Hypofractionated External Beam Radiotherapy Research Articles

Second Malignancy Probabilities in Patients With Breast Cancer Treated With Conventional Versus Hypofractionated External Beam Radiation Therapy in the Adjuvant Setting

AimsFor women with breast cancer, seminal studies have shown that adjuvant hypofractionated external beam radiation therapy (hEBRT) maintains similar outcomes and may reduce overall costs compared with conventionally fractionated external beam radiation therapy (cEBRT). However, it is unclear whether hEBRT may be associated with differential risk of development of radiation-induced second malignancies compared with cEBRT. Because the occurrence of second malignancies is small, large databases may improve our understanding of the relative risk of second malignancies between hEBRT and cEBRT. Materials and methodsUsing the National Cancer Database, we carried out a retrospective cohort analysis of women diagnosed with non-metastatic, stage 0–III breast cancer from 2004 to 2017. All patients had a lumpectomy or mastectomy and a follow-up time of at least 60 months after diagnosis. The probability of second malignancies in women receiving adjuvant cEBRT or hEBRT was compared using multivariable logistic regression adjusting for sociodemographic, geographical, clinical and treatment factors, allowing for relative (but not absolute) comparison of second malignancy risk. Temporal sensitivity analyses stratified by year of diagnosis and length of follow-up time were also conducted. ResultsOf the 125 228 women in our study, 115 576 (92.3%) received cEBRT and 9652 (7.71%) received hEBRT. The median age of the cohort was 60 (interquartile range 51–68) years at diagnosis and the median follow-up time was 99.61 (interquartile range 77.5–128.49) months. Upon adjusting for sociodemographic and clinical factors, patients who received hEBRT had no difference in relative risk than patients who received cEBRT (odds ratio 0.937, 95% confidence interval 0.869–1.010, P = 0.091). In analyses stratified by year of diagnosis, and stratified by length of follow-up, there was no difference in second malignancy probability between patients who completed hEBRT and patients who completed cEBRT. ConclusionsIn this analysis of over 120 000 women with non-metastatic breast cancer, hEBRT was not associated with different odds of developing second malignancies compared with cEBRT. Our findings may inform patient counselling in the choice of radiation regimens for breast cancer and further support the safety of hypofractionated regimens for breast cancer.

Low-dose-rate brachytherapy in low-risk prostate cancer- treatment results, radiation toxicity and quality of life-dissertation project with literature review

Low-dose-rate brachytherapy (LDR-BT) is a an internal radiation therapy method for the treatment of localized prostate cancer The treatment modality has been known for several decades. The choice of the treatment modality for prostate cancer patients depends mainly on the stage of the disease and the prognostic factors. Brachytherapy monotherapy is a well-tolerated procedure compared to alternative treatments. Based on a literature review, we have considered a prospective study on the treatment efficiency after LDR-BT with a permanent iodine-125 (I-125) implant, compared to that of hypo-fractionated external beam radiotherapy (EBRT) alone. The working thesis is to present the advantages and disadvantages of LDR-BT for low-risk prostate carcinoma, compared to a similar group of patients treated with definitive intensity-modulated hypo-fractionated radiotherapy (IMHRT)

Long-term oncologic outcomes of low dose-rate brachytherapy compared to hypofractionated external beam radiotherapy for intermediate -risk prostate cancer

