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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.

We analyzed the efficacy of definitive chemoradiotherapy (CRT) for patients with hypopharyngeal cancer (HPC). Subjects comprised 97 patients who were treated with definitive CRT from 1990 to 2006. Sixty-one patients (62.9%) with resectable disease who aimed to preserve the larynx received induction chemotherapy (ICT), whereas 36 patients (37.1%) with resectable disease who refused an operation or who had unresectable disease received primary alternating CRT or concurrent CRT (non-ICT). The median dose to the primary lesion was 66 Gy. The median follow-up time was 77 months. The 5-year rates of overall survival (OS), progression-free survival (PFS), local control (LC), and laryngeal preservation were 68.7%, 57.5%, 79.1%, and 70.3%, respectively. The T-stage was a significant prognostic factor in terms of OS, PFS and LC in both univariate and multivariate analyses. The 5-year rates of PFS were 45.4% for the ICT group and 81.9% for the non-ICT group. The difference between these groups was significant with univariate analysis (P = 0.006). Acute toxicity of Grade 3 to 4 was observed in 34 patients (35.1%). Grade 3 dysphagia occurred in 20 patients (20.6%). Twenty-nine (29.8%) of 44 patients with second primary cancer had esophageal cancer. Seventeen of 29 patients had manageable superficial esophageal cancer. The clinical efficacy of definitive CRT for HPC is thought to be promising in terms of not only organ preservation but also disease control. Second primary cancer may have a clinical impact on the outcome for HPC patients, and special care should be taken when screening at follow-up.

Background We planned a phase I study of weekly arterial infusion of docetaxel and cisplatin via a superficial temporal artery for recurrent head and neck cancer to determine the optimal dose. Methods The dose of cisplatin was fixed and the dose of docetaxel was escalated from 8 mg/m2, with an increase of 2 mg/m2 per step, to identify the maximum tolerated dose (MTD). In total, 4 courses of weekly chemotherapy were administered. Results Twelve patients were recruited to this trial. The MTD of docetaxel was 14 mg/m2. At this dose level, dose-limiting toxicity was observed in 2 of 3 patients. One patient experienced grade 3 leukopenia, while the other experienced grade 3 leukopenia. Myelosuppression was the dose-limiting toxicity for this regimen. Conclusion The recommended dose for weekly arterial infusion of docetaxel was identified as 12 mg/m2 combined with weekly cisplatin at 40 mg/m2, with 4 courses of each. © 2011 Wiley Periodicals, Inc. Head Neck, 2011

Purpose To evaluate the clinical effectiveness of pretreatment [(18)F] fluoro-2-deoxy-d-glucose-positron emission tomography for head-and-neck squamous cell carcinoma patients with nodal metastasis treated with chemoradiotherapy. Methods and Materials Between March 2002 and December 2006, 178 patients with head-and-neck squamous cell carcinoma and nodal metastasis underwent fluoro-2-deoxy-d-glucose positron emission tomography before chemoradiotherapy. Fluoro-2-deoxy-d-glucose uptake by both the primary lesion and the neck node was measured using the standard uptake value (SUV). The overall survival, disease-free survival, local control, nodal progression-free survival, and distant metastasis-free survival rates were calculated, and several prognostic factors were evaluated. Results The patients with a nodal SUV ≥6.00 had a significantly lower 3-year disease-free survival rate than those with a lower SUV (44% vs. 69%, p = .004). On multivariate analysis, a high SUV of nodal disease also proved to be a significantly unfavorable factor for disease-free survival ( p = .04, 95% confidence interval [CI], 1.02–3.23), nodal progression-free survival ( p = .05; 95% CI, 1.00–4.15), and distant metastasis-free survival ( p = .016; 95% CI, 1.25–8.92). Among the patients with a greater nodal SUV (≥6.00), those treated with planned neck dissection had better nodal progression-free survival than those in the observation group ( p = .04, hazard ratio, 2.36; 95% CI, 1.00–5.85). Conclusion Among head-and-neck squamous cell carcinoma patients treated with chemoradiotherapy, the pretreatment SUV of nodal disease was one of the strongest prognostic factors and also provided important information for the selection of patients suitable for planned neck dissection.

