High-dose Intensity-modulated Radiotherapy Research Articles

A Prospective Phase II Dose Escalation Study Using IMRT for High Risk N0M0 Prostate Cancer.

Published data supports the use of very high dose intensity modulated radiotherapy (IMRT) in achieving high efficacy and low toxicity for high-risk prostate cancer (HRPCa). This phase II multi-institutional non-randomized prospective dose escalation study using intensity modulated radiotherapy (IMRT) for high risk N0M0 prostate cancer was designed to investigate dose escalation using 1.8 Gy increments from baseline 75.6 Gy up to maximum 81 Gy, once dose volume constraints were adhered to. Inclusion criteria were patients undergoing a radical course of RT for high and very high-risk disease, defined as one or more of the criteria ≥ T3*, ≥ Gleason 8, Prostate specific antigen (PSA) > 20ng/ml. All patients received Androgen Deprivation Therapy (ADT) and none had radiological evidence of distant metastatic disease. The primary objective was to determine if dose escalated IMRT for high risk localized prostate cancer could provide freedom from biochemical relapse (BR; PSA rising > nadir +2ng/mL or initiation of salvage hormone therapy) similar to that reported in the literature. The Kaplan-Meier method was used to estimate survival times. Secondary objectives included OS, Disease Free Survival (DFS), and the incidence and severity of Genito-urinary (GU), Gastro-intestinal (GI) and erectile dysfunction (ED) toxicities (CTCAE v.3). Toxicities and performance status were collected and graded weekly during RT, 2 months after completing RT, 8 months' post RT, and 6 monthly thereafter to year five and annually thereafter to year nine. A total of 230 evaluable patients were enrolled between April 2009 and June 2016. The median follow-up was 7.3 years. The cumulative proportion of patients surviving without BR at 5 years was 91% (95% Confidence Interval (CI): 86% to 94%). Overall survival at 5 and 7 years was 92% (88% to 95%) and 89% (83% to 92%) respectively, while the cumulative proportion of patients free from disease was 89% (84% to 93%) at 5 years and 81% (75% to 86%) at 7 years. The incidence of acute G2 and G3 toxicities were; GU; 57.8% G2, 12.6% G3, GI; 15.2% G2, 0.4% G3, ED; 30.0% G2 and 61.7% G3. The incidence of late G2, G3 and G4 toxicities were; GU; 40.9% G2, 8.7% G3, GI; 36.5% G2, 2.2% G3, 0.4% G4, ED; 11.7% G2 and 86.1% G3. The percentage of patients receiving each dose level was; 3.5% received 75.6Gy in 42 fractions, 2.2% received 77.4Gy in 43 fractions, 93% received 81Gy in 45 fractions. The findings indicate that high-dose IMRT is well tolerated and is associated with excellent long-term tumor-control outcomes in patients with localized high and very high-risk prostate cancer, with 91% of patients surviving at 5 years without biochemical relapse. The rates of long term G3 GU and GI toxicity were low at 8.7% and 0.4% respectively.

High-dose (60 Gy) intensity-modulated radiotherapy with concurrent weekly cisplatin followed by intracavitary radiation in locally advanced cervical cancer: A phase II prospective clinical trial

ObjectiveRadiotherapy dose-escalation using intensity-modulated radiotherapy (IMRT) has been necessary to improve treatment results in cervical cancer. MethodsThis was a phase II prospective clinical trial. 88 patients with FIGO II-IVa cervical cancer were enrolled in a single center. They received high-dose (60 Gy) IMRT with weekly cisplatin to the primary tumor and clinically positive nodes followed by intracavitary radiation. The primary endpoint was 30-month PFS rate (Target; 82%, an increase of 20% compared to GOG 120 trial using standard-dose radiotherapy). Secondary endpoints were tumor response, toxicity, recurrence, distant metastasis, and overall survival. ResultsProgression-free survival rate at 30 months was 82.8%. Overall survival, locoregional recurrence, distant metastasis, and para-aortic recurrence rates at 30 months were 93.6%, 8.2%, 9.2%, and 2.4%, respectively. Forty-five (51.1%) of 88 patients achieved downstaging on MRI during radiotherapy and 80 (90.9%) patients had clinically complete response at three months after high-dose IMRT and intracavitary radiotherapy. The 30-month recurrence-free survival (92.9% vs. 73.1%, P = 0.009) and overall survival (100% vs. 87.0%, P = 0.006) were significantly higher in the downstaged group than in the non-downstaged group during radiotherapy. Grade 3 or higher hematologic toxicity was found in 11 (12.5%) patients and grade 3 or higher non-hematologic toxicity was found in 3 (3.4%) patients. Fourteen had chronic urinary (8.0%), intestinal (5.7%) toxicity, pelvic insufficiency fracture (2.3%) or vesicovaginal fistula (2.3%). ConclusionHigh-dose (60 Gy) IMRT with concurrent weekly cisplatin in locally advanced cervical cancer yielded favorable progression-free survival outcome. Tumor response during radiotherapy can be a significant prognostic factor for PFS.Clinical trial information: This prospective trial is registered at ClinicalTrials.gov Identifier: NCT02993653.

