Impact of prostate position-based image-guidance in intensity-modulated radiation therapy for localized prostate cancer.

BACKGROUND/PURPOSE: The long-term clinical impact of prostate position-based image-guided radiotherapy (IGRT) for localized prostate cancer remains unclear. MATERIALS AND METHODS: We retrospectively compared clinical outcomes following intensity-modulated radiation therapy (IMRT) with cone-beam computed tomography-based prostate position-based IGRT (P-IGRT) or without P-IGRT (non-P-IGRT). From June 2011, we applied P-IGRT in IMRT for intermediate-risk (IR) prostate cancer (PCa) (D'Amico risk classification) (76 Gy in 38 fractions, with smaller margins). Clinical outcomes of patients who received P-IGRT between June 2011 and June 2019 were retrospectively compared with those of patients with IR PCa who received IMRT without P-IGRT between October 2002 and May 2011 in our institution (74 Gy in 37 fractions). RESULTS: A total of 222 consecutive patients were analyzed: 114 in the P-IGRT cohort and 108 in the non-P-IGRT cohort. The median follow-up period after IMRT was 7.1 years for the P-IGRT cohort and 10.8 years for the non-P-IGRT cohort. The biochemical failure-free rate was significantly better in the P-IGRT cohort (94.9% for the P-IGRT cohort vs 82.7% for the non-P-IGRT cohort at 10 years, p = 0.041). The rate of rectal bleeding which needs intervention including the use of suppositories was significantly lower in the P-IGRT cohort (p < 0.001). CONCLUSIONS: The use of P-IGRT with higher doses and smaller margins was correlated with significantly better biochemical control, and a lower incidence of rectal bleeding in IMRT for intermediate-risk prostate cancer. The enhanced accuracy using P-IGRT has the potential to independently improve disease control and reduce late rectal bleeding.

A multi-institutional observational study on the effects of three-dimensional radiotherapy and weekly 40-mg/m2 cisplatin on postoperative uterine cervical cancer patients with high-risk prognostic factors.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Decreased acute toxicities of intensity-modulated radiation therapy for localized prostate cancer with prostate-based versus bone-based image guidance.

BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: IMRT with P-IGRT allows PTV margin reduction without sacrificing tumor control, which successfully reduces acute rectal toxicity compared with IMRT with B-IGRT.

Clinical effect of multileaf collimator width on the incidence of late rectal bleeding after high-dose intensity-modulated radiotherapy for localized prostate carcinoma.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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 < 0.001), respectively. Univariate analysis showed that acute toxicity, rectal V30-60, median rectal dose, normal tissue complication probability (NTCP), and MLC type were significant predictive factors for late rectal toxicity. In multivariate analysis, acute toxicity and NTCP remained significant. CONCLUSION: In our planning approach for prostate IMRT, a decrease in MLC width from 10 to 5 mm contributed to further rectal dose reduction, which was the most important predictor of late rectal toxicity.

Ten-year outcomes of intensity-modulated radiation therapy combined with neoadjuvant hormonal therapy for intermediate- and high-risk patients with T1c-T2N0M0 prostate cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Long-term outcomes of intensity-modulated radiation therapy combined with neoadjuvant androgen deprivation therapy under an early salvage policy for patients with T3-T4N0M0 prostate cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Dosimetric evaluation of the Acuros XB algorithm for a 4 MV photon beam in head and neck intensity-modulated radiation therapy.

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 (PTV70). 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 (PTV(70_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 < 0.01). The increases in doses to PTV(70_cartilage) calculated by AAA and PBC relative to AXB were 3.9% and 5.3% on average, respectively, and were relatively greater than those in the entire PTV70. AXB was found to be in better agreement with measurement in phantoms in heterogeneous areas for the 4 MV photon beam. Considering AXB as the standard, AAA and PBC overestimated the IMRT dose for head and neck cancer. The dosimetric differences should not be ignored, particularly with cartilaginous structures in PTV.

[Recent progress in radiation therapy].

