Dose-escalated Intensity-modulated Radiotherapy Research Articles

Outcome of dose-escalated intensity-modulated radiotherapy for limited disease small cell lung cancer.

An optimal once-daily radiotherapy (RT) regimen is under investigation for definitive concurrent chemoradiotherapy (CCRT) in limited disease small cell lung cancer (LD-SCLC). We compared the efficacy and safety of dose escalation with intensity-modulated radiotherapy (IMRT). Between January 2016 and March 2021, patients treated with definitive CCRT for LD-SCLC with IMRT were retrospectively reviewed. Patients who received a total dose <50 Gy or those with a history of thoracic RT or surgery were excluded. The patients were divided into two groups (standard and dose-escalated) based on the total biologically effective dose (BED, α/β = 10) of 70 Gy. The chemotherapeutic regimen comprised four cycles of etoposide and cisplatin. One hundred and twenty-two patients were analyzed and the median follow-up was 27.8 months (range, 4.4 to 76.9 months). The median age of the patients was 63 years (range, 35 to 78 years) and the majority had a history of smoking (86.0%). The 1- and 3-year overall survival rates of the escalated dose group were significantly higher than those of the standard group (93.5% and 50.5% vs. 76.7% and 33.3%, respectively; p = 0.008), as were the 1- and 3-year freedom from in-field failure rates (91.4% and 66.5% vs. 73.8% and 46.9%, respectively; p = 0.018). The incidence of grade 2 or higher acute and late pneumonitis was not significantly different between the two groups (p = 0.062, 0.185). Dose-escalated once-daily CCRT with IMRT led to improved locoregional control and survival, with no increase in toxicity.

Preoperative Dose-Escalated Intensity-Modulated Radiotherapy (IMRT) and Intraoperative Radiation Therapy (IORT) in Patients with Retroperitoneal Soft-Tissue Sarcoma: Final Results of a Clinical Phase I/II Trial.

To report the final results of a prospective, one-armed, single-center phase I/II trial (NCT01566123). Between 2007 and 2017, 37 patients with primary or recurrent (N = 6) retroperitoneal sarcomas were enrolled. Treatment included preoperative IMRT of 45-50 Gy with a simultaneous integrated boost of 50-56 Gy, surgery and IORT. The primary endpoint was local control (LC) at 5 years. The most common histology was dedifferentiated liposarcoma (51%), followed by leiomyosarcoma (24%) and well-differentiated liposarcoma (14%). The majority of lesions were high-grade (FNCLCC G1: 30%, G2: 38%, G3: 27%, two missing). Five patients were excluded from LC analysis per protocol. The minimum follow-up of the survivors was 62 months (median: 109; maximum 162). IORT was performed for 27 patients. Thirty-five patients underwent gross total resection; the pathological resection margin was mostly R+ (80%) and, less often, R0 (20%). We observed 10 local recurrences. The 5-year LC of the whole cohort was 59.6%. Eleven patients received a dose > 50 Gy plus IORT boost; LC was 64.8%; the difference, however, was not significant (p = 0.588). Of 37 patients, 15 were alive and 22 deceased at the time of final analysis. The 5-year OS was 59.5% (68.8% per protocol). The primary endpoint of a 5-year LC of 70% was not met. This might be explained by the inclusion of recurrent disease and the high rate of G3 lesions and leiomyosarcoma, which have been shown to profit less from radiotherapy. Stratification by grading and histology should be considered for future studies.

PSMA-PET-guided dose-escalated volumetric arc therapy for newly diagnosed lymph node-positive prostate cancer: 5 Year outcomes following the FROGG and EviQ node-positive guidelines.

The Royal Australian and New Zealand College of Radiologists (RANZCR) Faculty of Radiation Oncology Genitourinary Group (FROGG) guidelines and online EviQ protocols incorporate prostate-specific membrane antigen (PSMA) positron emission tomography (PET)-guided dose-escalated intensity-modulated radiation therapy (DE-IMRT) for newly diagnosed lymph node (LN) positive prostate cancer. We evaluated late toxicity and efficacy outcomes following the FROGG and EviQ approach. Patients with LN-positive-only metastases on PSMA-PET imaging were offered curative therapy with 3 months neoadjuvant androgen deprivation therapy (ADT) followed by DE-IMRT and 3 years adjuvant ADT. IMRT was delivered via volumetric arc therapy (VMAT). We aimed to deliver 81 Gy in 45 fractions (Fx) to the prostate and PET-positive LNs, and 60 Gy in 45 Fx to elective pelvic nodes, contoured using the PIVOTAL guidelines. Forty-five patients were included. The median number of PET-positive nodes boosted was 2 (range 1-6) and median boost volume 1.16 cc (range 0.15-4.14). Seventeen (38%) patients had PET-positive nodes outside of PIVOTAL contouring guidelines. With 60 months median follow-up, disease-free, metastasis-free, prostate cancer-specific and overall survival were 88.1%, 95.3%, 100% and 91.5%. There were no in-field nodal failures. Late grade 1, 2 and 3 gastrointestinal toxicities occurred in 4%, 2% and 0% of patients, and genitourinary toxicity in 18%, 18% and 4%. Lower limb grade 2 lymphoedema occurred in three patients (7%). Outcomes following FROGG guidelines and EviQ are promising, with high long-term disease control and low toxicity. Contouring guidelines require modification due to the high rate of PET-positive nodes demonstrated beyond recommended coverage.

