Image-guided Hypofractionated Radiotherapy Research Articles

Image-guided moderately hypofractionated radiotherapy for localized prostate cancer: a multicentric retrospective study (IPOPROMISE)

BackgroundModerate hypofractionated radiotherapy is a treatment option for the cure of localized prostate cancer (PCa) patients based on the results of randomized prospective trials, but there is a clinical concern about the relatively short length of follow-up, and real-world results on outcome and toxicity based on cutting-edge techniques are lacking. The objective of this study is to present the long-term results of a large multicentric series.Materials and methodsWe retrospectively evaluated 1325 PCa patients treated with daily volumetric image-guided hypofractionated radiotherapy between 2007 and 2020 in 16 Centers. For survival endpoints, we used Kaplan–Meier survival curves and fitted univariate and multivariable Cox’s proportional hazards regression models to study the association between the clinical variables and each survival type.ResultsAt the end of the follow-up, 11 patients died from PCa. The 15-year values of cancer-specific survival (CSS) and biochemical relapse-free survival (b-RFS) were 98.5% (95%CI 97.3–99.6%) and 85.5% (95%CI 81.9–89.4%), respectively. The multivariate analysis showed that baseline PSA, Gleason score, and the use of androgen deprivation therapy were significant variables for all the outcomes. Acute gastrointestinal (GI) and genitourinary (GU) toxicities of grade ≥ 2 were 7.0% and 16.98%, respectively. The 15-year late grade ≥ 2 GI and GU toxicities were 5% (95%CI 4–6%) and 6% (95%CI 4–8%), respectively.ConclusionReal-world long-term results of this multicentric study on cutting-edge techniques for the cure of localized PCa demonstrated an excellent biochemical-free survival rate of 85.5% at 15 years, and very low rates of ≥ G3 late GU and GI toxicity (1.6% and 0.9% respectively), strengthening the results of the available published trials.

Efficacy and Safety of Image-Guided Hypofractionated Radiotherapy for Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

To evaluate the efficacy and safety of image-guided 10-fraction hypofractionated radiotherapy (RT) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). Between 2016 and March 2022, 69 HCC with PVTT patients received RT (40-50Gy/10fx) in our institutions. The median prescribed dose of 50 Gy (range, 40-50 Gy, BED10; 56-75 Gy10) was delivered in 10 fractions in all patients. Follow-up imaging was performed at three-month intervals after the completion of RT. The extent of PVTT was described according to the Liver Cancer Study Group of Japan classification: Vp0 = no PVTT, Vp1 = segmental portal vein branch, Vp2 = right/left anterior/posterior portal vein, Vp3 = right/left portal vein and Vp4 = main portal vein. Response evaluation was performed using response evaluation criteria in solid tumors, version 1.1. Freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) were calculated from the start date of RT. In this cohort, 4.3% of patients had Vp1 PVTT, 20.3% had Vp2, 37.7% had Vp3, and 37.7% had Vp4. The median PTV volume was 105.3 cc (interquartile range [IQR], 74.1-179.4 cc). Fifty-two (75.4%) patients received 50 Gy in 10 fractions. With a median follow-up of 10.2 months (IQR, 6-21 months), the median OS was 18.5 months, and 1-year FFLP, PFS, and OS rates were 84.8%, 26.9%, and 62.2% respectively. At 3 months after RT, 13.0% had a complete response, 36.2% had a partial response, 46.4% had a stable disease and 4.4% had a progressive disease. In the multivariate analysis, AFP ≥ 600 IU/ml (HR 2.06, p = 0.03), Child-Pugh Class B or C (HR 2.30, p = 0.02), and modified Union for International Cancer Control (mUICC) stage IVA or IVB (4.05, p = 0.02) were significantly related to OS. During the follow-up period, there were 2 (2.8%) cases of grade ≥3 toxicity: grade 3 AST/ALT elevation (n = 1), and acute cholangitis (n = 1). Hypofractionated RT demonstrated promising local PVTT control with acceptable toxicity. These data suggest that 10-fraction image-guided hypofractionated RT (BED10 = 56-75 Gy10) is a feasible treatment option for PVTT in HCC patients.

Lung-heart toxicity in a randomized clinical trial of hypofractionated image guided radiation therapy for breast cancer.