Causing selective damage to tumors is an important issue in radiation therapy. This is usually addressed using either a biological or a physical approach. The former includes chemoradiotherapy and a combination of targeted drugs and radiation whereas the latter includes stereotactic radiotherapy, intensity-modulated radiotherapy and particle therapy. However, these sophisticated radiotherapy techniques are inadequate due to tumor movement and therefore 4-dimensional radiotherapy which addresses this problem is being clinically investigated.

Long-Term Outcomes of a Prospective Study on Highly Hypofractionated Intensity Modulated Radiation Therapy for Localized Prostate Cancer for 3 Weeks.

PURPOSE: Reports of radiation therapy for prostate cancer using dose fractions between moderate hypofractionation and ultrahypofractionation are limited. This pilot study involved the application of highly hypofractionated intensity modulated radiation therapy (IMRT) in 15 fractions for 3 weeks and the number of fractions was intermediate between the 2 previously mentioned dose fractions. The long-term outcomes are reported. METHODS AND MATERIALS: From April 2014 to September 2015, patients with low- to intermediate-risk prostate cancer received 54 Gy in 15 fractions (3.6 Gy per fraction) for 3 weeks using IMRT without intraprostatic fiducial markers or a rectal hydrogel spacer. Neoadjuvant hormone therapy (HT) was administered for 4 to 8 months. Adjuvant HT was not administered to any patients. Rates of biochemical relapse-free survival, clinical relapse-free survival, overall survival, and the cumulative incidence of late grade ≥2 toxicities were analyzed. RESULTS: Twenty-five patients were enrolled in this prospective study; 24 of them were treated with highly hypofractionated IMRT (17% had low-risk and 83% had intermediate-risk disease). The median neoadjuvant HT duration was 5.3 months. The median follow-up period was 77 months (range, 57-87 months). Biochemical relapse-free survival, clinical relapse-free survival, and overall survival rates were 91.7%, 95.8%, and 95.8% at 5 years, and 87.5%, 86.3%, and 95.8% at 7 years, respectively. Neither grade ≥2 late gastrointestinal toxicity nor grade ≥3 late genitourinary toxicity was observed. The cumulative incidence rates of grade 2 genitourinary toxicity were 8.5% and 18.3% at 5 and 7 years, respectively. CONCLUSIONS: Highly hypofractionated IMRT delivering 54 Gy in 15 fractions for 3 weeks for prostate cancer without intraprostatic fiducial markers facilitated favorable oncological outcomes without severe complications. This treatment approach may be a possible alternative to moderate hypofractionation, but further validation is needed.

Dynamic tumor-tracking stereotactic body radiotherapy with real-time monitoring of liver tumors using a gimbal-mounted linac: A multi-institutional phase II study.

Background and purpose: This prospective multicenter phase II study aimed to evaluate the safety and efficacy of dynamic tumor tracking (DTT) stereotactic body radiotherapy (SBRT) with real-time monitoring of liver tumors using a gimbal-mounted system. Materials and methods: Patients with < 4 primary or metastatic liver tumors with diameters ≤ 50 mm and expected to have a respiratory motion of ≥ 10 mm were eligible. The prescribed dose was 40 Gy in five fractions. The primary endpoint was local control (LC) at 2 years. The secondary endpoints were overall survival (OS), progression-free survival (PFS), treatment-related toxicity, and tracking accuracy. Results: Between September 2015 and March 2019, 48 patients (48 lesions) with a median age of 74 years were enrolled from four institutions. Of these, 39 were diagnosed with hepatocellular carcinoma and nine with metastatic liver cancer. The median tumor diameter was 17.5 mm. DTT-SBRT was successfully performed in all patients; the median treatment time was 28 min/fraction. The median follow-up period was 36.5 months. The 2-year LC, OS, and PFS rates were 98.0 %, 88.8 %, and 55.1 %, respectively. Disease progression was observed in 33 (68.8 %) patients. One patient (0.2 %) had local recurrence, 31 (64.6 %) developed new hepatic lesions outside the irradiation field, and nine (18.8 %) had distant metastases (including overlap). Grade 3 late adverse events were observed in seven patients (14.5 %). No grade 4 or 5 treatment-related toxicity was observed. The median tracking accuracy was 2.9 mm. Conclusion: Employing DTT-SBRT to treat liver tumors results in excellent LC with acceptable adverse-event incidence.