A Prospective Analysis of Toxicity Associated with Intraoperative, Real-Time Planned Low Dose Rate Brachytherapy or Intensity-Modulated Radiotherapy Boost for High/Intermediate Risk Prostate Cancer

<h3>Purpose/Objective(s)</h3> The ASCENDE-RT trial which used pre-planned brachytherapy boost (BT) reported worse treatment-related morbidity with BT vs dose-escalated intensity-modulated radiotherapy boost (DE-IMRT) for prostate radiation therapy (RT). However, toxicity is technique dependent and the outcomes of real-time intraoperative BT have not been well studied. We evaluate the toxicity profile of intraoperative, real-time planned BT vs DE-IMRT. <h3>Materials/Methods</h3> 402 patients treated from 2010-18 at our institution were included. Median dose for DE-IMRT was 79Gy. BT included IMRT to a median of 45Gy plus BT boost of 110 Gy. Patient-reported outcomes using the validated Prostate Cancer Symptom Indices and physician-graded CTCAE toxicity were prospectively collected from baseline to 2yrs post-RT. Clinically meaningful symptoms were defined as ≥Grade 2. Per institutional practice, an α-1 blocker is started prior to BT but not DE-IMRT boost. We report acute (0-6 months) & late (1 & 2yr) toxicity. Multivariable logistic regression calculated odds ratios (OR) for symptoms & controlled for hormone therapy, image guidance modality, risk category & age. <h3>Results</h3> At acute, 1-, & 2-yr time points 148, 108, 54 & 254, 214, 162 patients were available for BT & DE-IMRT analysis, respectively. Baseline and acute genitourinary (GU) or gastrointestinal (GI) symptoms did not differ between cohorts. For both modalities, PRO GI and GU symptom prevalence peaked acutely, declined over 1yr and returned near baseline by 2yrs (Table). At 2yrs, a difference in ≥Grade 2 CTCAE GU toxicity persisted (19% vs 2%, p = <0.001); urinary frequency (6% vs 0%, p = 0.02), & incontinence (9% vs 2%, p = 0.02) differed most. On MVA, BT had higher 2-yr GU symptoms for PRO (OR 32.0, 95%CI: 6.2-165, p < 0.0001) & CTCAE (2.2, 1.4-3.6, p = 0.0006). Cumulative incidence of CTCAE ≥Grade 3 events at 2yr were GU 3.4% vs 0%, p = 0.007 & GI 2.0% vs 2.0%, p = 1.0 for BT & DE-IMRT. <h3>Conclusion</h3> This large single institution series with prospectively collected PRO & CTCAE toxicity is one of the first to report outcomes for intraoperatively, real-time planned BT. Odds of GU symptoms ≥Grade 2 are elevated with BT but cumulative incidence of GU/GI CTCAE ≥Grade 3 toxicity at 2yr was <4% for BT & DE-IMRT. Our results may assist in counseling and suggest that among appropriately selected patients a BT boost with intraoperative planning is reasonably well tolerated.

Dose-Escalated Intensity-Modulated Radiotherapy for the Management of Locally Advanced Cervical Cancer.

ObjectiveIn this study, we aimed to assess the response and toxicity related to dose escalation in external beam radiation therapy (EBRT) using intensity-modulated radiation therapy (IMRT) with weekly concurrent cisplatin followed by de-escalated brachytherapy (BT) in locally advanced carcinoma cervix of International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIB-IIIC1.Materials and methodsFifty-two patients diagnosed with cervical cancer FIGO 2018 stage IIB-IIIC1 were treated with curative intent from November 2019 to October 2021. The dose of 50 Gy was prescribed for the primary tumor volume and elective pelvic nodal volume followed by a primary boost to a dose of 20 Gy. Gross lymph node (LN) of size >1 cm after EBRT completion received a sequential nodal boost of 10 Gy. All patients received concurrent cisplatin to a dose of 40 mg/m2 for a total of five to six weekly cycles. All patients received two fractions of BT to a dose of 6 Gy after EBRT completion. Radiation-induced acute toxicities were graded according to the Radiation Therapy Oncology Group (RTOG) criteria and hematologic toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE v4.0).ResultsA median follow-up of six months was available for the 40 eligible patients. All patients tolerated treatment with an acceptable toxicity profile. Grade III dermatitis, grade III gastrointestinal (GI) toxicity, and grade III genitourinary (GU) toxicity were seen in three (7.5%), six (17.5%), and three patients (7.5%) respectively. Grade I anemia was evident in all patients. At six months after EBRT completion, 37 patients (92.5%) had a complete response and only three patients (7.5%) had residual disease.ConclusionBased on our findings, patients with cervical cancer treated with dose-escalated IMRT have a satisfactory outcome with reasonably low levels of treatment-related acute GI and GU toxicities. The findings of the present study endorse the notion that the application of a high dose of external radiation to the pelvis by IMRT technique with image-guided delivery could be an acceptable alternative to the standard-dose management schedule.