PURPOSETo compare the long-term oncologic outcomes of intermediate risk (IR) prostate cancer (PCa) patients treated with low dose-rate brachytherapy (LDR-BT) or moderate hypofractionated external beam radiotherapy (HF-EBRT). METHODS AND MATERIALSPatients diagnosed with IR PCa and treated with LDR-BT or HF-EBRT between January 2005 and December 2013 were included. Brachytherapy treatment involved a transperineal implant of iodine-125 to a dose of 145 Gy to the PTV, while HF-EBRT was delivered using intensity modulated radiotherapy with 60 Gy in 20 fractions. The Phoenix ‘‘nadir +2’’ threshold was used to define biochemical relapse (BR). The cumulative incidence function (CIF) of BR and metastases was reported for each group and compared using the Gray's test to account for the competing risk of death. The Kaplan-Meier (KM) method was used to estimate overall survival (OS) and prostate cancer specific survival (PCSS). Univariate (UVA) and multivariable (MVA) analysis of the CIF of BR and metastases were performed. A 2-tailed p-value ≤ 0.05 was considered statistically significant. RESULTSOverall, 122 and 124 patients were treated with LDR-BT and HF-EBRT respectively. Median follow-up was 95 months [interquartile range (IQR): 79–118] in the LDR-BT group and 96 months (IQR: 63–123) in the HF-EBRT group. BR was observed in 5 patients treated with LDR-BT and 34 treated with HF-EBRT. At 60 and 90 months, the CIF of BR was 0.9% and 3.5% in the LDR-BT group vs. 16.6% and 23.7% in the HF-EBRT (p < 0.001). The CIF of metastases at 90 and 108 months, was 0% and 1.6% vs. 3.4% and 9.1% in the LDR-BT and HF-EBRT groups (p = 0.003), respectively. At the last follow-up, 3 patients treated with HF-EBRT died from their cancer [PCSS of 97.5% at 8 years and none died in the LDR-BT group (p = 0.09). On UVA and MVA risk group and treatment modality were independently associated with CIF of BR. On UVA HF-EBRT and ISUP grade group 3 were associated with metastases. CONCLUSIONLDR-BT was associated with higher biochemical and metastases control in our cohort when compared to moderately HF-EBRT. In the absence of a randomized trial, LDR-BT when feasible should be offered to patients with a life expectancy of >8 years.

Phase II Study of ENZAlutamide Combined With Hypofractionated Radiation Therapy (ENZART) for Localized Intermediate Risk Prostate Cancer.

BackgroundIntermediate-risk prostate cancer (PCa) is usually treated by a combination of external beam radiation therapy (EBRT) and a short course of androgen deprivation therapy (ADT). ADT is associated with multiple side effects, including weight gain, loss of libido, and hot flashes. In contrast, anti-androgen monotherapy is generally better tolerated in spite of higher rates of gynecomastia.ObjectiveThis study assessed the effectiveness of enzalutamide monotherapy combined with hypofractionated EBRT (Hypo-EBRT) for treating intermediate risk prostate cancer.MethodThis trial was a multicenter, open-label phase II study of 6 months of enzalutamide monotherapy combined with Hypo-EBRT for intermediate-risk prostate cancer. Hypo-EBRT was initiated 8–12 weeks after initiating enzalutamide. The primary endpoint was PSA decline >80% measured at the 25th week of enzalutamide administration. Secondary end-points included assessment of toxicity, changes in anthropomorphic body measurements, sexual hormones, and metabolic changes.ResultsSixty-two patients were included in the study from January 2018 to February 2020. A PSA decline of >80% was observed in all evaluable patients at the end of enzalutamide treatment and 92% achieved PSA values under 0.1 ngr/ml. All patients remain in PSA response (<80% reduction of the initial values) 6 months after the end of enzalutamide treatment. The most frequent adverse events were hypertension, asthenia, and gynecomastia. There were no significant changes in bone density, body mass index (BMI), or patient-reported outcomes (PROs).ConclusionEnzalutamide monotherapy is very effective along with hEBRT in reducing PSA levels for patients with intermediate-risk prostate cancer. Longer follow-up is needed to confirm the potential use of this combination in future randomized trials.