TomoBreast hypothesized that hypofractionated 15 fractions/3 weeks image-guided radiation therapy (H-IGRT) can reduce lung-heart toxicity, as compared with normofractionated 25-33 fractions/5-7 weeks conventional radiation therapy (CRT). In a single center 123 women with stage I-II operated breast cancer were randomized to receive CRT (N=64) or H-IGRT (N=59). The primary endpoint used a composite four-items measure of the time to 10% alteration in any of patient-reported outcomes, physician clinical evaluation, echocardiography or lung function tests, analyzed by intention-to-treat. At 12 years median follow-up, overall and disease-free survivals between randomized arms were comparable, while survival time free from alteration significantly improved with H-IGRT which showed a gain of restricted mean survival time of 1.46 years over CRT, P=0.041. The finding establishes TomoBreast as a proof-of-concept that hypofractionated image-guided radiation-therapy can improve the sparing of lung-heart function in breast cancer adjuvant therapy without loss in disease-free survival. Hypofractionation is advantageous, conditional on using an advanced radiation technique. Multicenter validation may be warranted. https://clinicaltrials.gov/ct2/show/NCT00459628. Registered 12 April 2007.

Comparing Outcomes of Oligometastases Treated with Hypofractionated Image-Guided Radiotherapy (HIGRT) with a Simultaneous Integrated Boost (SIB) Technique versus Metastasis Alone: A Multi-Institutional Analysis.

Simple SummaryHypofractionated image-guided radiotherapy (HIGRT) is a common method in which high doses of radiation are delivered to treat oligometastatic disease. We have previously reported on the clinical outcomes of treating oligometastases with radiation using an elective simultaneous integrated boost technique (SIB), delivering higher doses to known metastases and reduced doses to adjacent bone or nodal basins. Here we compare outcomes of oligometastases receiving radiation targeting metastases alone (MA) versus those treated via an SIB. Both SIB and MA irradiation of oligometastases achieved high rates of tumor metastases control and similar pain control. Further investigation of this technique with prospective trials is warranted.Purpose: We previously reported on the clinical outcomes of treating oligometastases with radiation using an elective simultaneous integrated boost technique (SIB), delivering higher doses to known metastases and reduced doses to adjacent bone or nodal basins. Here we compare outcomes of oligometastases receiving radiation targeting metastases alone (MA) versus those treated via an SIB. Methods: Oligometastatic patients with ≤5 active metastases treated with either SIB or MA radiation at two institutions from 2013 to 2019 were analyzed retrospectively for treatment-related toxicity, pain control, and recurrence patterns. Tumor metastasis control (TMC) was defined as an absence of progression in the high dose planning target volume (PTV). Marginal recurrence (MR) was defined as recurrence outside the elective PTV but within the adjacent bone or nodal basin. Distant recurrence (DR) was defined as any recurrence that is not within the PTV or surrounding bone or nodal basin. The outcome rates were estimated using the Kaplan–Meier method and compared between the two techniques using the log-rank test. Results: 101 patients were treated via an SIB to 90 sites (58% nodal and 42% osseous) and via MA radiation to 46 sites (22% nodal and 78% osseous). The median follow-up among surviving patients was 24.6 months (range 1.4–71.0). Of the patients treated to MA, the doses ranged from 18 Gy in one fraction (22%) to 50 Gy in 10 fractions (50%). Most patients treated with an SIB received 50 Gy to the treated metastases and 30 Gy to the elective PTV in 10 fractions (88%). No acute grade ≥3 toxicities occurred in either cohort. Late grade ≥3 toxicity occurred in 3 SIB patients (vocal cord paralysis and two vertebral body compression), all related to the high dose PTV and not the elective volume. There was similar crude pain relief between cohorts. The MR-free survival rate at 2 years was 87% (95% CI: 70%, 95%) in the MA group and 98% (95% CI: 87%, 99%) in the SIB group (p = 0.07). The crude TMC was 89% (41/46) in the MA group and 94% (85/90) in the SIB group. There were no significant differences in DR-free survival (65% (95% CI: 55–74%; p = 0.24)), disease-free survival (60% (95% CI: 40–75%; p = 0.40)), or overall survival (88% (95% CI: 73–95%; p = 0.26)), between the MA and SIB cohorts. Conclusion: Both SIB and MA irradiation of oligometastases achieved high rates of TMC and similar pain control, with a trend towards improved MR-free survival for oligometastases treated with an SIB. Further investigation of this technique with prospective trials is warranted.