Impact of Long-term Adjuvant Hormonal Therapy in High-dose IMRT for Unfavorable Locally Advanced Prostate Cancer.

The aim of this study was to evaluate the benefit of adding long-term adjuvant hormonal therapy to high-dose intensity-modulated radiation therapy for locally advanced prostate cancer patients with multiple unfavorable risks. All cT3-4N0M0 prostate cancer patients with Gleason score 8-10 and prostate-specific antigen ≥30 ng/ml who received intensity-modulated radiation therapy to the prostate and seminal vesicle alone (78 Gy in 39 fractions) between September 2000 and June 2017 at our institution were analyzed retrospectively. All patients received short-term neoadjuvant hormonal therapy. Before May 2011, salvage hormonal therapy was initiated when prostate-specific antigen levels exceeded 4.0 ng/ml (early salvage hormonal therapy cohort). In June 2011, 2-year adjuvant hormonal therapy was added (adjuvant hormonal therapy cohort). Clinical outcomes were retrospectively compared using the log-rank test. In total, 88 patients (44 in both cohorts) were analyzed. Median follow-up periods were 10.9 and 6.1 years in early salvage hormonal therapy and adjuvant hormonal therapy cohorts, respectively. No significant difference in overall survival rates was observed (p=0.58). Disease controls were significantly better in the adjuvant hormonal therapy cohort: 95.5 versus 73.6% for castration-resistant prostate cancer-free rate (p=0.04), and 73.6 versus 34.1% for biochemical failure-free rate (p<0.001), both at 8 years, respectively. Among locally advanced prostate cancer patients with multiple unfavorable risks, adding long-term adjuvant hormonal therapy to high-dose intensity-modulated radiation therapy resulted in significantly better disease control than short-term hormonal therapy, even when salvaged early after biochemical failure.

High dose (54 Gy) pre-operative helical tomotherapy for retroperitoneal liposarcoma: Results of a phase II multicenter study

PurposeTo evaluate efficacy and feasibility of high-dose intensity-modulated radiotherapy (RT) with pre-operative helical tomotherapy, delivering 54 Gy/30 fractions in patients with retroperitoneal liposarcomas (RPLS). Materials and MethodsPatients with operable, biopsy-proven, RPLS were included in this phase II multicenter study (ClinicalTrials.gov: NCT01841047). The primary objectives were to analyze loco-regional relapse free survival (LRFS), overall survival (OS) and toxicities, graded according to CTCAE V3.0. ResultsFrom April 2009 to September 2013, 48 patients were included. Histological types were: 20 well differentiated and 28 dedifferentiated liposarcomas. Median clinical target volume (CTV) was 2570 cc (range, 230–8734 cc). The radio-surgical schedule was completed as planned in all patients apart from one. A monobloc wide excision was achieved for all patients. Surgical margins were R0 (16; 34%), R1 (28; 60%), R2 (2; 4%) or missing (1, 2%).With a median follow-up of 5.5 years, 3-year LRFS rate was 74.2% (95%CI: [59.1%; 84.5%]). At 5 years, cumulative incidence of loco-regional relapse for well differentiated and dedifferentiated RPLS was 10% and 18%, respectively. The 5-year OS was 73.9% [95%CI: 58.7–84.3%]. During RT, the most common grade 3–4 adverse events were hematological (N = 20; 41.6%). After surgery and during follow-up, 17 patients (35.4%) presented a grade 3–4 toxicity. Two patients (4.1%) died due to a duodenal toxicity. Nine second cancers were observed. ConclusionFrom this phase II trial of preoperative RT in RPLS patients, the dose level proposed cannot be considered safe, leading to non-negligible toxicity and second cancers rates. Our results, combined with STRASS-1 study, suggest that the ideal indication of RT for patients with RPLS still remains to be determined.

High-dose planned adaptive helical tomotherapy for cutaneous angiosarcoma of the scalp.