Propensity score-matched analysis comparing dose-escalated intensity-modulated radiation therapy versus external beam radiation therapy plus high-dose-rate brachytherapy for localized prostate cancer

PurposeDose-escalated external beam radiation therapy (EBRT) and EBRT + high-dose-rate brachytherapy (HDR-BT) boost are guideline-recommended treatment options for localized prostate cancer. The purpose of this study was to compare long-term outcome and toxicity of dose-escalated EBRT versus EBRT + HDR-BT boost.MethodsFrom 2002 to 2019, 744 consecutive patients received either EBRT or EBRT + HDR-BT boost, of whom 516 patients were propensity score matched. Median follow-up was 95.3 months. Cone beam CT image-guided EBRT consisted of 33 fractions of intensity-modulated radiation therapy with simultaneous integrated boost up to 76.23 Gy (DMean). Combined treatment was delivered as 46 Gy (DMean) EBRT, followed by two fractions HDR-BT boost with 9 Gy (D90%). Propensity score matching was applied before analysis of the primary endpoint, estimated 10-year biochemical relapse-free survival (bRFS), and the secondary endpoints metastasis-free survival (MFS) and overall survival (OS). Prognostic parameters were analyzed by Cox proportional hazard modelling. Genitourinary (GU)/gastrointestinal (GI) toxicity evaluation used the Common Toxicity Criteria for Adverse Events (v5.0).ResultsThe estimated 10-year bRFS was 82.0% vs. 76.4% (p = 0.075) for EBRT alone versus combined treatment, respectively. The estimated 10-year MFS was 82.9% vs. 87.0% (p = 0.195) and the 10-year OS was 65.7% vs. 68.9% (p = 0.303), respectively. Cumulative 5‑year late GU ≥ grade 2 toxicities were seen in 23.6% vs. 19.2% (p = 0.086) and 5‑year late GI ≥ grade 2 toxicities in 11.1% vs. 5.0% of the patients (p = 0.002); cumulative 5‑year late grade 3 GU toxicity occurred in 4.2% vs. 3.6% (p = 0.401) and GI toxicity in 1.0% vs. 0.3% (p = 0.249), respectively.ConclusionBoth treatment groups showed excellent long-term outcomes with low rates of severe toxicity.

Short-term ADT and Dose-escalated IMRT in Patients With Intermediate-risk Prostate Cancer: Benefit or Caution?

In the era of dose-escalated prostate radiation therapy (RT), the use of androgen deprivation therapy (ADT) is undefined for intermediate-risk (IR) prostate cancer. There is growing concern of the risk of ADT to be detrimental to quality of life. This single-institution retrospective analysis aimed to evaluate outcomes of IR patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with or without concurrent/adjuvant short-term ADT. Data was collected from 260 consecutive patients treated with dose-escalated IMRT with daily image-guided RT for newly diagnosed IR prostate cancer. Biochemical recurrence-free survival (BCRFS), distant metastasis-free survival, prostate cancer-specific survival, and overall survival (OS) were calculated using Kaplan-Meier methodology. Median follow-up was 93 months. A total of 181 patients had unfavorable IR disease, and 36.2% (N=94) received ADT, with median ADT duration of 6 months. Seven-year BCRFS was 94.1% vs. 86.2% (P=0.067), for ADT and no ADT, respectively, and no difference in distant metastasis-free survival or prostate cancer-specific survival was observed. ADT was associated with significantly worse 7-year OS (80.0% vs. 91.3%, P=0.010). Analysis of the unfavorable IR cohort alone, showed similar results; 7-year BCRFS and 7-year OS in patients who received ADT versus no ADT were 93.7% vs. 85.9% (P=0.093), and 79.0% vs. 90.6% (P=0.019), respectively. In our 15-year experience treating IR prostate cancer with dose-escalated IMRT with daily image-guided RT, short-term concurrent ADT was associated with a statistically significant worse OS. Additional studies are needed to determine if ADT is beneficial or detrimental for patients with IR prostate cancer treated with dose-escalated radiation.