A phase IB clinical trial of 15 Gy HDR brachytherapy followed by hypofractionated/SBRT in the management of intermediate-risk prostate cancer

PurposeHigh dose-rate (HDR) brachytherapy is commonly administered as a boost to external beam radiation therapy (EBRT). Our purpose was to compare toxicity with increasingly hypofractionated EBRT in combination with a single 15 Gy HDR boost for men with intermediate-risk prostate cancer. Methods and MaterialsForty-two men were enrolled on this phase IB clinical trial to one of three EBRT dose cohorts: 10 fractions, seven fractions, or five fractions. Patients were followed prospectively for safety, efficacy, and health-related quality of life (Expanded Prostate Index Composite). Efficacy was assessed biochemically using the Phoenix definition. ResultsWith a median follow up of 36 months, the biochemical disease-free survival was 95.5%. One man developed metastatic disease at 5 years. There was no significant minimally important difference in EPIC PRO for either urinary, bowel, or sexual domains. There was one acute Grade 3 GI and GU toxicity, but no late Grade 3 GU or GI toxicities. ConclusionFifteen gray HDR brachytherapy followed by a five fraction SBRT approach results in high disease control rates and low toxicity similar to previously reported HDR protocols with significant improvement in patient convenience and resource savings. While mature results with longer follow up are awaited, this treatment approach may be considered a safe and effective option for men with intermediate-risk disease.

Acute Palliation of Intrathoracic Symptoms: No Improvement with Dose-Escalated Hypofractionated External Beam Radiotherapy

Primary or metastatic malignant disease is a known cause of intrathoracic symptoms in oncologic patients and, frequently, obstruction of the bronchial tree may lead to dyspnea and/or hemoptysis. Local external beam radiotherapy (EBRT) can be an option to palliate such symptoms, even in spite of its low efficiency rate. We hypothesized that dose escalation could be safely delivered and further improve symptoms relief rates in patients who did not respond to an initial course of hypofractionated EBRT. A prospective, single arm, uni-institutional study was conducted, and eligible patients were offered a course of local hypofractionated EBRT, with 2 weekly fractions of 8 Gy, and an additional fraction of 8 Gy, if there were no symptoms improvement, one week apart. Study primary endpoint was to assess the rate of acute palliation of intrathoracic symptoms (hemoptysis resolution and/or dyspnea improvement, measured by the Modified Medical Research Council [mMRC] Dyspnea Scale). Secondary endpoints included the assessment of any possible treatment side-effects and late symptom improvement. Patients were clinically evaluated before every EBRT session, and if there was no clinical improvement after the second and immediately before the third session, the patient was recommend to continue the proposed treatment, to a total dose of 24 Gy. After that, follow-up was performed on a regular basis, to evaluate any possible treatment sub-acute or late side-effects or symptom improvement. After ERB approval, on September 2017, 8 eligible patients (5 males and 3 females) were initially enrolled, until interim analyses, on August 2018, when investigators decided to close accrual due to poor response to the treatment protocol. Median age of the patients was 51,5 years (39 - 72), all of them with metastatic disease and 5 of them (62,5 %) with a non-pulmonary primary malignancy. All of the patients presented with dyspnea, and 2 (25 %) of them also with hemoptysis, and, according to mMRC Dyspnea Scale, 6 patients (75 %) had a grade 3 or higher dyspnea symptom. Overall, 5 of the patients demanded a third session, but one patient died from disease progression before the second and one before the third session. After the completion of the treatment protocol, 4 patients had any acute dyspnea improvement and both the patients who presented with hemoptysis had symptom resolution (one after the second session, and therefore was not submitted to the third one). However, none evolved with significant dyspnea palliation after the third session. Except for one patient, that was still alive 12 months after the EBRT, all the other patients died within 4 months after the completion of the treatment. Two out of 3 patients who completed the 3 sessions also developed symptomatic actinic esophagitis. Dose-escalated hypofractionated EBRT didn’t provide acute palliation of intrathoracic symptoms in this small cohort of patients, despite any dyspnea improvement in 5 out of 8 patients.

Twice- vs. thrice-weekly moderate hypofractionated radiotherapy for prostate cancer: does overall treatment time matter?