The purpose of this study was to investigate the feasibility and effectiveness of high-dose planned adaptive intensity-modulated radiation therapy (IMRT) with helical tomotherapy (HT) for cutaneous angiosarcoma (cAS) of the scalp. This retrospective cross-sectional included atotal of 12consecutive patients with cAS of the scalp who underwent high-dose planned adaptive IMRT with HT. Prescribed doses were 72.5-74 Gy in 35-37 fractions for the gross tumor volume plus a1-2 mm margin (PTV1), 58-60 Gy in 29-30 fractions for the clinical target volume plus a2-3 mm margin (PTV2), and 46 Gy in 23fractions for the clinical target volume plus a5-15 mm margin (PTV3) over periods of 7.5, 6and 4.5weeks, respectively. The estimated 1‑year and 2‑year overall survival rate were 65.6% and 27.3%, respectively, and the local progression-free survival at 2years was 74.1%. All local recurrences were either in or marginal to the PTV2 or PTV3. No local recurrence was observed in the PTV1. All patients tolerated the treatment without grade3 or higher adverse events during the radiotherapy period. No late adverse events were observed during the follow-up period. Planned adaptive high-dose IMRT with HT has the potential to improve local control rate without increasing adverse events.

Extended follow-up of a phase 2 trial of xevinapant plus chemoradiotherapy in high-risk locally advanced squamous cell carcinoma of the head and neck: a randomised clinical trial

IntroductionWe report long-term efficacy and overall survival (OS) results from a randomised, double-blind, phase 2 study (NCT02022098) investigating xevinapant plus standard-of-care chemoradiotherapy (CRT) vs. placebo plus CRT in 96 patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). MethodsPatients were randomised 1:1 to xevinapant 200 mg/day (days 1–14 of a 21-day cycle for 3 cycles), or matched placebo, plus CRT (cisplatin 100 mg/m2 every 3 weeks for 3 cycles plus conventional fractionated high-dose intensity-modulated radiotherapy [70 Gy/35 F, 2 Gy/F, 5 days/week for 7 weeks]). Locoregional control, progression-free survival, and duration of response after 3 years, long-term safety, and 5-year OS were assessed. ResultsThe risk of locoregional failure was reduced by 54% for xevinapant plus CRT vs. placebo plus CRT but did not reach statistical significance (adjusted hazard ratio [HR] 0.46; 95% CI, 0.19–1.13; P = .0893). The risk of death or disease progression was reduced by 67% for xevinapant plus CRT (adjusted HR 0.33; 95% CI, 0.17–0.67; P = .0019). The risk of death was approximately halved in the xevinapant arm compared with placebo (adjusted HR 0.47; 95% CI, 0.27–0.84; P = .0101). OS was prolonged with xevinapant plus CRT vs. placebo plus CRT; median OS not reached (95% CI, 40.3-not evaluable) vs. 36.1 months (95% CI, 21.8–46.7). Incidence of late-onset grade ≥3 toxicities was similar across arms. ConclusionsIn this randomised phase 2 study of 96 patients, xevinapant plus CRT demonstrated superior efficacy benefits, including markedly improved 5-year survival in patients with unresected LA SCCHN.

High-Dose Versus Standard-Dose Intensity-Modulated Radiotherapy With Concurrent Paclitaxel Plus Carboplatin for Patients With Thoracic Esophageal Squamous Cell Carcinoma: A Randomized, Multicenter, Open-Label, Phase 3 Superiority Trial

The standard dose (SD) of definitive concurrent chemoradiotherapy (dCRT) remains 50.4 Gy in patients with esophageal cancer; a higher dose, when applied with conventional radiation therapy techniques, increases toxicities without improving survival. We investigated whether a high dose of 59.4 Gy using intensity-modulated radiation therapy (IMRT) would improve survival without increasing toxicities. Patients with inoperable thoracic esophageal squamous cell carcinoma (SCC) referred for dCRT were randomly assigned (1:1) to high-dose (HD) IMRT (59.4 Gy) or SD IMRT (50.4 Gy). Chemotherapy consisted of 6 cycles of concurrent weekly paclitaxel and carboplatin and a maximum of 2 cycles of consolidation chemotherapy. Nutritional intervention was implemented for patients with malnutrition on the basis of nutritional screening. The primary endpoint was median overall survival (mOS). Analyses were by modified intention to treat. Between April 30, 2016, and April 30, 2019, 167 patients were enrolled at 9 participating centers in China. Seventy-one patients in the HD and 73 patients in the SD groups were included in the analysis; 86.8% of the patients completed radiation therapy and 70.1% received 5 or 6 cycles of concurrent chemotherapy. The median follow-up was 36.0 months. The mOS was 28.1 and 26.0 months in the HD and SD arms, respectively (P=.54). A total of 7 treatment-related deaths were observed. Grade 3 or worse treatment-related toxicities were observed in 62% and 68.5% of the patients in the HD and SD arms, respectively (P=.675). For patients with inoperable thoracic esophageal SCC, a dose of 59.4 Gy did not improve survival compared with the SD of dCRT using IMRT.