The Role of Hypofractionated Radiation Therapy in the Management of Unresectable Hepatocellular Carcinoma (HCC)

Management of HCC without surgical resection or transplantation is poorly defined with no standard. Stereotactic body radiation therapy (SBRT) or hypofractionated image-guided radiotherapy (HIGRT), is an evolving, non-invasive, therapeutic option for patients with HCC delivering ablative doses with modest toxicity.We retrospectively identified all patients with unresectable, non-metastatic HCC treated with SBRT/HIGRT who presented to our University and Veterans Affairs (VA) radiation oncology departments from 2013 to 2019. Primary study endpoints included freedom from local progression, progression free survival, overall survival, and treatment-related toxicity.149 patients were included in our analysis with median delivered radiation dose of 50 Gy in 5 fractions. This included a total of 172 treatment courses, as 21 patients received more than one course (19 patients received 2 courses; 2 patients received 3 courses). Twenty-two of the re-treatment courses were to previously unirradiated lesions, while one course was delivered to a previously treated lesion exhibiting local progression. Sixty-nine percent (69%) of patients were Child-Pugh A and 89% had a baseline ALBI grade of 1-2 prior to treatment. A majority of patients (59%) had a single lesion with a median size of 2.70 cm (Q1 2.00, Q3 3.95). Fifty-seven percent (57%) of patients received a biologically effective dose (BEDα/β = 10) of at least 75 Gy and 48% of patients had undergone prior liver-directed therapy. All patients completed their intended treatment course with 1 patient (0.7%) experiencing Grade 3+ acute and 4 patients (2.6%) experiencing Grade 3+ late toxicities. Fifteen treatment courses (8.7%) resulted in non-classical radiation-induced liver disease (RILD), defined as an increase of 2 or more points in Child-Pugh score following radiation. With median follow up of 40 months, median overall survival was 25 months (95% CI 18-30 months). The 2-year freedom from local progression was 75% (95% CI 65-83%) overall, 64% (95% CI 48-77%) among patients who received BED ≤75 Gy and 86% (95% CI 72-93%) among those who received BED > 75 Gy. Median progression free survival was not reached. During the study period, 8.1% of patients developed regional nodal progression and 18.8% developed distant metastatic disease (42.9% osseous, 50.0% lung, 46.4% soft tissue/peritoneal/other involvement; multiple patients with more than one site of metastatic involvement).SBRT/HIGRT results in high rates of local control with minimal treatment related toxicities. Randomized, prospective trials should seek to establish SBRT/HIGRT as a standard local therapeutic option for patients with unresectable, non-metastatic HCC.

Treatment Strategies for Oligometastatic Breast Cancer.

Oligometastatic breast cancer, typically defined as the presence of 1-5 metastases, represents an intermediate state between locally advanced and widely metastatic disease. Emerging research suggests that oligometastatic cancer has a unique molecular signature distinct from widely metastatic disease, and that it carries a superior prognosis. Owing to its more limited capacity for widespread progression, oligometastatic disease may benefit from aggressive ablative therapy to known metastases. Options for ablation include surgical excision, radiofrequency ablation, and hypofractionated image-guided radiotherapy (HIGRT). The phase II SABR-COMET trial, which enrolled patients with oligometastatic disease of multiple histologies and randomized them to HIGRT vs. standard of care, found a notable survival advantage in favor of HIGRT. Other data suggest that HIGRT may synergize with immunotherapy by releasing powerful cytokines that increase anti-tumor immune surveillance and by recruiting tumor infiltrating lymphocytes, helping to overcome resistance to therapy. There are many ongoing trials exploring the role of ablative therapy, most notably HIGRT, with or without immunotherapy, for the treatment of oligometastatic breast cancer.We believe that patients with oligometastatic breast cancer should be offered enrollment on prospective clinical trials when possible. Outside the context of a clinical trial, we recommend that select patients with oligometastatic breast cancer be offered treatment with a curative approach, including ablative therapy to all sites of disease if it can be safely accomplished. Currently, selection criteria to consider for ablative therapy include longer disease-free interval from diagnosis to metastasis (>2 years), fewer metastases, and fewer involved organs. Undoubtedly, new data will refine or even upend our understanding of the definition and optimal management of oligometastatic disease.

PO-1214 Toxicity profile of adjuvant hypofractionated Image-Guided Radiotherapy in biliary tract carcinoma

PO-1214 Toxicity profile of adjuvant hypofractionated Image-Guided Radiotherapy in biliary tract carcinoma

Moderate hypofractionated post-prostatectomy radiation therapy is feasible and well tolerated: experience from a single tertiary cancer centre.