2009年2月～2010年1月までの間に超選択的動注化学療法と陽子線治療の併用療法を施行した進行舌癌13例を対象とした。年齢の中央値は63歳，男女比は男／女＝9/4，病理はすべて扁平上皮癌，病期はIII／IVA＝2/11，頸部リンパ節はN0/N1/N2b/N2c＝3/3/3/4であり，手術の場合，舌の全摘・亜全摘となる症例のみとした。治療の一次効果は13例中12例をcomplete response （CR），1例をpartial response（PR）と判定した。経過観察中にPRの1症例を加えた計4例に局所再発を認め，頸部リンパ節再発を計2例認めた。経過観察期間の中央値は12ヵ月と短いが，13例中8例は無病生存中であり，舌の局所制御率は69.2%（9/13）頸部リンパ節に関しては80.0%（8/10）であった。遠隔転移は1例もみられていない。再発症例の検討から，動注環流域確認の重要性が再確認された。経過観察期間は短いが，従来の放射線治療で問題とされてきた下顎骨・歯牙への晩期障害は認められておらず，晩期障害の軽減に有効である可能性が示唆された。また，通常の放射線治療では制御困難である頸部リンパ節の制御率向上の可能性が示唆された。

To review the treatment outcomes of limited-stage small-cell lung cancer (LS-SCLC) patients and to compare the outcomes among three groups in which the total radiation doses were 45 Gy with accelerated hyperfractionation (AHF),54 Gy with standard fractionation (SF), andor =54 Gy with SF.LS-SCLC patients that had been treated with chemoradiotherapy between 1997 and 2007 at Aichi Cancer Center Hospital were reviewed in this study. Of the 127 eligible patients, there were 37 patients in the AHF group, 29 in the SF54 Gy group, and 61 in the SFor =54 Gy group.Fifty-five patients (43%) were alive at the time of this analysis, and the median follow-up time of the surviving patients was 33 months. The median survival times were 30.0 months (95% confidence interval [CI] 16.3-43.7) for the AHF group, 14.0 months (CI 6.6-21.4) for the SF54 Gy group, and 41.0 months (CI 33.9-48.1) for the SFor = 54 Gy group. As for the local control rates, and the overall and progression-free survival rates, all outcomes were significantly lower in the SF54 Gy group than in the other two groups, although no significant difference was found between the AHF and SF/=54 Gy groups.These results suggest the importance of a high dose of radiation when using once-daily regimen. This study will support future prospective studies to establish optimal radiation doses and fractionation.

The purpose of this study was to compare radiation treatment plans (RTPs) that used intensity-modulated radiation therapy (IMRT) with helical tomotherapy (HT) or three-dimensional conformal radiation therapy (3D-CRT) for nasal natural killer/T-cell lymphoma (NNKTL). We created RTPs that used IMRT with HT or 3D-CRT for eight NNKTL patients previously treated at our institution and conducted a pilot comparison between the two modalities using the parameters of the target coverage and homogeneity for the planning target volume (PTV) and the maximum and mean doses for organs at risk (OARs). The clinical target volume (CTV) included the gross tumour volume with an additional margin of 1.5 cm and the nasopharynx, palates and nasal cavity; the PTV with the CTV plus a 2 mm margin received a total dose of 50 Gy. IMRT achieved significantly better PTV coverage, with more than 99% of the PTV receiving 90% and 95% of the prescribed dose, whereas 3D-CRT could not provide adequate coverage of the PTV, with 89.1+/-2.6% and 84.5+/-2.7% of the PTV receiving 90% and 95% of the prescribed dose, respectively (both p

Primarily combined radiotherapy and chemotherapy are used to treat unresectable non-small-cell lung cancer; however, the results are not satisfactory. In this study treatment results were retrospectively analyzed and the prognostic factors related to survival were identified. From March 1999 to January 2004, 102 patients with stage IIIA/IIIB non-small-cell lung cancer received definitive radiotherapy with or without chemotherapy. Radiotherapy involved a daily dose of 1.8-2.0 Gy five times a week; 60 Gy was set as the total dose. Maximal chemotherapy was given to patients with normal kidney, liver, and bone marrow functions. The 5-year overall survival rate was 22.2%; the median survival was 18 months. The median follow-up of surviving patients was 53 months. The complete or partial response rate was 85%. At the time of the last follow-up, 21 patients were alive and 81 patients had died, including 5 patients who had died due to radiation pneumonitis. There were significant differences in survival and in the fatal radiation pneumonitis rate between patients with superior lobe lesions and those with middle or inferior lobe lesions. Patients whose primary tumor is located in the superior lobe appear to have a better clinical outcome.

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.

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.