Prevalence of Neurocognitive Impairment for NPC Survivors after Definitive Intensity-Modulated Radiotherapy: A Cross-Sectional Study

<h3>Purpose/Objective(s)</h3> High-dose intensity-modulated radiotherapy (IMRT) has led to excellent prognosis in patients with localized nasopharyngeal carcinoma (NPC). Given the relatively young age of onset and the close anatomic relationship between the nasopharynx and the central nervous system, post-radiation neurocognitive impairment among long-term survivors represents an under-recognized late complication. This study aims to determine the prevalence and the affected cognitive domains in post-IMRT NPC survivors. <h3>Materials/Methods</h3> We undertook a cross-sectional study in a high-volume tertiary oncology center in Hong Kong. NPC survivors who underwent IMRT with a minimal post-radiotherapy interval of 1 year were eligible. All patients underwent an initial screening using the Montreal Cognitive Assessment-Hong Kong (MoCA-HK) test, followed by a 2-hour comprehensive battery of neurocognitive assessments covering 8 distinct domains: intellectual capacity (WAIS-IV), attention span (WAIS-IV digit span, WMS-III Visual Spatial Span), visual memory (WMS-III Visual reproduction span), verbal memory (Auditory Verbal Learning Test), processing speed (Color Trail Test), executive function (Stroop Test), motor dexterity (Grooved Pegboard Test) and language ability (Verbal Fluency Test). Mean percentiles and Z-scores of all neurocognitive assessments were compared with age- and/or education-matched population normative data using one-sample t-tests. Correlation of cognitive outcomes with clinical factors were analyzed using multivariable linear regression. <h3>Results</h3> A total of 182 NPC survivors were enrolled. The median post-radiotherapy interval was 6.9 years, 129 (70.9%) were long-term survivors at least 5 years beyond radiotherapy. The median age was 56 years old, 89% of the enrolled patients had stage III-IVA NPC by AJCC/UICC 8^th Edition, and 87% of patients received chemotherapy. The mean MoCA score was 23.6, 25.8% of patients were considered cognitively impaired. NPC survivors demonstrated significant cognitive impairment in verbal memory (p<0.001), processing speed (p<0.001), executive function (p<0.001), motor dexterity (p<0.001) and language ability (p=0.001). Most significant impairment was observed in executive function, mean z-scores of which were -1.76 to -1.38 below normative data. Post-IMRT interval, disease stage and chemotherapy usage showed no significant association with the degree of neurocognitive impairment. <h3>Conclusion</h3> Post-IMRT neurocognitive impairment was prevalent in NPC survivors. Neurocognitive function was not impaired globally but occurred predominantly in selected domains, particularly executive function. Cognitive assessment and training should be considered a part of survivorship care for NPC patients. Future research on the correlation between neurocognitive function and radiation dosimetry of various brain subsites would be informative.

Acute, Subchronic, and Chronic Complications of Radical Prostatectomy Versus Radiotherapy With Hormone Therapy in Older Adults With High-Risk Prostate Adenocarcinoma.

PurposeTo compare acute, subchronic, and chronic complications between older patients with high-risk localized prostate cancer (HR-LPC) receiving radical prostatectomy (RP) and high-dose intensity-modulated radiotherapy (IMRT) combined with long-term hormone therapy (HT).Patients and MethodsWe recruited older patients (≥80 years) with HR-LPC from the Taiwan Cancer Registry database. After propensity score matching, logistic regression analysis was used to compare the acute, subchronic, and chronic complication rates between patients who underwent RP (the RP group) and high-dose IMRT combined with long-term HT (the IMRT+HT group).ResultsBenign prostatic hyperplasia (BPH) symptoms and urinary incontinence (UI) were the most common complications over 5 years (BPH symptoms: RP, 17.69%; IMRT+HT, 29.58%; UI: RP, 10.47%; IMRT+HT, 5.50%). Compared with the RP group, the IMRT+HT group had higher odds of BPH symptoms and lower odds of UI and hernia after the 5-year follow-up period. The impotence rates were significantly higher in the IMRT+HT group than in the RP group at 3 months and 1 year after treatment and became nonsignificant after 2 years. At 5 years after treatment, the IMRT+HT group had lower risks of UI (adjusted odds ratio [aOR], 0.50; 95% confidence interval [CI], 0.28–0.88) and hernia (aOR, 0.21; 95% CI, 0.11–0.82) and a higher risk of BPH symptoms (aOR, 4.15; 95% CI, 2.82–7.37) than the RP group.ConclusionIMRT+HT was associated with lower UI and hernia risks than RP. By contrast, RP was associated with fewer complications of BPH over the follow-up period and less impotence during the first year after treatment. Our findings provide important and valuable references for shared decision-making for optimal therapy selection among older men with HR-LPC.