Conventional post-prostatectomy radiation therapy comprises 6.5-8weeks of treatment, therefore, hypofractionated and shortened schemes arouse increasing interest. We describe our experience regarding feasibility and clinical outcome of a post-prostatectomy moderate hypofractionated image-guided radiotherapy schedule MATERIALS AND METHODS: From Oct 2015-Mar 2020, 113 patients, median age of 62years-old (range 45-76) and prostate adenocarcinoma of low risk (30%), intermediate risk (49%) and high risk (21%) were included for adjuvant (34%) or salvage radiation therapy (66%) after radical prostatectomy (RP). All patients underwent radiotherapy with image-guided IMRT/VMAT to a total dose of 62.5Gy in 2.5Gy/fraction in 25 fractions. Sixteen patients (14%) received concomitant androgen deprivation therapy. With a median follow-up of 29months (range 3-60months) all patients but three are alive. Eleven patients (10%) developed exclusive biochemical relapse while 19 patients (17%) presented macroscopically visible relapse: prostatectomy bed in two patients (2%), pelvic lymph nodes in 13 patients (11.5%) and distant metastases in four patients (4%). The 3years actuarial rates for OS, bFRS, and DMFS were 99.1, 91.1 and 91.2%, respectively. Acute and late tolerance was satisfactory. Maximal acute genitourinary (AGU) toxicity was G2 in 8% of patients; maximal acute gastrointestinal (AGI) toxicity was G2 in 3.5% of patients; maximal late genitourinary (LGU) toxicity was G3 in 1% of patients and maximal late gastrointestinal (LGI) toxicity was G2 in 2% of patients. There were no cases of severe acute or late toxicity. No relationship was found between acute or late GI/GU adverse effects and dosimetric parameters, age, presence of comorbidities or concomitant treatments. Hypofractionated radiotherapy (62.5Gy in 25 2.5Gy fractions) is feasible and well tolerated with low complication rates allowing for a moderate dose-escalation that offers encouraging clinical results for biochemical control and survival in patients with prostate cancer after radical prostatectomy.

Oligometastatic breast cancer: where are we now and where are we headed?—a narrative review

Metastatic breast cancer has traditionally been considered incurable, with treatments focused on systemic therapies and palliative local treatment. However, evidence is emerging that in some patients with limited metastatic disease, or "oligometastatic disease," often defined as five or fewer metastases diagnosed on imaging, aggressive metastasis-directed therapy (MDT) with surgery and/or hypofractionated image-guided radiation therapy (HIGRT) improves outcomes and may even be curative. This practice is becoming more common as evidence has grown to support the approach and as technology has made it more feasible. Treatment of certain oligometastatic breast cancers in particular (i.e., hormone receptor positive and bone-only metastases) may be especially useful given the long natural history of the disease in some of these patients. Recently, high quality data supporting ablative MDT in patients with oligometastatic disease has emerged from randomized trials for specific sites such as non-small cell lung cancer and prostate cancer, as well as from histology agnostic studies (i.e., SABR-COMET). However, randomized data in breast cancer specifically is currently lacking. Retrospective series and subgroup analysis from prospective trials have demonstrated improved outcomes with MDT for oligometastatic breast cancer. The ongoing phase II/III NRG BR002 trial seeks to provide the first randomized data to determine whether MDT in oligometastatic breast cancer improves outcomes. This may be especially important as improved systemic therapies such as targeted agents and immunotherapy prolong the disease course. Alternatively, if improved systemic therapies render patients disease free, MDT may not be necessary and only adds toxicity. However, MDT may also provide non-curative benefits for patients such as palliation of symptoms and extended time off systemic therapy. For now, aggressive MDT for certain favorable subgroups of oligometastatic breast cancer such as those with few metastases, hormone positive disease, and/or bone-only metastases is reasonable and may improve outcomes. We eagerly anticipate the results of NRG BR002 to further clarify the role of ablative therapy to all sites of disease in these patients.

A Pilot Study of Atezolizumab Plus Hypofractionated Image Guided Radiation Therapy for the Treatment of Advanced Non-Small Cell Lung Cancer