To evaluate the influence of overall treatment time (OTT) in disease control, acute, and long-term side effects with moderate hypofractionated external beam radiotherapy (RT) for prostate cancer (PCa) delivered either twice- or thrice-a-week. 157 patients with localized PCa were treated consecutively with 56Gy in 4Gy/fraction delivered either twice (86 patients, from 2003 to 2010, group-1) or thrice a week (71 patients, from 2010 to 2017, group-2) using IMRT or VMAT techniques. Gastrointestinal (GI) and genitourinary (GU) toxicities were scored according to the CTCAE v3.0 grading scale. Median follow-up was 110 and 56months for groups 1 and 2, respectively. At 6weeks, patients treated thrice-a-week experienced higher acute ≥ grade-2 GU toxicity compared to those treated twice a week (25.4% vs 5.8%, p = 0.001) even though none presented ≥ grade-3 GU or GI toxicity in the thrice-a-week group. The 5-year ≥ grade-2 late GU toxicity-free survival was higher in group-1 (95.9 ± 2.3%) than in group-2 (81.5 ± 4.9%, p = 0.003), while no differences in ≥ grade-2 late GI toxicity-free survival were observed between both groups (97.5 ± 1.7% vs. 97 ± 2.1% for groups 1 and 2, respectively). The 5-year biochemical relapse-free survival (bRFS) was not different for patients treated twice compared to those treated thrice-a-week (80.6 ± 4.5% vs. 85.3 ± 4.8%, respectively, p = 0.441), as much as for patients treated in > 5weeks vs. those treated in ≤ 5weeks (81.3 ± 4.4% vs. 84.4 ± 5.1%, respectively, p = 0.584). In this retrospective hypothesis-generating analysis, less vs. more than 5weeks OTT may increase acute and late GU toxicities without significantly improving bRFS in patients treated to high effective doses (> 80Gy) with moderate hypofractionated RT. Prospective trials evaluating the impact of OTT on hypofractionated schedules for PCa are warranted.

A pilot study of patient reported outcomes evaluating treatment related symptoms and quality of life for men receiving high dose rate brachytherapy combined with hypo-fractionated radiotherapy or hypo-fractionated radiotherapy alone for the treatment of localised prostate cancer.

Patient Reported Outcome Measures (PROMS) are useful metrics in evidence-based clinical care and translational research. Recording treatment-related symptoms and Quality of Life (QoL) can provide information in counselling patients to aid decision-making. This prospective study tested the feasibility of radiographer-led collection of multiple validated PROMS from Prostate Cancer (PCa) patients comparing High Dose Rate Brachytherapy combined with hypo-fractionated external beam radiotherapy (hEBRT) and hEBRT alone. From June to August 2017, 20 men with localised PCa (T1-T3aN0M0) consented to participate in the study. Ten patients received combination treatment (37.5 Gray/15 fractions followed by a 15 Gray implant), and ten patients received monotherapy (60 Gray/20 fractions). PROMS were collected at four time-points (1) at baseline, (2) final fraction of hEBRT, (3) 8 weeks after commencing radiotherapy and (4) 12 weeks after commencing radiotherapy. The PROMS used were EPIC-26, IPSS, IIEFF-5 and SF-12. The difference between the two groups were tested using Mann-Whitney U test and Wilcoxon Signed-Rank Test. All participants completed all PROMS (100% response-rate). The Monotherapy group reported a higher incidence of bowel symptoms compared to the combination group and at Week 12, EPIC-26 bowel summary score demonstrated a statistically significant difference (p = 0.005). The prevalence of erectile dysfunction increased within both groups. Maintenance of QoL was reported throughout treatment. This small study demonstrated feasibility of radiographer-led PROMS collection by 100% completion rate. Streamlining of these tools into integrated technology applications and real time PROMS measurement has the ability to benefit patients and guide clinicians in adapting therapies based on individual need.

Glioblastoma multiforme (GBM) in the elderly: initial treatment strategy and overall survival.