Long-Term Outcomes of a Phase I Trial of Weekly Docetaxel, Total Androgen Blockade, and Image Guided Intensity Modulated Radiation Therapy for Localized High-Risk Prostate Adenocarcinoma

PurposeOur purpose was to describe the long-term outcomes seen with the addition of concurrent weekly docetaxel to high-dose intensity modulated radiation (IMRT) to the prostate and androgen deprivation therapy in patients with high-risk nonmetastatic adenocarcinoma of the prostate. Methods and MaterialsNineteen patients with high-risk, localized prostate cancer were treated in a phase I trial with concurrent docetaxel at doses of 10 to 30 mg/m2, in a dose-escalated scheme, in addition to IMRT (77.4 Gy/43 fx) and neoadjuvant and concurrent combined androgen blockade (gonadotropin-releasing hormone agonist and antiandrogen). A gonadotropin-releasing hormone agonist was continued for an additional 24 months post radiation. Kaplan-Meier analysis was used to estimate the survival probabilities. ResultsAt a median follow-up of 10.5 years, 5-year and 10-year overall survival were found to be 89.5% and 68.4%, respectively. The median metastasis-free survival and progression-free survival were determined to be 11.3 years and 9.0 years, respectively. ConclusionsThis regimen produced a 10-year overall survival of 68% with a 10-year metastasis-free survival of 58%. Grade >2 toxicity was minimal. These limited data suggest that the addition of concurrent weekly docetaxel to high-dose IMRT for high-risk prostate cancer warrants further investigation.

Postoperative Intensity-Modulated Radiation Therapy for Myoepithelial Carcinoma in the Parotid Gland

Myoepithelial carcinoma (MC) is an extremely rare form of tumor, with no standard treatment established to date. Although several reports have discussed postoperative radiation therapy (PORT), few have applied intensity-modulated radiation therapy (IMRT), and none has described the dose and radiation field in detail. In this report, we describe a case of MC of the parotid gland that was treated with high-dose IMRT (70 Gy) after partial resection. The patient, a 61-year-old female, underwent excisional surgery and was diagnosed with MC arising from a pleomorphic adenoma (PA). Postoperative irradiation was administered as 70 Gy in 35 fractions of local radiation. The patient had cancer recurrence in the irradiated field. However, no serious adverse events associated with the radiation therapy have been confirmed, implying that postoperative high-dose radiation therapy may be safely administered via IMRT.

Intensity Modulated Radiation Therapy and Concurrent Chemotherapy for Locally Advanced Cervical Cancer Not Amenable to Brachytherapy

<h3>Hypothesis</h3> Cervical cancer patients ineligible for brachytherapy due to tumor geometry suffer poor local control and survival outcomes despite treatment with concurrent IMRT and chemotherapy. <h3>Purpose/Objective(s)</h3> In this study of patients with cervical cancer tumors too large for brachytherapy boost, we report tumor control and toxicity outcomes of patients treated with intensity modulated radiation therapy (IMRT) and concurrent chemotherapy. <h3>Materials/Methods</h3> We performed a retrospective study of patients with FIGO 2018 stage III-IVB cervical cancer treated with high dose IMRT and concurrent cisplatin without brachytherapy at a tertiary academic center from 2005 – 2020. All patients underwent FDG-PET/CT and were examined by an experienced gynecologic brachytherapist. Patients received 48.6-50.4 Gy in 25 to 35 fractions to the cervix, pelvis, and if involved on FDG-PET, paraaortic, and supraclavicular lymph nodes with IMRT. Lymph nodes greater than 3 cm received a simultaneous boost to a total dose of 60 Gy. The primary metabolically active cervical tumor received a simultaneous or sequential boost without additional planning margin to a total dose of 60-70.2 Gy with concurrent weekly cisplatin or carboplatin. Toxicity is reported with CTCAEv5. <h3>Results</h3> Twenty patients out of 1005 (2%) were identified with median age of 55 (range 37 – 76) years. Sixty percent were Caucasian, 35% black, 5% Asian. Median metabolic primary tumor volume was 111 cm3 (range 26 – 473). Nineteen (95%) had squamous histology and one (5%) had adenosquamous. Median follow up was 15 months (range 2 - 154). 7 (35%) patients had PET positive pelvic lymph nodes, 5 (25%) paraaortic, and 3 (15%) supraclavicular. Classic FIGO stage was: III 7 (35%), IVA 11 (55%), IVB 2 (10%). FIGO 2018 stage was: III 3 (15%), IVA 9 (45%), IVB 8 (40%). Five (20%) patients were disease free at the end of follow up (III 1 (33%), IVA 3 (33%), IVB 1 (13%)). One- and 2-year freedom from local progression were 70% and 60%, respectively. One and 2-year OS were 60% and 35%, respectively. Grade 3 anemia and nausea occurred in 4 (20%), and 2 (10%) patients, respectively. Grade 4 diarrhea and nausea occurred in 1 (5%) and 3 (15%) patients, respectively. Two (10%) patients died of treatment-related toxicity. <h3>Conclusion</h3> Our study shows that patients ineligible for brachytherapy suffer poor local control and survival outcomes. Grade 4-5 toxicity occurred in 25% of patients. Novel radiation techniques for this patient population should be further explored.