Comparison Between Dose-Escalated Intensity Modulated Radiation Therapy and 3-Dimensional Conformal Radiation Therapy for Salvage Radiation Therapy After Prostatectomy

PurposeTo compare long-term outcomes and late toxicity between patients treated with 3-dimensional conformal radiation therapy (3D-CRT) and with dose-escalated intensity modulated radiation therapy (IMRT) as salvage radiation therapy (SRT) after prostatectomy. Methods and MaterialsA total of 110 patients who had been treated at our institution between 2010 and 2018 with SRT for biochemical recurrence after radical prostatectomy were included. The patients were treated either by 3D-CRT with 64 Gy (59 patients) or by IMRT with 70 Gy (51 patients). The irradiation target was the prostate bed only (106 patients) or the prostate bed and pelvic region (4 patients). Twelve patients (11%) received concurrent androgen deprivation therapy. The differences in clinical outcomes and late gastrointestinal (GI) and genitourinary (GU) toxicity between the 3D-CRT and IMRT groups were retrospectively assessed. Toxicities were recorded using the Common Terminology Criteria for Adverse Events, version 5.0. Prostate-specific antigen (PSA) progression after SRT was defined as an increase in the serum PSA level of 0.2 ng/mL from the PSA nadir after SRT and confirmed by a second PSA measurement that was higher than the first. ResultsThe median follow-up time was 7.8 years for 3D-CRT (range:,0.3-9.2 years) and 3.1 years for IMRT (range, 0.4-7.2 years). There was no significant difference in the 4-year biochemical no-evidence-of-disease (bNED) rate between the 3D-CRT and IMRT groups (43.5% vs 52.1%; P = .20). Toxicity analysis showed no significant difference in late GI or GU toxicities of grade 2 or greater between the 3D-CRT and IMRT groups. The respective 4-year cumulative rates of toxicity in the 3D-CRT and IMRT groups were as follows: grade ≥2 GI toxicity, 8.8% and 4.4% (P = .42); grade ≥2 GU toxicity, 19.1% and 20.3% (P = .93); and grade ≥2 hematuria, 5.3% and 8.0% (P = .67). In the 3D-CRT group, the 8-year cumulative rates of GI toxicity, GU toxicity, and hematuria of grade 2 or greater were 8.8%, 28.4%, and 12.6%, respectively. ConclusionsDose-escalated IMRT showed no improvements in bNED or late toxicity compared with 3D-CRT. In addition, the results suggest that GU toxicity can occur after a long period (even after 6 years), whereas GI toxicity is seldom newly observed after 4 years.

Dose-escalated intensity-modulated radiotherapy in patients with locally advanced laryngeal and hypopharyngeal cancers: ART DECO, a phase III randomised controlled trial

BackgroundRadical (chemo)radiotherapy offers potentially curative treatment for patients with locally advanced laryngeal or hypopharyngeal cancer. We aimed to show that dose-escalated intensity-modulated radiotherapy (DE-IMRT) improved locoregional control. MethodsWe performed a phase III open-label randomised controlled trial in patients with laryngeal or hypopharyngeal cancer (AJCC III-IVa/b, TNM 7). Patients were randomised (1:1) to DE-IMRT or standard dose IMRT (ST-IMRT) using a minimisation algorithm, balancing for centre, tumour site, nodal status and chemotherapy use. DE-IMRT was 67.2 gray (Gy) in 28 fractions (f) to the primary tumour and 56Gy/28f to at-risk nodes; ST-IMRT was 65Gy/30f to primary tumour and 54Gy/30f to at-risk nodes. Suitable patients received 2 cycles of concomitant cisplatin and up to 3 cycles of platinum-based induction chemotherapy. The primary end-point was time to locoregional failure analysed by intention-to-treat analysis using competing risk methodology. FindingsBetween February 2011 and October 2015, 276 patients (138 ST-IMRT; 138 DE-IMRT) were randomised. A preplanned interim futility analysis met the criterion for early closure. After a median follow-up of 47.9 months (interquartile range 37.5–60.5), there were locoregional failures in 38 of 138 (27.5%) ST-IMRT patients and 42 of 138 (30.4%) DE-IMRT patients; an adjusted subhazard ratio of 1.16 (95% confidence interval: 0.74–1.83, p = 0.519) indicated no evidence of benefit with DE-IMRT. Acute grade 2 pharyngeal mucositis was reported more frequently with DE-IMRT than with ST-IMRT (42% vs. 32%). No differences in grade ≥3 acute or late toxicity rates were seen. ConclusionDE-IMRT did not improve locoregional control in patients with laryngeal or hypopharyngeal cancer.The trial is registered: ISRCTN01483375.

Volumetric-Modulated Arc Radiotherapy with Daily Image-Guidance Carries Better Toxicity Profile for Higher Risk Prostate Cancer.