Preclinical data and subset analyses from immunotherapy clinical trials indicate that prior radiation therapy was associated with better progression-free survival and overall survival when combined with immune checkpoint inhibitors in patients with non-small cell lung cancer. We present a prospective study of hypofractionated image guided radiation therapy (HIGRT) to a single site of metastatic disease concurrently with atezolizumab in patients with metastatic non-small cell lung cancer. Patients meeting eligibility criteria received 1200 mg of atezolizumab intravenously every 3 weeks with concurrent 3- or 5-fraction HIGRT starting no later than the second cycle. The 3-fraction regimen employed a minimum of 8 Gy per fraction compared with 6 Gy for the 5-fraction regimen. Imaging was obtained every 12 weeks to assess response. From October 2015 to February 2017, 12 patients were enrolled in the study (median age 64; range, 55-77 years). The best response by the Response Evaluation in Solid Tumors criteria was partial response in 3 and stable disease in 3, for a disease control rate of 50%. Five patients had a grade 3 immune-related adverse event, including choreoretinitis (n = 1), pneumonitis (n = 1), transaminitis (n = 1), fatigue (n = 1), and peripheral neuropathy (n = 1). The median progression-free survival was 2.3 months, and the median overall survival was 6.9 months (range, 0.4-not reached). There was no clear association between peripheral blood T cell repertoire characteristics at baseline, PD-L1, or tumor mutations and response or outcome. One long-term survivor exhibited oligoclonal T cell populations in a baseline tumor biopsy that were consistently detected in peripheral blood over the entire course of the study. HIGRT plus atezolizumab resulted in an overall response rate of 25% and disease control rate of 50% in this pilot study. The incidence of grade 3 adverse events was similar to that of atezolizumab alone. Alhough it was a pilot study with limited sample size, the results generated hypotheses worthy of further investigation.

Imaging & Biomarker Correlates on Outcomes in a Phase II Trial of Neoadjuvant Gemcitabine/Nab-Paclitaxel and Hypofractionated Image-Guided Radiotherapy (HIGRT) in Potentially Resectable Pancreas Cancer

Pancreas cancer is a leading cause of cancer-related death with high rates of local and distant failures. Despite ongoing research, the optimal management of potentially resectable pancreas cancer remains unknown. We evaluated associations of changes in tumor size and blood biomarkers on outcomes in a phase II trial of neoadjuvant gemcitabine/nab-paclitaxel and HIGRT in patients with potentially resectable pancreas cancer. Patients with newly diagnosed potentially resectable pancreas cancer were prospectively enrolled on this study. Patients received 2 cycles of neoadjuvant gemcitabine/nab-paclitaxel followed by HIGRT (5 Gy x 5). Patients were restaged following chemotherapy and after HIGRT. Patients were considered for surgery 3-6 weeks post-HIGRT. Potential associations between changes in tumor size, tumor markers (CEA, CA 19-9), and outcomes (R0 resection, PFS, OS) were assessed using t-tests, proportional hazards regression, and the log rank test. Log transformation was used in analyses of CEA and CA 19-9. 40 patients (9 resectable, 31 borderline resectable) were enrolled from 2015-2018. Median age was 67 (range 38-81). Median follow-up was 24 months. 35 patients completed neoadjuvant treatment and 24 underwent resection. Most patients who did not undergo surgery had developed metastases (n=13). Median baseline tumor dimensions were 2.7 cm (greater) and 2.3 cm (smaller). 34 patients’ (85%) baseline CA 19-9 was >40 U/mL (median 150). Tumor size in the greater dimension was correlated with higher CA 19-9 (r=0.38; p=0.02). At restaging, tumor size was increased, stable, and decreased in 3, 17, and 19 patients, respectively, following chemotherapy, and in 5, 23, and 7 patients following HIGRT. CA 19-9 was increased in 5 and decreased/stable in 33 patients following chemotherapy, and increased in 5 and decreased/stable in 29 patients following HIGRT. Change in tumor size was associated with a significant difference in OS (median 7.6, 24.4, and 24.3 mo for increased, stable, decreased; p=0.006) and a trend towards a difference in PFS (median 4.8, 13.0, and 11.0 mo for increased, stable, decreased; p=0.11). Size following HIGRT was not associated with differences in OS or PFS. CEA was highly variable and associations with OS and PFS could not be accurately determined. Decrease in CA 19-9 was associated with improved PFS following chemotherapy (HR 0.53, 95% CI 0.39-0.83) and HIGRT (HR 0.39, 95% CI 0.25-0.62) and improved OS following chemotherapy (HR 0.41, 95% CI 0.24-0.71) and HIGRT (HR 0.24, 95% CI 0.12-0.50). In this phase II trial, changes in tumor size and CA 19-9 were associated with survival outcomes and may assist in adapting neoadjuvant therapy in potentially resectable pancreas cancer to optimize and personalize patient care.

Treatment of Adrenal Metastases with Conventional or Hypofractionated Image-guided Radiation Therapy - Patterns and Outcomes.