OLIGOPELVIS GETUG P07, a Multicenter Phase II Trial of Combined High-dose Salvage Radiotherapy and Hormone Therapy in Oligorecurrent Pelvic Node Relapses in Prostate Cancer

BackgroundOligorecurrent pelvic nodal relapse in prostatic cancer is a challenge for regional salvage treatments. Androgen depriving therapies (ADTs) are a mainstay in metastatic prostate cancer, and salvage pelvic radiotherapy may offer long ADT-free intervals for patients harboring regional nodal relapses. ObjectiveTo assess the efficacy of the combination of ADT and salvage radiotherapy in men with oligorecurrent pelvic node relapses of prostate cancer. Design, setting, and participantsWe performed an open-label, phase II trial of combined high-dose intensity-modulated radiotherapy and ADT (6 mo) in oligorecurrent (five or fewer) pelvic node relapses in prostate cancer, detected by fluorocholine positron-emission tomography computed tomography imaging. Outcome measurements and statistical analysisThe primary endpoint was 2-yr progression-free survival defined as two consecutive prostate-specific antigen levels above the level at inclusion and/or clinical evidence of progression as per RECIST 1.1 and/or death from any cause. Results and limitationsBetween August 2014 and July 2016, 67 patients were recruited in 15 centers. Half of the patients had received prior prostatic irradiation. The median age was 67.7 yr. After a median follow-up of 49.4 mo, 2- and 3-yr progression-free survival rates were 81% and 58%, respectively. Median progression-free survival was 45.3 mo. The median biochemical relapse–free survival (BRFS) was 25.9 mo. At 2 and 3 yr, the BRFS rates were 58% and 46%, respectively. Grade 2 + 2-yr genitourinary and gastrointestinal toxicities were 10% and 2%, respectively. ConclusionsCombined high-dose salvage pelvic radiotherapy and ADT appeared to prolong tumor control in oligorecurrent pelvic node relapses in prostate cancer with limited toxicity. After 3 yr, nearly half of patients were in complete remission. Our study showed initial evidence of benefit, but a randomized trial is required to confirm this result. Patient summaryIn this report, we looked at the outcomes of combined high-dose salvage pelvic radiotherapy and 6-mo-long hormone therapy in oligorecurrent pelvic nodal relapse in prostatic cancer. We found that 46% of patients presenting with oligorecurrent pelvic node relapses in prostate cancer were in complete remission after 3 yr following combined treatment at the cost of limited toxicity.

Patient reported toxicity and quality of life after hypofractionated high-dose intensity-modulated radiotherapy for intermediate- and high risk prostate cancer

Background and purposeFor irradiation of localized prostate-cancer, moderately-hypofractionated regimens with a variety of dose per fraction are used. We adopted a regimen of 70 Gy in 28 fractions of 2.5 Gy, using state of the art radiotherapy (RT) and closely monitored the efficacy, toxicity and health-related quality of life (HRQoL) in a large cohort, using patient-reported outcomes. Materials and methodsBetween 2008 and 2016, 462 patients with intermediate- to high-risk localized prostate cancer were treated with RT, 28 fractions of 2.5 Gy, using IMRT/VMAT, an online fiducial-maker based correction protocol and a daily inserted endorectal balloon. Overall freedom from failure (no biochemical or clinical recurrence) , as well as self-reported genitourinary (GU) and gastrointestinal (GI) related toxicity and HRQoL are reported. ResultsOverall freedom from failure rates at 3 and 5 years were 92.0% (89.1–94.9%) and 83.5% (78.6–88.4%), respectively. Prevalence rates of grade ≥ 2 GU/GI-toxicity were 16.3%/6.3% and 22,1%/3.2% after 3 and 5 years respectively. The 5-year actuarial incidences of grade ≥ 2 GU/GI-toxicity were 43.5%/18.5%. HRQoL worsened during RT and gradually recovered thereafter, In accordance with the prevalence rates. ConclusionTreatment of intermediate- or high-risk localized prostate cancer with RT to 70 Gy in 28 fractions with IMRT/VMAT, using fiducial markers and an endorectal balloon leads to good long-term tumor control rates and acceptable patient reported toxicity rates. Furthermore, patient-reported outcomes, including HRQoL, are essential for a good comparison between different studies. Finally, prevalence rates show a better correlation with HRQoL than actuarial incidence rates do and might therefore better represent the burden of toxicity.