The EORTC trial which solidified the role of external beam radiotherapy (EBRT) plus temozolomide (TMZ) in the management of GBM excluded patients over age 70. Randomized studies of elderly patients showed that hypofractionated EBRT (HFRT) alone or TMZ alone was at least equivalent to conventionally fractionated EBRT (CFRT) alone. We sought to investigate the practice patterns and survival in elderly patients with GBM. We identified patients age 65-90 in the National Cancer Data Base (NCDB) with histologically confirmed GBM from 1998 to 2012 and known chemotherapy and radiotherapy status. We analyzed factors predicting treatment with EBRT alone vs. EBRT plus concurrent single-agent chemotherapy (CRT) using multivariable logistic regression. Similarly, within the EBRT alone cohort we compared CFRT (54-65Gy at 1.7-2.1Gy/fraction) to HFRT (34-60Gy at 2.5-5Gy/fraction). Multivariable Cox proportional hazards model (MVA) with propensity score adjustment was used to compare survival. A total of 38,862 patients were included. Initial treatments for 1998 versus 2012 were: EBRT alone = 50 versus 10%; CRT = 6 versus 50%; chemo alone = 1.6% (70% single-agent) versus 3.2% (94% single-agent). Among EBRT alone patients, use of HFRT (compared to CFRT) increased from 13 to 41%. Numerous factors predictive for utilization of CRT over EBRT alone and for HFRT over CFRT were identified. Median survival and 1-year overall survival were higher in the CRT versus EBRT alone group at 8.6 months vs. 5.1 months and 36.0 versus 15.7% (p < 0.0005 by log-rank, multivariable HR 0.65 [95% CI = 0.61-0.68, p < 0.0005], multivariable HR with propensity adjustment 0.66 [95% CI = 0.63-0.70, p < 0.0005]). For elderly GBM patients in the United States, CRT is the most common initial treatment and appears to offer a survival advantage over EBRT alone. Adoption of hypofractionation has increased over time but continues to be low.

Long-term Toxicity and Health-related Quality of Life after Single-fraction High Dose Rate Brachytherapy Boost and Hypofractionated External Beam Radiotherapy for Intermediate-risk Prostate Cancer

AimsTo report health-related quality of life (HRQOL) and toxicity in prostate cancer patients treated with single-fraction high dose rate (HDR) brachytherapy boost and external beam radiotherapy (EBRT). Materials and methodsPatients with intermediate-risk prostate cancer were accrued to a phase II clinical trial of 15 Gy HDR boost and EBRT to a dose of 37.5 Gy in 15 fractions. HRQOL (Expanded Prostate Cancer Index Composite [EPIC]), urinary symptoms (International Prostate Symptom Score [IPSS]), erectile function (International Index of Erectile Function [IIEF]) and toxicity (Common Terminology Criteria for Adverse Events [CTCAE], version 3.0) were monitored prospectively. Univariate and multivariate logistic regression analysis was used to investigate associations between HRQOL/toxicity and baseline covariates. ResultsThe median follow-up time was 5.2 years. The change in the median EPIC scores from baseline to year 5 in the urinary domain was from 91 to 85 (P = 0.0028), in the bowel domain was from 98 to 96 (P = 0.03), in the sexual domain was from 63 to 35 (P < 0.0001) and the hormonal domain remained unchanged at 95 (P = 0.93). Fifty-nine per cent and 46% of the patients with normal erectile function at baseline remained potent at year 1 and year 5, respectively. Late genitourinary toxicity grade 1, 2 and ≥3 occurred in 29, 59 and 4% of patients, respectively. The rates of late gastrointestinal toxicity grade 1, 2 and ≥3 were documented as 45, 19 and 0%, respectively. On multivariate logistic regression analysis, patients with larger prostates were more likely to develop a urinary late toxicity grade ≥2 (P = 0.01). The dose to 10% of the urethra was the only factor associated with a decline in the EPIC urinary domain score (P = 0.012). Prostate volume >43 ml was associated with higher late genitourinary toxicity grade ≥2. ConclusionsSingle 15 Gy HDR brachytherapy with EBRT has a low rate of late genitourinary and gastrointestinal toxicities. Late urinary morbidity may be minimised by limiting the dose to the urethra, particularly for patients with larger prostates.