Metastases involving the adrenal glands can be treated surgically or with radiation therapy. Retrospective studies indicate that radiotherapy for this indication is safe, well-tolerated and associated with symptom palliation and good local control. We conducted this analysis to report on patterns and outcomes of patients with adrenal metastases treated with hypo- or conventionally fractionated image-guided radiotherapy. Patients with adrenal metastases from solid tumors treated at our department between 01/2010-12/2017 were reviewed. A total of 22 lesions were treated in 18 patients with a median dose of 35 Gy (20-60 Gy) in a median number of 7 (4-25) fractions. No grade ≥3 toxicity occurred. Median overall survival was 11.9 months. Five local failures occurred (22.7%). Lesion sizes or radiation dose were not correlated with local control. Patients treated for oligometastatic and oligoprogressive disease had a median overall survival of 33 and 6.5 months, respectively (palliative/polymetastatic: 1.6 months). Symptoms improved in all patients treated for clinically apparent lesions. Stereotactic radiotherapy of adrenal metastases was safe and effective in patients with oligometastases or oligoprogression. In palliative patients, short-course radiotherapy complemented with supportive care should be preferred.

Classification for long-term survival in oligometastatic patients treated with ablative radiotherapy: A multi-institutional pooled analysis.

BackgroundRadiotherapy is increasingly used to treat oligometastatic patients. We sought to identify prognostic criteria in oligometastatic patients undergoing definitive hypofractionated image-guided radiotherapy (HIGRT).MethodsExclusively extracranial oligometastatic patients treated with HIGRT were pooled. Characteristics including age, sex, primary tumor type, interval to metastatic diagnosis, number of treated metastases and organs, metastatic site, prior systemic therapy for primary tumor treatment, prior definitive metastasis-directed therapy, and systemic therapy for metastasis associated with overall survival (OS), progression-free survival (PFS), and treated metastasis control (TMC) were assessed by the Cox proportional hazards method. Recursive partitioning analysis (RPA) identified prognostic risk strata for OS and PFS based on pretreatment factors.Results361 patients were included. Primary tumors included non-small cell lung (17%), colorectal (19%), and breast cancer (16%). Three-year OS was 56%, PFS was 24%, and TMC was 72%. On multivariate analysis, primary tumor, interval to metastases, treated metastases number, and mediastinal/hilar lymph node, liver, or adrenal metastases were associated with OS. Primary tumor site, involved organ number, liver metastasis, and prior primary disease chemotherapy were associated with PFS.OS RPA identified five classes: class 1: all breast, kidney, or prostate cancer patients (BKP) (3-year OS 75%, 95% CI 66–85%); class 2: patients without BKP with disease-free interval of 75+ months (3-year OS 85%, 95% CI 67–100%); class 3: patients without BKP, shorter disease-free interval, ≤ two metastases, and age < 62 (3-year OS 55%, 95% CI 48–64%); class 4: patients without BKP, shorter disease-free interval, ≥ three metastases, and age < 62 (3-year OS 38%, 95% CI 24–60%); class 5: all others (3-year OS 13%, 95% CI 5–35%). Higher biologically effective dose (BED) (p < 0.01) was associated with OS.ConclusionsWe identified clinical factors defining oligometastatic patients with favorable outcomes, who we hypothesize are most likely to benefit from metastasis-directed therapy.

Moderate Hypofractionation in Patients with Low-risk Prostate Cancer: Long-term Outcomes.

To evaluate outcomes in patients with low-risk prostate cancer treated with hypofractionated radiotherapy (HyRT). Between April 2004 and December 2015, 175 patients with low-risk prostate cancer were treated with HyRT 60 Gy in 20 fractions with or without image guidance and reduction of margin from clinical target volume to planning target volume. The median follow-up was 66 months. The 8-year overall survival for the whole patient cohort was 88.9%. The 8-year biochemical no evidence of disease was higher in patients treated with image-guided HyRT (98.8% vs. 88%, p=0.023). During treatment, patients treated with image-guided HyRT presented a lower rate of grade 1-2 gastrointestinal toxicity (25.3% vs. 42.2%, p=0.001). At the last follow-up, the grade 1 Gastro-intestinal toxicity rate was 4.0% and the grade 1-2 genito-urinary toxicity rate was 25.1%. Our study demonstrated the efficacy of the schedule used with a low rate of acute and late toxicities. Therefore, reduction of margins with image-guided HyRT is safe.