PRSOR07 Presentation Time: 12:30 PM: Does the Sequence of High-Dose Rate Brachytherapy Boost and IMRT for Prostate Cancer Impact Early Disease and Toxicity Outcomes? Results from a Single Institution Analysis

Purpose: Optimal sequencing of high-dose rate (HDR) brachytherapy (BT) boost and whole pelvis intensity-modulated radiotherapy (IMRT) for definitive treatment of prostate cancer (PCa) is not defined. The prospective Timing of HDR brachytherapy with EBRT in Prostate Cancer (THEPCA) trial is ongoing to address this question. To our knowledge, we present the first report comparing early toxicity and disease outcomes for PCa patients treated with HDR-BT upfront vs. IMRT upfront combined with androgen deprivation therapy (ADT).

Oncologic Outcomes of Radical Prostatectomy and High-Dose Intensity-Modulated Radiotherapy with Androgen-Deprivation Therapy for Relatively Young Patients with Unfavorable Intermediate-Risk Prostate Adenocarcinoma.

Simple SummaryScarce reports have evaluated oncologic outcomes in relatively young men with unfavorable intermediate-risk prostate cancer (UIR-PC) receiving radical prostatectomy (RP) or high-dose intensity-modulated radiotherapy (IMRT). After a literature review, we present the leading and largest head-to-head propensity score-matched study to examine all-cause death, biochemical failure (BF), locoregional recurrence (LRR), and distant metastasis (DM) in relatively young men with UIR-PC undergoing RP or high-dose IMRT. After adjustment for confounders, RP was found to be superior to high-dose IMRT in terms of the patients’ overall survival, BF, LRR, and DM.Purpose: To estimate the oncologic outcomes of radical prostatectomy (RP) and high-dose intensity-modulated radiotherapy (IMRT) with short-term androgen-deprivation therapy (ADT) in relatively young men with unfavorable intermediate-risk prostate cancer, as defined by the National Comprehensive Cancer Network (NCCN-UIR-PC). Patients and Methods: We enrolled relatively young men (≤65 years) from the Taiwan Cancer Registry who had been diagnosed as having NCCN-UIR-PC and who had received RP or high-dose IMRT (at least ≥72 Gy) with short-term ADT (4–6 months). After propensity score matching of the confounders, Cox proportional regression was used to model the time from the index date (i.e., date of diagnosis) to all-cause death, biochemical failure (BF), locoregional recurrence (LRR), and distant metastasis (DM). Results: The corresponding adjusted hazard ratios (95% confidence intervals) of the risk of all-cause death, BF, LRR, and DM were 2.76 (1.36–5.60, p = 0.0050), 2.74 (1.72–4.84, p < 0.0001), 1.28 (1.09–1.90, p = 0.0324), and 2.11 (1.40–4.88, p = 0.0052), respectively. Conclusions: RP is superior to high-dose IMRT with short-term ADT in terms of oncologic outcomes for relatively young men with UIR-PC.

Concurrent high-dose intensity-modulated radiotherapy and chemotherapy for unresectable locally advanced and metastatic pancreatic cancer: a pilot study

AbstractAim:To evaluate the efficacy of concurrent chemotherapy and high-dose (≥55 Gy) intensity-modulated radiotherapy (CCIMRT) in comparison with chemotherapy alone and intensity-modulated radiotherapy (IMRT) alone for unresectable locally advanced or metastatic pancreatic cancer.Methods:Forty-six patients with pancreatic cancer undergoing CCIMRT (n = 17), chemotherapy alone (n = 16) or IMRT alone (n = 13) were analysed. Overall survival (OS), locoregional progression-free survival (LRPFS) and gastrointestinal toxicities were evaluated. The median radiation dose was 60 Gy (range, 55–60) delivered in a median of 25 fractions (range, 24–30). Gemcitabine (GEM) alone, GEM + S-1, S-1 alone, FOLFIRINOX and GEM + nab-paclitaxel were used in CCIMRT and chemo-monotherapy.Results:The 1-year OS rate was 69% in the CCIMRT group, 27% in the chemotherapy group and 38% in the IMRT group (p = 0·12). The 1-year LRPFS rate was 73, 0 and 40% in the 3 groups, respectively (p = 0·012). Acute Grade ≥ 2 gastrointestinal toxicity (nausea, diarrhea) was observed in 12% (2/17) in the CCIMRT group, 25% (4/16) in the chemotherapy group and 7·7% (1/13) in the IMRT group (p = 0·38). Late Grade 3 gastrointestinal bleeding was observed in 6·3% (1/16) in the chemotherapy group.Conclusion:High-dose CCIMRT yielded acceptable toxicity and favorable OS and LRPFS.