Technique of Injection of Hyaluronic Acid as a Prostatic Spacer and Fiducials Before Hypofractionated External Beam Radiotherapy for Prostate Cancer

To describe a technique combining the implantation of fiducials and a prostatic spacer (hyaluronic acid [HA]) to decrease the rectal toxicity after an image-guided external beam radiotherapy (EBRT) with hypofractionation for prostate cancer and to assess the tolerance and the learning curve of the procedure. Thirty patients with prostate cancer at low or intermediate risk were included in a phase II trial: image-guided EBRT of 62 Gy in 20 fractions of 3.1 Gy with intensity-modulated radiotherapy. A transrectal implantation of 3 fiducials and transperineal injection of 10 cc of HA (NASHA gel spacer, Q-Med AB, Uppsala, Sweden) between the rectum and the prostate was performed by 1 operator. The thickness of HA was measured at 10 points on magnetic resonance imaging to establish a quality score of the injection (maximum score = 10) and determine the learning curve of the procedure. The quality score increased from patients 1-10, 11-20, to 21-30 with respective median scores: 7 [2-10], 5 [4-7], and 8 [3-10]. The average thicknesses of HA between the base, middle part, and apex of the prostate and the rectum were the following: 15.1 mm [6.4-29], 9.8 mm [5-21.2], and 9.9 mm [3.2-21.5]. The injection of the HA induced a median pain score of 4 [1-8] and no residual pain at mid-long term. Creating an interface between the rectum and the prostate and the implantation of fiducials were feasible under local anesthesia with a short learning curve and could become a standard procedure before a hypofractionated EBRT for prostate cancer.

Glioblastoma Multiforme (GBM) in the Elderly: Initial Treatment Strategy and Overall Survival

The EORTC trial which solidified the role of external beam radiotherapy (EBRT) plus temozolomide (TMZ) in the management of GBM excluded patients over age 70. Randomized studies of elderly patients showed that hypofractionated EBRT (HFRT) alone or TMZ alone was at least equivalent to conventionally fractionated EBRT (CFRT) alone. We sought to investigate the practice patterns and survival in elderly patients with GBM. We identified patients age 65–90 in the National Cancer Data Base (NCDB) with histologically confirmed GBM from 1998 to 2012 and known chemotherapy and radiotherapy status. We analyzed factors predicting treatment with EBRT alone vs. EBRT plus concurrent single-agent chemotherapy (CRT) using multivariable logistic regression. Similarly, within the EBRT alone cohort we compared CFRT (54–65 Gy at 1.7–2.1 Gy/fraction) to HFRT (34–60 Gy at 2.5-5 Gy/fraction). Multivariable Cox proportional hazards model (MVA) with propensity score adjustment was used to compare survival. A total of 38,862 patients were included. Initial treatments for 1998 versus 2012 were: EBRT alone = 50 versus 10%; CRT = 6 versus 50%; chemo alone = 1.6% (70% single-agent) versus 3.2% (94% single-agent). Among EBRT alone patients, use of HFRT (compared to CFRT) increased from 13 to 41%. Numerous factors predictive for utilization of CRT over EBRT alone and for HFRT over CFRT were identified. Median survival and 1-year overall survival were higher in the CRT versus EBRT alone group at 8.6 months vs. 5.1 months and 36.0 versus 15.7% (p < 0.0005 by log-rank, multivariable HR 0.65 [95% CI = 0.61–0.68, p < 0.0005], multivariable HR with propensity adjustment 0.66 [95% CI = 0.63–0.70, p < 0.0005]). For elderly GBM patients in the United States, CRT is the most common initial treatment and appears to offer a survival advantage over EBRT alone. Adoption of hypofractionation has increased over time but continues to be low.

A Study on Dosimetric Outcomes and Acute Toxicity of Post Mastectomy Adjuvant Hypofractionated Radiotherapy for Breast Cancer.