Clinical features and risk factors for interstitial lung disease spreading in low-dose irradiated areas after definitive radiotherapy with or without durvalumab consolidation therapy for patients with non-small cell lung cancer.

BACKGROUND: The current standard of care for patients with unresectable locally advanced non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) combined with durvalumab consolidation therapy. However, radiotherapy (RT) always carries the risk of radiation pneumonitis (RP), which can preclude durvalumab continuation. In particular, the spread of interstitial lung disease (ILD) in low-dose areas or extending beyond the RT field often makes it difficult to determine the safety of continuation or rechallenging of durvalumab. Thus, we retrospectively analyzed ILD/RP after definitive RT with and without durvalumab, with assessment of radiologic features and dose distribution in RT. METHODS: We retrospectively evaluated the clinical records, CT imaging, and radiotherapy planning data of 74 patients with NSCLC who underwent definitive RT at our institution between July 2016 and July 2020. We assessed the risk factors for recurrence within one year and occurrence of ILD/RP. RESULTS: Kaplan-Meier method showed that ≥ 7 cycles of durvalumab significantly improved 1-year progression free survival (PFS) (p < 0.001). Nineteen patients (26%) were diagnosed with ≥ Grade 2 and 7 (9.5%) with ≥ Grade 3 ILD/RP after completing RT. There was no significant correlation between durvalumab administration and ≥ Grade 2 ILD/RP. Twelve patients (16%) developed ILD/RP that spread outside the high-dose (> 40 Gy) area, of whom 8 (67%) had ≥ Grade 2 and 3 (25%) had Grade 3 symptoms. In unadjusted and multivariate Cox proportional-hazards models adjusted for V20 (proportion of the lung volume receiving ≥ 20 Gy), high HbA1c level was significantly correlated with ILD/RP pattern spreading outside the high-dose area (hazard ratio, 1.842; 95% confidence interval, 1.35-2.51). CONCLUSIONS: Durvalumab improved 1-year PFS without increasing the risk of ILD/RP. Diabetic factors were associated with ILD/RP distribution pattern spreading in the lower dose area or outside RT fields, with a high rate of symptoms. Further study of the clinical background of patients including diabetes is needed to safely increase the number of durvalumab doses after CRT.

Ten-year outcomes of whole-pelvic intensity-modulated radiation therapy for prostate cancer with regional lymph node metastasis.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Low-Dose Volumetric Modulated Arc Therapy for a Patient With Head and Neck Involvement of Mycosis Fungoides: A Case Report With a Review of Literature.

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma that slowly progresses over a period of years to decades. In some cases, lesions that spread to the scalp, neck, or facial skin can have a significant impact on cosmetic appearance and a patient's quality of life. Among the various treatments, radiation therapy is one of the most effective treatment modalities for patients with symptomatic cutaneous lesions. We report on an MF patient who had gradually increasing patches and plaques on the scalp, face, and neck and who underwent irradiation with 20 Gy administered in 10 fractions using volumetric modulated arc therapy. After undergoing this highly conformal technique, the patient obtained prolonged local control and significant alleviation of symptoms with acceptable adverse events. This technique constitutes a promising approach for treating a complex target due to its ability to provide homogeneous coverage of irregularly shaped target volumes along with its ability to preserve organs at risk. In addition, we systematically reviewed clinical reports on the management of extensive cutaneous lesions in MF patients undergoing other irradiation techniques.

Dynamic conformal arc radiotherapy with rectum hollow-out technique for localized prostate cancer.