Increased risk of disease progression in younger men: Analysis of factors predicting biochemical failure and castration-resistant prostate cancer after high-dose intensity-modulated radiation therapy for nonmetastatic prostate cancer

BackgroundThe aim of this study was to investigate the clinical significance of the effect of age on disease control in men who received high-dose intensity-modulated radiation therapy (IMRT) for nonmetastatic prostate cancer (NMPCa). MethodsNMPCa patients with favorable intermediate to very high-risk features (National Comprehensive Cancer Network risk classification) treated with IMRT at our institution between September 2000 and May 2011 were analyzed retrospectively. Treatment consisted of high-dose IMRT (74–78 Gy/37–39 fractions) combined with 6 months of neoadjuvant hormonal therapy. Multivariable analysis using Fine and Gray's regression model was performed to evaluate whether age at initiation of IMRT was associated with biochemical failure (BF) and castration-resistant prostate cancer (CRPC) progression. ResultsA total of 367 patients were analyzed. The median follow-up period was 8.8 years after IMRT. The 5- and 10-year BF rates were 22.1 and 31.7%, and those of CRPC rates were 4.5 and 12.6%, respectively. Multivariable analysis revealed that a younger age (cut-off: 70 years old) at the initiation of IMRT was significantly correlated with both a higher BF rate (hazard ratio: 1.691, P= 0.0064) and higher CRPC rate (hazard ratio: 2.579, P = 0.0079). ConclusionsYounger men with NMPCa had increased risks of BF and CRPC after high-dose IMRT, and may benefit from more intensive treatments. Our findings should be further tested in prospective studies.

Ultrahypofractionation Should be a Standard of Care Option for Intermediate-Risk Prostate Cancer

Ultrahypofractionation Should be a Standard of Care Option for Intermediate-Risk Prostate Cancer

High-dose intensity-modulated chemoradiotherapy in vulvar squamous cell carcinoma: Outcome and toxicity

IntroductionTo evaluate clinical outcomes, pattern of failure, and toxicity after high-dose intensity-modulated radiation therapy (IMRT) for advanced vulvar cancer. MethodsIn this IRB approved retrospective study, the charts of women with histologically confirmed, non-metastatic vulvar cancer consecutively treated at our institution from 2012 to 2018 were reviewed to identify patients that received high-dose IMRT with curative intent. The treatment compliance, toxicities, and patterns of failure were investigated. Actuarial local, regional and distant recurrence and survival were estimated using Kaplan-Meier method and compared using log rank test. ResultsTwenty-six patients were identified, 23 were unresectable, and 3 refused surgery. Fifteen patients (58%) had inguinal node metastases; 10(38%) had pelvic node metastases. Elective surgical staging of groins was performed in 9-patients. Median tumor dose was 65.4Gy. Concurrent platinum-based chemotherapy was administered in 22(84.6%) patients. Complete response (CR) was achieved in 21/26 (80.7%) patients. Five patients had persistent disease following treatment and one sustained recurrence 5-months following radiotherapy. All persistent or recurrent disease occurred inside the irradiated volume. Median follow-up was 19 months (3–52 months). Actuarial 1-year local, regional and distant controls were 72.4%, 85.4%, and 86%, respectively. One and 2-year overall survivals were 91% and 62%, respectively. Complete response at 3-months was a strong predictor for overall survival (1-yr OS 73% vs 27%, HR 7.1 (95% CI 1.2–44); p = 0.01). Lymph node metastases adversely affected overall survival (2-yr OS 49% vs. 83%, p = 0.09). Grade 3–4 late urinary and soft-tissue toxicity was seen in 5 patients. Tumor doses >66 Gy (p = 0.03) and prior pelvic radiotherapy (p = 0.002) predicted grade 3–4 toxicity. ConclusionHigh-dose IMRT for vulvar cancer achieves high rates of local control with acceptable dose dependent long-term toxicity.