Purpose:To compare radiotherapy-induced toxicity for localized prostate-cancer (PCa) treated with versus without daily image-guidance. Patients and Methods:We identified consecutive intermediate and high-risk localized PCa patients treated with definitive radiotherapy using intensity-modulated radiotherapy (IMRT) with variable duration of androgen-deprivation therapy (ADT) within 2015-2016 (Arm-A) and 2005-2007 (Arm-B). Arm-A cases received daily online imaging guidance (IGRT) using cone-beam computed tomography (CBCT) unlike Arm-B candidates with no daily IGRT. After reporting demographic, clinico-pathological features and treatment details, we compared acute (within 3 months post-therapy) and late RT-induced toxicities between study groups graded by RTOG/CTCAE criteria. Uni/multivariate analyses (UVA/MVA) were performed to identify independent predictors for RT-related side-effects. Results:We were able to identify 257 cases who met our inclusion criteria. Overall, median age was 73 years (48-85), 67% had intermediate-risk and 47% received ADT. Arm-A included 72 patients who received IMRT delivered using volumetric-modulated arc therapy (VMAT), whereas, Arm-B was formed of 185 cases who utilized step-and-shoot static IMRT. Clinico-pathological features and treatment details were non-different across study arms except that Arm-A had more Grade Group 3, higher median total dose (79.2 vs. 74 Gy) and more pelvic lymph-nodes RT (P<0.05). Although acute toxicity was similar across groups, Arm-B encountered higher late toxicity score, more intense late genitourinary side-effects (P=0.008), with non-different late lower-gastrointestinal toxicities. On MVA, lack of daily CBCT, African-American race and higher comorbidities were independently predictive for late toxicities. Conclusion:IMRT with daily CBCT permitted safe delivery of dose-escalated IMRT with improved toxicity profile for higher-risk prostate cancer.

Prospective evaluation of probabilistic dose-escalated IMRT in prostate cancer.

BackgroundCure- and toxicity rates after intensity-modulated radiotherapy (IMRT) of prostate cancer are dose-and volume dependent. We prospectively studied the potential for organ at risk (OAR) sparing and compensation of tumor movement with the coverage probability (CovP) concept.Patients and methodsTwenty-eight prostate cancer patients (median age 70) with localized disease (cT1c–2c, N0, M0) and intermediate risk features (prostate-specific antigen [PSA] < 20, Gleason score ≤ 7b) were treated in a prospective study with the CovP concept. Planning-CTs were performed on three subsequent days to capture form changes and movement of prostate and OARs. The clinical target volume (CTV) prostate and the OARs (bladder and rectum) were contoured in each CT. The union of CTV1–3 was encompassed by an isotropic margin of 7 mm to define the internal target volume (ITV). Dose prescription/escalation depended on coverage of all CTVs within the ITV. IMRT was given in 39 fractions to 78 Gy using the Monte-Carlo algorithm. Short-term androgen deprivation was recommended and given in 78.6% of patients.ResultsLong-term toxicity was evaluated in 26/28 patients after a median follow-up of 7.1 years. At last follow-up, late bladder toxicity (Radiation Therapy Oncology Group, RTOG) G1 was observed in 14.3% of patients and late rectal toxicities (RTOG) of G1 (7.1%) and of G2 (3.6%) were observed. No higher graded toxicity occurred. After 7.1 years, biochemical control (biochemically no evidence of disease, bNED) was 95.5%, prostate cancer-specific survival and the distant metastasis-free survival after 7.1 years were 100% each.ConclusionsCovP-based IMRT was feasible in a clinical study. Dose escalation with the CovP concept was associated by a low rate of toxicity and a high efficacy regarding local and distant control.

Dose-escalated intensity modulated radiation therapy in patients with locally-advanced vulvar cancer - does it increase response rate?

PurposeGOG 205 safely increased clinical (cCR) and pathologic complete response (pCR) in locally-advanced vulvar cancer through dose escalation using three-dimensional radiotherapy (RT). The aim of this study is to assess the response of dose-escalated intensity modulated radiotherapy (IMRT) in locally-advanced vulvar cancer. MethodsA retrospective review of patients treated with dose-escalated (≥ 55Gy) IMRT from 2012 to 2018 for locally-advanced vulvar cancer was performed. Patients treated with preoperative or definitive intent were included. Rates of cCR and pCR were assessed, and predictors of disease-free survival (DFS) were analyzed using the Kaplan Meier method with log rank test between groups and a parsimonious multivariate Cox model. ResultsMedian dose to the vulva was 66.0 Gy (Interquartile Range [IQR]: 66.0–68.0) for definitive and 59.4 Gy (IQR: 58.0–59.4) for preoperative IMRT. The overall rates of cCR and pCR were 76% and 70%, respectively. DFS at two years was 65% (95% Confidence Interval [CI] 50–80%) for all patients, 81% (95% CI 63% - 98%) for definitive IMRT, and 55% (95% CI 35% - 76%) for preoperative IMRT. On multivariate analysis, cCR predicted for disease-free survival (HR 0.21; 95% CI 0.06–0.76; p = 0.02), and pCR predicted for OS (HR 0.12; 95% CI 0.02–0.60; p = 0.01). Grade 3 acute and late RT toxicity was seen in 14 (29%) and 3 (6%) of patients, respectively. ConclusionDose-escalated IMRT for locally-advanced vulvar cancer is well tolerated, with rates of cCR and pCR that compare favorably with published data.