Oligometastases in prostate cancer

BackgroundProstate-specific membrane antigen positron emission tomography/computed tomography (PSMAPET/CT) is a new and evolving diagnostic method in prostate cancer with special impact on treatment planning in image-guided radiotherapy (IGRT). Initial results of metabolic response in repeated PSMA PET/CTs after hypofractionated IGRT for metastatic lesions are reported here.Materials and methodsOf 280 patients investigated with 68Ga-PSMA PET/CT in the period from 01/2014 through 12/2016 in the authors’ department, patients were selected according to the following criteria: oligometastatic disease at initial PSMA PET/CT defined as not more than five metastatic lesions, hypofractionated IGRT to all lesions, no systemic therapy in the last 6 months and during follow-up, and at least one follow-up PSMA PET after radiotherapy. Radiotherapy was administered to all PSMA PET-detected lesions (CTV = PET-GTV + 1 to 2 mm), mostly with 35 Gy in five fractions (one lesion with four fractions of 7 Gy due to dose constraints, two lymph nodes with 50 Gy in 25 fractions to an extended volume plus a boost of 7 Gy × 2 to the PET-positive volume). Metabolic response of irradiated lesions was evaluated on repeated PSMA PET/CTs according to PERCIST criteria. Five patients with a total number of 12 PSMA PETs matched the criteria. Patients received radiotherapy to all PET-positive lesions and had at least one (in one case three) follow-up PSMA PET examinations after radiotherapy with an interval to the first PET of 2–15 months; the median follow-up for all patients was 11 months.ResultsThe mean prostate-specific antigen (PSA) values at the time of examination were 8.9 ± 8.5 ng/ml (median 3.3 ng/ml, range 0.17–21.8 ng/ml). A total number of 18 metastatic deposits were detected. The PET-positive tumor volume was 5.9 ± 13.3 cm3 (median 1.25 cm3). The mean standardized uptake value (mean SUVmax) of the 18 metastatic lesions decreased from 19.9 ± 23.3 (mean ± SD) prior to RT to 5.4 ± 4.6 at post-radiotherapy PSMA PET/CT. Using PERCIST criteria, 14 lesions (78%) showed a metabolic response in PSMA PET with a reduction of SUV of at least 30%, as well as a significant decrease in lesion size; in seven of these lesions, no uptake of 68Ga-PSMA was detectable. In follow-up PET scans, only two lesions showed metabolic progression with an increase in SUVmax yielding a local progression-free survival of 88% after 1 year. There was a correlation between the time interval after radiotherapy (median 3 months, range 1–9 months) and response (p = 0.04) with better metabolic response after longer follow-up.ConclusionsPreliminary results of this study show high metabolic response rates of PSMA PET-positive metastatic lesions after hypofractionated radiotherapy in follow-up PSMA PET with promising local control rates. An interval of several months may be required to fully estimate the efficacy of radiotherapy in control PSMA PET.

Moderate hypofractionated image-guided thoracic radiotherapy for locally advanced node-positive non-small cell lung cancer patients with very limited lung function: a case report.

Patients with locally advanced lung cancer and very limited pulmonary function (forced expiratory volume in 1 second [FEV1] ≤ 1 L) have dismal prognosis and undergo palliative treatment or best supportive care. We describe two cases of locally advanced node-positive non-small cell lung cancer (NSCLC) patients with very limited lung function treated with induction chemotherapy and moderate hypofractionated image-guided radiotherapy (Hypo-IGRT). Hypo-IGRT was delivered to a total dose of 45 Gy to the primary tumor and involved lymph nodes. Planning was based on positron emission tomography-computed tomography (PET/ CT) and four-dimensional computed tomography (4D-CT). Internal target volume (ITV) was defined as the overlap of gross tumor volume delineated on 10 phases of 4D-CT. ITV to planning target volume margin was 5 mm in all directions. Both patients showed good clinical and radiological response. No relevant toxicity was documented. Hypo-IGRT is feasible treatment option in locally advanced node-positive NSCLC patients with very limited lung function (FEV1 ≤ 1 L).

Hypofractionated radiation therapy in low-risk prostate cancer: Outcome, toxicity, and sexual function.