PURPOSE: To report the feasibility of dynamic conformal arc radiotherapy with rectum hollow-out technique (DCAT-HO) for localized prostate cancer. METHODS AND MATERIALS: Between October 2000 and April 2007, 204 patients with clinically localized or locally advanced prostate cancer were treated with DCAT-HO. All patients were given neoadjuvant total androgen deprivation (AD) therapy (median 6 months, range 2-27 months). All patients with T3 or T4 stage received post-irradiation AD for 24 months. A total of 128 patients (63%) were treated with 70Gy, and 76 patients (37%) were treated with 74Gy. Acute and late toxicities were scored by the Radiation Therapy Oncology Group morbidity grading scales. PSA relapse was defined as three successive PSA elevations after a post-treatment nadir. The median follow-up was 37 months. RESULTS: Both the acute Grade 2 rectal and urinary toxicities were 1.0%, and no patients experienced acute Grade 3 or higher symptoms. The 3-year rates of both late Grade 2 rectal and urinary toxicities were 3.4%. The 3-year PSA relapse-free survival for low, intermediate, and high-risk group patients treated with 70 Gy were 54%, 75%, and 87%, respectively. CONCLUSIONS: These findings demonstrate the feasibility of DCAT-HO in a large number of patients with short follow-up. DCAT-HO reduced the volume of the rectum exposed to higher doses and this led to an overall reduction in late rectal toxicity.

Determination of the irradiation field for clinical T1-T3N0M0 thoracic/abdominal esophageal cancer based on the postoperative pathological results.

OBJECTIVE: In patients with thoracic/abdominal esophageal cancer with no clinical evidence of lymph node metastasis, there is no consensus about whether the irradiation field should include regional lymph nodes. In this study, the extent of the irradiation field for clinical stage T1-3N0M0 esophageal cancer was determined based on the postoperative pathological results. METHODS: From July 1989 to June 2008, 103 patients diagnosed with clinical stage T1-3N0M0 thoracic/abdominal esophageal cancer underwent standard esophagectomy and regional lymph node dissection at the Aichi Cancer Center Hospital. Of these 103 patients, the pathological results of the resected specimens could be confirmed in 95 (92%) patients. The pathological lymphatic spread was reviewed retrospectively, and the extent of the irradiation field was determined based on the postoperative pathological results. RESULTS: Of 95 patients with clinical stage T1-3N0M0 esophageal cancer, 40 (42.1%) had pathological lymph node metastases, and the frequency of nodal metastases was studied by tumor location. The rates of lymph node metastases for the upper, middle, lower and abdominal esophagus were 37.5%, 32.5%, 46% and 70%, respectively. CONCLUSIONS: Pathological lymph nodes metastases are often seen after operation in clinical stage T1-3N0M0 esophageal cancer. In the present study, the optimal lymph nodes to be included in the irradiation field were determined according to the primary site in the esophagus.

Chemoradiotherapy for locally recurrent nasopharyngeal carcinoma: treatment outcome and prognostic factors.

OBJECTIVE: To evaluate the treatment outcome of patients with locally recurrent nasopharyngeal carcinoma (NPC) treated with re-irradiation and chemotherapy. METHODS: Between 1991 and 2004, 36 patients with locally recurrent NPC received re-irradiation and chemotherapy. The median re-irradiation dose was 37.9 Gy; the median total dose of prior irradiation and re-irradiation was 104.4 Gy. The outcome is studied retrospectively and also evaluated the prognostic factors and toxicities. RESULTS: With a median follow-up of 40 months, 3-year overall survival (OS) was 58.3% and 3-year progression-free survival (PFS) was 25.0%. Patients aged <50 and of early stage at recurrence had a significantly better OS and PFS. Over Grade 3 of late toxicities were seen in patients received a total dose of >110 Gy. CONCLUSIONS: Age and stage at recurrence were identified as prognostic factors for OS and PFS. Patients received external beam radiation therapy at a total dose of more than 110 Gy should be careful for severe late toxicities, and it is thought to be the optimal dose for recurrent tumor.

A pilot study of highly hypofractionated intensity-modulated radiation therapy over 3 weeks for localized prostate cancer.

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.

Recovery of Serum Testosterone Levels and Sexual Function in Patients Treated With Short-term Luteinizing Hormone-releasing Hormone Antagonist as a Neoadjuvant Therapy Before External Radiotherapy for Intermediate-risk Prostate Cancer: Preliminary Prospective Study.

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 < .05). 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.

Correlation between urinary dose and delayed radiation cystitis after 78 Gy intensity-modulated radiotherapy for high-risk prostate cancer: A 10-year follow-up study of genitourinary toxicity in clinical practice.

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.