Concurrent cisplatin and dose escalation with intensity-modulated radiotherapy (IMRT) versus conventional radiotherapy for locally advanced head and neck squamous cell carcinomas (HNSCC): GORTEC 2004-01 randomized phase III trial

BackgroundConcurrent chemoradiotherapy (CRT) is the standard of care (SoC) in locally advanced (LA) head and neck squamous cell carcinomas (HNSCC). This trial was designed to test whether dose-escalated IMRT and cisplatin could improve locoregional control without increasing complications over 3D-radiotherapy. MethodsPatients were randomized between 70 Gy/35F in 7 weeks with 3D-RT (Arm A) versus 75 Gy/35F with IMRT (Arm B). Both arms received 50 Gy in 25 fractions followed by a sequential boost of 20 Gy/10F in Arm A and 25 Gy/10F to gross tumor volume in Arm B, as well as 3 cycles of cisplatin at 100 mg/m2 during RT. The primary endpoint was locoregional progression (LRP). Results188 patients were randomized: 85% oropharynx and 73% stage IVa. P16 status was documented for 137 oropharyngeal tumors with P16+ in 53 (39%) patients; and 90% were smokers. Median follow-up was 60.5 months. Xerostomia was markedly decreased in arm B (p < 0.0001). The 1-year grade ≥2 xerostomia (RTOG criteria) was 63% vs 23% and 3-year 45% vs 11% in arms A and B, respectively. Xerostomia LENT-SOMA scale was also reduced in arm B. Dose-escalated IMRT did not reduce LRP with an adjusted HR of 1.13 [95%CI = 0.64–1.98] (p = 0.68). Survival was not different (adjusted HR: 1.19 [95%CI = 0.78–1.81], p = 0.42). No interaction between p16 and treatment effect was found. ConclusionDose-escalated IMRT did not improve LRC in LA-HNSCC patients treated with concomitant CRT over standard 3D-RT. This trial reinforces the evidence showing IMRT reduces xerostomia in LA-HNSCC treated with radiotherapy.Clinicaltrial.gov: NCT00158678.

PSMA-PET guided dose-escalated volumetric arc therapy (VMAT) for newly diagnosed lymph node positive prostate cancer: Efficacy and toxicity outcomes at two years

Purpose/objectivesThere are no published reports of prostate specific membrane antigen (PSMA) positron emission tomography (PET) guided dose-escalated intensity-modulated radiation therapy (DE-IMRT) in newly diagnosed lymph node (LN) positive prostate cancer. We report early toxicity and efficacy outcomes with this approach. Materials/methodsPatients with newly diagnosed high-risk prostate cancer were staged using PSMA PET, computed tomography (CT) and bone scans. Patients with LN positive-only metastases were offered curative therapy using 3 months androgen deprivation therapy (ADT) followed by DE-IMRT (using volumetric arc therapy), and 3 years adjuvant ADT. All patients had fiducial marker insertion, with privately insured patients having spacer hydrogel insertion. PET and prostate magnetic resonance imaging were fused with the planning CT. We aimed to deliver 81 Gy in 45 fractions (Fx) to the prostate and PET-positive LNs, and 60 Gy in 45Fx to bilateral elective pelvic LNs. ResultsIn all, 46 patients were treated, with 83% Gleason 8–10, 67% T3/T4, median number of LNs 2 (range 1–6), and median PET-positive LN volume 1.14 cc (range 0.15–4.14). LNs were outside of standard contouring guidelines in 37% of patients. The mean PET-positive LN clinical target volume dose ranged from 73.3 to 85.9 Gy (median 83.6 Gy). With 24 months median follow-up, two year failure-free survival was 100%, and 2 year overall survival 95.7%. Acute grade 1 and 2 GI toxicity occurred in 48 and 11% of patients, and GU toxicity in 72 and 24%. Late grade 1, 2 and 3 GI toxicity occurred in 13, 2 and 0%, and GU toxicity 28, 13 and 4%. No toxicity was attributable to the high dose LN boost. ConclusionsPSMA PET-guided DE-IMRT up to 81 Gy to the prostate and involved LNs, and long term ADT, is a promising approach for newly diagnosed LN positive prostate cancer. LN contouring guidelines require re-evaluation in the era of PSMA PET imaging.

Dose-Escalated Intensity Modulated Radiation Therapy in Patients with Locally Advanced Vulvar Cancer- Does It Increase Response Rate?