Distant metastasis was a major pattern of recurrence after postoperative radiotherapy (PORT) for squamous cell carcinoma (SCC) of the oropharynx, hypopharynx, and larynx. PORT provided good loco-regional control, with tolerable toxicities. Advanced pT and pN were unfavorable prognostic factors.To determine the clinical outcomes, and the patterns and risk factors for recurrence of SCCs of the oropharynx, hypopharynx, and larynx treated with surgery and PORT.We retrospectively reviewed 84 patients who received PORT after definitive surgery for SCC of the oropharynx, hypopharynx, or larynx between 2000 and 2010. The primary sites were the oropharynx in 25 patients, hypopharynx in 47 patients, and larynx in 12 patients.The 3-year overall survival (OS), progression-free survival (PFS), and loco-regional control (LRC) rates were 64.9%, 56.7%, and 92.1%, respectively. Recurrences were observed in 27 patients: 6 patients had loco-regional recurrence and 23 patients developed distant metastasis. On multivariate analysis, pT4 and pN2c-N3 displayed significantly worse effects on OS (p = 0.02 and p0.01, respectively) and PFS (p = 0.02 and p0.001, respectively). In the acute phase, 12 patients experienced grade 3 or 4 toxicities. There were no grade 5 toxicities. Late grade 3 toxicity developed in six patients and no grade 4 or 5 toxicities were observed.

The purpose of this study was to evaluate the feasibility and treatment plans of intensity-modulated radiation therapy using helical tomotherapy (HT) for brain metastases. Twenty-three patients with 1 to 4 brain metastases were treated with H T. In combination with whole-brain radiotherapy ( simultaneous plans), metastatic lesions, and the whole brain were treated with 50 Gy and 30 Gy, respectively, in 10 fractions, with a simultaneous integrated boost technique. In patients treated for brain metastases alone ( focal plans), metastatic lesions were treated with 35 or 37.5 Gy in 5 fractions. The treatment plans were compared regarding the conformation number (CN) and homogeneity index (HI), and differences in these indexes between simultaneous and focal plans were examined by Student's t-test. Seven and 16 patients were treated with simultaneous plans and focal plans, respectively. The mean ± SD of CN and HI values were 0.75 ± 0.13 and 0.063 ± 0.042, respectively, for simultaneous plans, and 0.73 ± 0.12 and 0.052 ± 0.023, respectively, for focal plans. The CN and HI between the two plans were not significantly different. Response rates in 13 patients with follow-up imaging were approximately 90% for both plans and the local control rate at 1 year was 69%. One patient with a huge tumor (34.0 cc) and WHO performance status 3 treated with focal plans experienced severe headache, requiring prolongation of the treatment time, and died at 8 days after completion of treatment. The exact cause of deterioration was uncertain as no radiological investigation was performed in this patient. No late complications were observed during follow-up periods up to 20 months. HT is a viable non-invasive technique for treatment of brain metastases and achieves high accuracy in terms of dose conformity and homogeneity.

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.

Purpose To evaluate the clinical efficacy of definitive radiotherapy for patients with superficial esophageal cancer. Material and methods From 1990 through 2006, 97 patients with stage I disease were treated with radiotherapy with or without chemotherapy. All patients were diagnosed with panesophagoscopy and computed tomography. Chemotherapy was added in 61 patients, and intra-cavitary brachytherapy (ICBT) was used in 27 patients. Results The patients were 90 men and seven women with a median age of 65.7years (range; 41–89). At last follow-up with a median follow-up duration of 35.7months, 3year-overall and progression-free survival (PFS) rates were 81.5% (95% C.I.=73.3–89.7%) and 55.8% (95% C.I.=45.2–66.4%), respectively. Shorter tumor length was a significantly favorable factor for the PFS rate ( P =0.02) and local failure-free (LFF) rate ( P =0.007) on both univariate and multivariate analyses. Although the addition of ICBT had no apparent benefit for survival or tumor control, the rate of severe adverse effects including lethal esophageal ulcers, showed a higher tendency in patients receiving ICBT. Conclusions Our results regarding efficacy from the viewpoint of organ preservation are promising. Special care would be taken for the use of ICBT for patients with superficial esophageal cancer, especially if they have received chemoradiotherapy.

Purpose To assess the feasibility of helical tomotherapy (HT) for patients with nasopharyngeal carcinoma. Methods and Materials From June 2006 to June 2007, 20 patients with nasopharyngeal carcinoma were treated with HT with ( n = 18) or without ( n = 2) systemic chemotherapy. The primary tumor and involved lymph node (PTV1) were prescribed 70 Gy and the prophylactic region 54 Gy at D95, respectively. The majority of patients received 2 Gy per fraction for PTV1 in 35 fractions. Parotid function was evaluated using quantitative scintigraphy at pretreatment, and posttreatment at 3 months and 1 year later. Results The median patient age was 53 years, ranging from 15 to 83. Our cohort included 5, 8, 4, 2, and 1 patients with disease Stages IIB, III, IVA, IVB, and IVC, respectively. Histopathological record revealed two for World Health Organization Type I and 18 for Type 2 or 3. The median duration time for treatment preparation was 9.5 days, and all plans were thought to be acceptable regarding dose constraints of both the planning target volume and organ at risk. All patients completed their treatment procedure of intensity-modulated radiation therapy (IMRT). All patients achieved clinical remission after IMRT. The majority of patients had Grade 3 or higher toxicity of skin, mucosa, and neutropenia. At the median follow-up of 10.9 months, two patients recurred, and one patient died from cardiac disease. Parotid gland function at 1 year after completion of IMRT was significantly improved compared with that at 3 months. Conclusion HT was clinically effective in terms of IMRT planning and utility for patients with nasopharyngeal cancer.

