagonist administration. The LH and follicle-stimulating hormone levels decreased but had increased more than twice above baseline at 15 months after the last LHRH antagonist injection. The sexual function and hormonal bother subdomain scores and sexual and hormonal domain scores decreased once after LHRH antagonist treatment but had significantly recovered thereafter ( P Conclusion In most patients, the testosterone level had normalized within 9 months after the last LHRH administration. Sexual and hormonal function recovered after short-term LHRH antagonist administration for neoadjuvant therapy before EBRT.

Intensity-modulated radiation therapy (IMRT) is a major therapeutic option for localized prostate cancer. Image-guided radiation therapy (IGRT) allows tumor visualization and corrects the errors caused by daily internal movement of the prostate. The current study retrospectively compared the acute toxicities and biochemical tumor control outcomes of prostate IMRT achieved using two IGRT techniques: bony structure-based IGRT (B-IGRT) and prostate-based IGRT (P-IGRT). Between February 2011 and July 2014, 96 patients with low- or intermediate-risk prostate cancer were treated using P-IGRT based on cone-beam computed tomography (CBCT; 76 Gy) without fiducial markers. This group of patients was compared with a similar cohort of 96 patients who were treated with B-IGRT (74 Gy) between July 2007 and September 2011. The planning target volume (PTV) margins were 1–3 mm smaller in the P-IGRT group than in the B-IGRT group. The median follow-up periods for all patients, the P-IGRT group, and the B-IGRT group were 42, 32, and 64 months, respectively. A significantly lower incidence of acute grade 2 or higher gastrointestinal toxicities was observed in the P-IGRT group compared with the B-IGRT group (3 vs. 11%; p = 0.049). The prostate-specific antigen failure-free survival rates at 3 years were 95.5 and 92.7% for the P-IGRT and B-IGRT groups, respectively (p = 0.534). IMRT with P-IGRT allows PTV margin reduction without sacrificing tumor control, which successfully reduces acute rectal toxicity compared with IMRT with B-IGRT.

Several studies have confirmed a dosimetric advantage associated with use of a smaller leaf in intensity-modulated radiation therapy (IMRT). However, no studies have identified any clinical benefits. We investigated the effect of a smaller multileaf collimator (MLC) width on the onset of late rectal bleeding after high-dose prostate IMRT. Two hundred and five prostate cancer patients were treated with a total dose of 78 Gy in 39 fractions by use of a dynamic MLC technique; however, two different MLC were used: a 10-mm-wide device and a 5-mm-wide device. Gastrointestinal toxicity and several clinical factors were assessed. The 5-year actuarial risk of grade 2 or higher rectal bleeding was 6.9 % for the 10-mm-wide group (n = 132) and 1.8 % for the 5-mm-wide group (n = 73) (p = 0.04). The median estimated rectal doses for the two groups were 55.1 and 50.6 Gy (p

Long-term outcomes of dose-escalated intensity-modulated radiation therapy (IMRT) combined with neoadjuvant (NA) androgen deprivation therapy (ADT) under an early salvage policy in patients with locally advanced prostate cancer (LAPC) were evaluated. Data from 120 patients with T3-T4N0M0 adenocarcinoma of the prostate treated with IMRT were analyzed. NA-ADT with a median duration of 6 months was provided in all cases. Seventy-eight Gy, at 2 Gy per fraction, was delivered to the prostate and seminal vesicles. Adjuvant ADT (A-ADT) was not provided for any patient following the completion of IMRT. Salvage ADT (S-ADT) commenced when PSA values >4 ng/ml. The median follow-up period was 97 months. S-ADT was initiated in 39 patients. The median PSA value at the initiation of S-ADT was 5.7 ng/ml. The 8-year biochemical relapse-free survival, prostate cancer-specific survival, overall survival and S-ADT-free rates were 53.2 % [95 % confidence interval (CI) 43.4, 62.1], 96.6 % (95 % CI 91.2, 98.7), 89.1 % (95 % CI 81.5, 93.7) and 66.6 % (95 % CI 60, 74.6), respectively. The estimated 8-year cumulative incidence rates of grade 2–3 late gastrointestinal, and grade 2–3 genitourinary toxicity were 7.6 and 10.7 %, respectively. No grade 4 toxicity was observed. High-dose IMRT, combined with NA-ADT for LAPC, was associated with favorable long-term disease-specific and overall survival outcomes, despite non-provision of A-ADT under the early S-ADT provision policy. This approach may represent a viable alternative to uniform provision of long-term A-ADT, because two-thirds of the patients maintained ADT-free status over an 8-year period after IMRT. Prospective trials will be required.

8 Background: The purpose of this trial was to prospectively evaluate the short-term outcomes of moderately hypofractionated intensity-modulated radiation therapy (MH-IMRT) for localized prostate cancer. Methods: In November 2013, we started a pilot study of MH-IMRT for prostate cancer. Eligible patients were 50 to 80 years old and had D’Amico’s low- or intermediate-risk disease. Fifty-four Gy in 15 fractions (3.6 Gy per fraction), in which the equivalent total dose in 2-Gy fractions to prostate cancer was estimated about 78 Gy, were delivered over 3 weeks using image-guided IMRT based on daily cone beam CT without intraprostatic fiducial markers. Neoadjuvant androgen deprivation therapy was given 4 to 8 months before the start of IMRT. The primary endpoint was incidence rates of acute toxicities, and the secondary endpoints were incidence rates of late toxicities at 2 years and biochemical relapse free survival (BRFS) at 2 years. Acute toxicities were evaluated based on the Common Terminology Criteria for Adverse Events version 4.0 criteria. Late toxicities were evaluated based on RTOG/EORTC Late Radiation Morbidity Scoring Schema. Biochemical relapse was defined according to the Phoenix definition (absolute nadir + 2 ng/ml). The planned sample size was 25 patients. Results: Twenty-five patients were enrolled in this trial. Twenty-four patients were treated with MH-IMRT, and 1 patient was treated with conventionally fractionated IMRT because his small intestine was close to the target. The median age in the cohort was 71 years old, and median follow-up period was 31 months (range 24-42). Four patients (17%) had low- and 20 (83%) had intermediate-risk disease. No grade ≥3 acute toxicity was observed and the incidence rates of grade 2 acute genitourinary and gastrointestinal toxicities were 21% and 4%, respectively. So far no grade ≥2 late toxicity has been observed and the 2-year BRFS is 95.8%. Transient PSA elevation over 0.4 ng/ml was observed in 11 patients (46%) and in 5 patients (21%) PSA rose ≥1.0 ng/ml above nadir. Conclusions: Sort-term outcome of MH-IMRT delivering 54 Gy in 15 fractions over 3 weeks for prostate cancer was comparable to that of conventionally fractionated IMRT. Clinical trial information: UMIN000012057.