The management for locally-advanced vulvar cancer includes preoperative and definitive chemoradiotherapy. By increasing dose from 47.6Gy to 57.6Gy, GOG 205 safely increased clinical (cCR) and pathologic complete response (pCR) to 64% and 50% from 48% and 31% in GOG 101. Intensity modulated radiotherapy (IMRT) has improved the tolerability of radiotherapy in vulvar cancer, such that the ongoing GOG 0279 is examining further dose-intensification to 64Gy with concurrent gemcitabine and cisplatin. The aim of the current study is to assess the response of dose-escalated IMRT in locally-advanced vulvar cancer. We performed a retrospective review of patients treated with dose-escalated (≥54Gy) IMRT from 2012-2018 for locally-advanced vulvar cancer. Patients treated with preoperative (n=30, 67%) or definitive intent (n=15, 33%) were included, while patients treated with adjuvant radiotherapy were excluded. Concurrent chemotherapy with weekly cisplatin (40mg/m2) was administered in 93%. Median dose to the vulva was 66.8 Gy (IQR: 66.0 Gy to 68.0 Gy) for definitive and 59.4 Gy (IQR: 58.0 Gy-61.2 Gy) for preoperative IMRT. Toxicity was graded using CTCAE v4.03. Predictors of disease free survival (DFS) were analyzed using the Kaplan Meier method with log rank test between groups and a parsimonious multivariate Cox multivariate model. p16 status was not analyzed as a variable, due to missing data for p16 in 69%. Of the included 45 patients: median age was 67 years, 60% were ≥ cT2, 53% were node-positive on PET imaging, and 57% were ≥ FIGO Stage IIIA. The overall rate of cCR was 78%, with a pCR rate for preoperative patients of 63%. At a median follow-up of 18 months (IQR: 7.7 – 33.7), the 2-year DFS was 65% (95%CI 49%-81%) for all patients, 84% (95%CI 62%-100%) for definitive IMRT, and 58% (95%CI 39%-78%) for preoperative IMRT. pCR was a significant predictor of DFS on both univariate [2-year DFS 83% (95%CI 65%-100%) versus 21% (95%CI 0%-46%), p <0.01] and on multivariate analysis (HR 0.28, 95% CI 0.08-0.96). There was no significant difference in DFS by RT dose, age, clinical nodal status, SUV, or presence of lichen sclerosis on multivariate analysis. Median treatment duration was 46 days (IQR: 45-50 days), with a treatment break required in 4 patients, 3 for reasons unrelated to RT and 1 for febrile neutropenia. Grade 3 acute RT toxicity was seen in 14 (31%) patients and consisted mainly of radiation dermatitis, pain, and GI. Grade 3 late RT toxicity was seen in 3 (7%) of patients: vaginal stricture (n=2) and perineal pain (n=1). Dose-escalated IMRT for locally advanced vulvar cancer was well tolerated with acceptable acute and chronic effects, with minimal treatment interruptions. cCR and pCR rates compared favorably with published data. pCR is a strong predictor of DFS and may serve as a viable endpoint for future clinical trial design in locally-advanced vulvar cancer.

P-162 - Dose-escalated intensity-modulated radiotherapy (IMRT) using a simultaneous integrated boost (SIB) in rectal cancer

P-162 - Dose-escalated intensity-modulated radiotherapy (IMRT) using a simultaneous integrated boost (SIB) in rectal cancer

Dose-Escalated Intensity Modulated Radiation Therapy for Prostate Cancer: 15-Year Outcomes Data

PurposeTo report 15-year outcomes for dose-escalated intensity modulated radiation therapy (IMRT) for localized prostate cancer (PC) by evaluating biochemical relapse, distant metastases, cancer-specific survival, and long-term toxicity. Methods and materialsA database search was conducted for the first cohort of patients treated at this institution with 81 or 86.4 Gy between 1996 and 1998 using IMRT. Toxicity data were scored according to the Common Terminology Criteria for Adverse Events version 3.0. Median follow-up was 11.6 years (range, 5-21 years). ResultsIn the study, 301 patients were treated with 81 Gy (n = 269, 89%) or 86.4 Gy (n = 32, 11%). Patients were analyzed by National Comprehensive Cancer Network risk group, with 29% low risk (LR), 49% intermediate risk (IR), and 22% high risk (HR). Late grade 3 gastrointestinal (GI) toxicity was seen in 3 patients (1.0%). No grade 4 GI toxicity events occurred. Median time from radiation therapy to late grade 3 GI toxicity was 2.9 years. One event occurred after 10 years. Late grade 3 and 4 genitourinary (GU) toxicity was seen in 6 (2.0%) and 1 (0.3%) patient, respectively. Median time to late grade 3+ GU toxicity was 5.5 years. Two events occurred after 10 years. In addition, 38 (12.6%) developed second primary malignancies (SPMs), 8 of which were in-field malignancies. Median time from radiation therapy to all SPM and in-field SPM was 10 years. The 15-year relapse-free survival was 76%, 65%, and 55% in the LR, IR, and HR groups, respectively. Distant metastases-free survival was 88%, 75%, and 63% for LR, IR, and HR patients, respectively. PC-specific mortality was 1.9%, 7.1%, and 12.2% for LR, IR, and HR patients. ConclusionsThis report represents the longest follow-up data set to our knowledge of patients treated with high-dose IMRT for PC. Our findings indicate that it is well tolerated with 1.0% and 2.3% incidence of long-term grade 3+ GI and GU toxicity, respectively. The cohort had excellent PC-specific survival.