Purpose To assess the efficacy of alternating chemoradiotherapy combined with extended-field conformal radiotherapy for patients with high-risk cervical cancer. Methods and Materials Patients with previously untreated cervical cancer, with Stage III/IVA disease, or Stage IB/II with high-risk factor (primary tumor diameter ≥50 mm or positive lymph node) were entered into this study. Three cycles of chemotherapy with 3,500 mg/m 2 of 5-fluorouracil (5-FU) and nedaplatin (NDP) were accompanied with pelvic irradiation of 45.6–51.3 Gy in 24–27 fractions over 6 weeks. Prophylactic (36 Gy/20 fractions) or definitive (45–56 Gy) irradiation for para-aortic region was followed by pelvic irradiation. Results Between 1998 and 2004, 40 patients were recruited for this protocol study. Eighteen patients from Phase I setting were registered. Twenty-two patients were treated with NDP of 140 mg/m 2 (the recommended dose) in the Phase II segment. Twenty-five patients had T3 disease, and 25 patients had nodal disease including para-aortic involvement ( n = 5). Overall/progression-free survival rates at 5 years were 78.8 and 66.5%, respectively. The median follow-up time was 61.8 months (25.5–106.7). Hematologic and gastrointestinal Grade 3 or more toxicities were relatively high rate (27.5–45%); however, they were well manageable. Two for bladder toxicity of Grade 3 were noted. Comparing the data from historical control group evaluated by magnetic resonance imaging, alternating chemoradiotherapy revealed a significant favorable factor for survival and disease recurrence in multivariate analysis ( p Conclusion Acquired results from our unique protocol for cervical cancer with high-risk factor were thought to be promising, considering that the majority of our cohort consisted of high-risk population.

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.

Background: As AUA guideline for the Management of Clinically Localized Prostate Cancer: 2007 Update states “An assessment of the patient's life expectancy, overall health status, and tumor characteristics should be undertaken before any treatment decisions can be made," definitive therapy for localized prostate cancer is usually recommended for patients with 5-year life expectancy or more. In some cases, however, unexpected lethal disease is diagnosed and causes death within 5 years after prostate cancer treatment. It seems important to elucidate the characteristics of other causes of death during follow up period after definitive therapy for localized prostate cancer (PCa). Patients and Methods: We reviewed 664 consecutive patients who had received radical prostatectomy (RP, n = 107) or external beam radiotherapy (EBRT, n = 557) and been followed up over 5 years at our institute. Survival status was evaluated and cause of death was identified in dead cases. All cases underwent chest and abdominal computed tomography (CT) and bone scan that were negative for metastasis. Results: At latest follow up, 103 (15.5%) patients were dead of PCa (n = 48) and other causes (n = 55), respectively. Of the 55 patients who died of other causes, 26 did not survive 5 years after radical treatment for PCa. 54% of them died of other malignancies including lung (n = 7) and gastrointestinal (GI) tract (n = 3), lymphoma (n = 2), liver (n = 1), and pancreatic (n = 1) cancers. Non-cancer causes included cerebrovascular disease (n = 3), pulmonary disease (n = 3), ischemic heart disease (n = 2), and unknown (n = 3). Conclusions: Since all patients had negative chest CT for primary lung cancer, some patients with localized PCa seemed to have developed more lethal and rapid malignancy after treatment for PCa. Urologists may need to pay their attention that their patients undergo regular mass screening for common diseases even if they were under urological follow up. Pretreatment test for fecal occult blood may be useful to screen GI tract cancer before treatment initiation. Citation Format: Takashi Kobayashi, Tomomi Kamba, Naoki Terada, Toshinari Yamasaki, Itaru Ikeda, Haruo Inokuchi, Yoshiki Norihisa, Takashi Mizowaki, Takahiro Inoue, Kazutoshi Okubo, Koji Yoshimura, Masahiro Hiraoka, Osamu Ogawa. Non-prostate cancer death within 5 years after radical therapy in men with localized prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4677. doi:10.1158/1538-7445.AM2013-4677