e16575 Background: To evaluate efficacy, toxicity of image-guided hypofractionated radiotherapy (HFRT) in patients with low-risk prostate cancer. Methods: Eighty-five low-risk prostate cancer patients (Gleason score ≤6, clinical stage T1/T2a-b N0 M0, and PSA ≤10 ng/mL) were treated with HFRT from March 2007 to November 2015. All patients were staged with multi-parametric contrast-enhanced MRI. Clinical target volume (CTV) encompassed prostate with proximal seminal vescicles. Margin from CTV to PTV was 5 mm in all directions. Patients received a total dose of 60 Gy in 20 fractions with 3D-CRT. Daily cone beam CT (IGRT) was executed. RTOG/EORTC morbidity Scoring Scale was used for evaluate toxicities. Results: Median follow-up was 54 months (range 11-116 months). The actuarial 8-years Overall Survival was 97.1%. Eight-years Cancer Specific Survival was 100%, 8-years Biochemical Relapse Free Survival was 98.8%, no patients presented clinical local recurrence. Median of PSA at diagnosis was 3.27 ng/mL (range 1.69-9.98 ng/mL) and at the last follow-up was 0.39 ng/mL (range 0.01-2.26 ng/mL). Acute grade 1-2 gastrointestinal (GI) toxicity occurred in 13 patients (15.3%), grade 1-2 genitourinary (GU) toxicity in 33 cases (38.8%). Grade 3 GU toxicity occurred in 2 patients (2.4%). Grade 1-2 GI and GU late toxicities were observed in 4 (4.7 %) and 25 (29.4 %) patients, respectively. Sexual functionality was qualitatively evaluated, scoring 0 for absence, 1 for presence of erection but insufficient for intercourse, 2 for a sufficient one. Before RT, 4.7 % had score 0, 47.1% had score 1 and 48.2% had score 2. After RT, 34.1% of patients presented score 0, 51.8% score 1 and 14.1% score 2 (Chi-square p = 0,004). After treatment, patients with &lt; 70 years presented score 0 in 4.7% of patients, score 1 in 20% and score 2 in 8.2%. Those with &gt; 70 years, 29.4% presented score 0, 31.8% score 1 and 5.9% score 2 (Chi square p = 0.011). Conclusions: Long-term results of our study demonstrated that HFRT in low-risk prostate cancer is efficacy and well tolerated. HFRT significantly worsened sexual function, even if patients with age &lt; 70 years had a higher probability to maintain any form of sexual function after therapy.

PO-0694: Post-operative Intensity-Modulated hypofractionated Image-Guided Radiotherapy in cholangiocarcinoma

PO-0694: Post-operative Intensity-Modulated hypofractionated Image-Guided Radiotherapy in cholangiocarcinoma

Biological Benefits of Hypofractionated Image Guided Radiation Therapy in Postoperative Oligorecurrence of Thoracic Esophageal Cancer

Biological Benefits of Hypofractionated Image Guided Radiation Therapy in Postoperative Oligorecurrence of Thoracic Esophageal Cancer

Hypofractionated image guided radiation therapy followed by prostate seed implant boost for men with newly diagnosed intermediate and high risk adenocarcinoma of the prostate: Preliminary results of a phase 2 prospective study

PurposeA phase 2 protocol was designed and implemented to assess the toxicity and efficacy of hypofractionated image guided intensity modulated radiation therapy (IG-IMRT) combined with low-dose rate 103Pd prostate seed implant for treatment of localized intermediate- and high-risk adenocarcinoma of the prostate. Methods and materialsThis is a report of an interim analysis on 24 patients enrolled on an institutional review board–approved phase 2 single-institution study of patients with intermediate- and high-risk adenocarcinoma of the prostate. The median pretreatment prostate-specific antigen level was 8.15 ng/mL. The median Gleason score was 4 + 3 = 7 (range, 3 + 4 = 7 - 4 + 4 = 8), and the median T stage was T2a. Of the 24 patients, 4 (17%) were high-risk patients as defined by the National Comprehensive Cancer Network criteria, version 2016. The treatment consisted of 2465 cGy in 493 cGy/fraction of IG-IMRT to the prostate and seminal vesicles. This was followed by a 103Pd transperineal prostate implant boost (prescribed dose to 90% of the prostate volume of 100 Gy) using intraoperative planning. Five patients received neoadjuvant, concurrent, and adjuvant androgen deprivation therapy. ResultsThe median follow-up was 18 months (range, 1-42 months). The median nadir prostate-specific antigen was 0.5 ng/mL and time to nadir was 16 months. There was 1 biochemical failure associated with distant metastatic disease without local failure. Toxicity (acute or late) higher than grade 3 was not observed. There was a single instance of late grade 3 genitourinary toxicity secondary to hematuria 2 years and 7 months after radiation treatment. There were no other grade 3 gastrointestinal or genitourinary toxicities. ConclusionsEarly results on the toxicity and efficacy of the combination of hypofractionated IG-IMRT and low-dose-rate brachytherapy boost are favorable. Longer follow-up is needed to confirm safety and effectiveness.