Dose-Escalated Intensity Modulated Radiation Therapy for Prostate Cancer: 15-Year Outcomes Data

To report 15-year outcomes data for dose-escalated IMRT for localized prostate cancer (PC) by evaluating biochemical relapse, distant metastases (DM), overall survival, and long-term toxicity. A database search was conducted for the first cohort of patients treated at this institution with 81 or 86.4 Gy between 1996 and 1998 using IMRT. Toxicity data was scored according to the Common Terminology Criteria for Adverse Events Version 3.0. The median follow-up was 11.6 years (range 5 to 21 years). During this time, 301 patients were treated with 81 Gy (n = 269, 89%) or 86.4 Gy (n = 32, 11%). Patients were also analyzed by NCCN risk group, with 29% low risk (LR) patients, 49% intermediate risk (IR), and 22% high risk (HR). Late grade 3 gastrointestinal (GI) toxicity was seen in 3 patients (1.0%). All 3 cases were due to rectal bleeding requiring transfusion, and 1 required embolization. No grade 4 GI toxicity events occurred. Median time from RT to late grade 3 GI toxicity was 2.9 years, and 1 event occurred after 10 years. Late grade 3 and 4 genitourinary (GU) toxicity were seen in 6 (2.0%) and 1 (0.3%) patient, respectively. Grade 3 toxicities were due to stricture requiring procedural intervention or hematuria/cystitis requiring bladder irrigation/debridement. Grade 4 toxicity was due to persistent hematuria ultimately requiring cytectomy. Median time to late grade 3+ GU toxicity was 5.5 years, and 2 events occurred after 10 years. 38 (12.6%) had second primary malignancies (SPM) diagnosed after prostate RT, 8 (22%) of which were in-field malignancies including colorectal and bladder cancers and 1 case of pubic bone sarcoma. Median time from RT to all SPM and in-field SPM was 10 years. The 15-year PSA relapse-free survival was 76%, 65%, and 55% in the LR, IR, and HR groups, respectively. DM-free survival was 88%, 75%, and 63% for LR, IR, and HR patients. Prostate cancer-specific mortality was 1.9%, 7.1%, and 12.2% for LR, IR, and HR risk patients. This report represents the longest follow-up data set to our knowledge of patients treated with high-dose IMRT for PC. Our findings indicate that it is well tolerated with 1.0% and 2.3% incidence of long-term grade 3+ GI and GU toxicity, respectively. The cohort had excellent PC-specific survival.

Long-term outcomes of dose-escalated intensity modulated radiation therapy alone without androgen deprivation therapy for patients with intermediate and high-risk prostate cancer

ObjectiveThe addition of androgen deprivation therapy (ADT) to conventional radiation therapy improves overall survival (OS) in intermediate- and high-risk prostate cancer. The benefit of ADT to added to dose-escalated radiotherapy is less clear. The aim of this study was to report disease control outcomes and to identify prognostic variables associated with favorable outcomes in patients with intermediate- and high-risk prostate cancer treated with dose-escalated radiation therapy without ADT. Methods and materialsFrom September 2001 to March 2010, 127 patients with intermediate- or high-risk prostate cancer were treated with dose-escalated radiation otherapy without ADT. Biochemical recurrence-free survival (bRFS), distant metastases-free survival (DMFS), prostate cancer–specific mortality, and OS were assessed. Univariate and multivariate analyses using Cox regression modeling were performed. ResultsThe median follow-up was 6.5 years, and the 5-year estimated bRFS, DMFS, prostate cancer–specific mortality, and OS for all patients was 89%, 96.1%, 98.4%, and 96.9% respectively. On multivariate analysis, factors that predict bRFS include risk group and PSA nadir, and factors that predict DMFS include perineural invasion, risk group, and PSA nadir. ConclusionsPatients with favorable intermediate-risk cancer could likely be treated with dose-escalated radiation therapy without ADT. Patients with high-risk and unfavorable intermediate-risk cancer, perineural invasion, and PSA nadir ≥1ng/dL had worse outcomes and likely need distinct therapeutic approaches.

Randomized Trial of Hypofractionated Dose-Escalated Intensity Modulated Radiation Therapy Versus Conventionally Fractionated Intensity Modulated Radiation Therapy for Localized Prostate Cancer

Randomized Trial of Hypofractionated Dose-Escalated Intensity Modulated Radiation Therapy Versus Conventionally Fractionated Intensity Modulated Radiation Therapy for Localized Prostate Cancer