Hypofractionated External Beam Radiotherapy (HFRT) is a relatively new adjuvant Radiotherapy (RT) schedule for breast cancers following breast conservation surgery and less commonly, following mastectomy. Here we report our experience on normal tissue exposure and acute toxicity of HFRT after mastectomy. To assess the dosimetric outcomes and acute toxicity profile of adjuvant HFRT following mastectomy for breast cancer. This prospective observational study considered consecutive patients planned for adjuvant HFRT (42.5 Gy in 16 sessions delivered over 3 weeks) to the chest wall with/without regional nodes between October 2014 and June 2015. The dosimetric parameters including dose homogeneity to the target volume and exposure to heart and lung were analyzed. Acute haematological and dermatological toxicity was recorded until upto three months after completion of RT. Among the 56 patients treated with HFRT, the mean age was 49 years (range: 28-69 years). Pathologically positive nodes and ≥pT3 primary was observed in 44 (78.6%) and 12 (21.4%) patients, respectively. Majority (87.5%) received prior adjunct chemotherapy. RT to the supraclavicular fossa was delivered for 39 (69.6%) patients. The mean V90 and V95 to the Planning Target Volume (PTV) were 95% (± 3.3%) and 93% (± 4%), respectively. The maximum dose received was on average 47.7 Gy (112%; range: 46.2-48.5 Gy). The mean lung dose was 10.2 Gy (± 3.5 Gy) and V20 was 20.9% (± 6%). The mean V25 to heart was 6.6% (± 4.8%) for left sided and 0% for right sided tumours (p=0.001). Acute skin toxicity peaked at completion of RT and was tolerable (grade 0, I, II and III reactions were 75%, 16% and 1.8%, respectively). No patient had ≥ grade III haematological toxicity, and treatment was not interrupted for any patient. Adjuvant HFRT could be planned while meeting the dose constraints to normal tissues in all patients and was well tolerated, with mild to moderate acute adverse effects that did not warrant any therapeutic intervention or treatment interruption.

Salvage high-dose-rate brachytherapy for histologically confirmed macroscopic local relapsed prostate cancer after radical prostatectomy.

PurposeTo evaluate the feasibility of the use of real-time magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) fusion guided high-dose-rate brachytherapy (HDR-BT) +/– external beam radiation therapy (EBRT) in patients with histologically-proven local relapse after radical prostatectomy.Material and methodsWe retrospectively reviewed 13 patients treated with real-time MRI-TRUS fusion HDR-BT for a local relapse of prostate cancer after radical surgery. All patients underwent multiparametric magnetic resonance imaging (mpMRI) to confirm the presence of macroscopic lesions in prostate bed, and choline positron emission tomography/computed tomography (PET/CT) to rule out nodal or distant metastases. Local failure was confirmed by transrectal biopsy. Patients without previous EBRT received 1 fraction of 15 Gy with HDR-BT plus hypofractionated EBRT (37.5 Gy in 15 fractions). Two patients received 2 fractions of 12 Gy with HDR-BT without EBRT. Follow-up visits were at 1, 3, 6 months, and every 6 months thereafter.ResultsAfter a median follow-up of 7 months, all patients showed an appropriate biochemical response. Median prostate-specific antigen (PSA) levels before treatment, 1 month, and 6 months after HDR-BT were 2.62 ng/ml (range: 1.55-9.61), 0.97 ng/ml (range: 0.12-3.14), 0.23 ng/ml (range: 0.1-0.74), respectively. Five patients (42%) experienced acute grade 1 GU toxicity and 1 patient (8%) suffered from grade 2 GU toxicity. Regarding gastrointestinal (GI) toxicity, 5 patients referred grade 1 acute toxicity and 1 grade 2 (proctitis). No late toxicity has been observed so far.ConclusionsMRI-TRUS fusion guided salvage HDR-BT +/– EBRT is a feasible procedure for patients with local macroscopic relapse in tumor bed after radical prostatectomy. Exquisite selection of patients through mpMRI and choline PET/CT is crucial to avoid overtreatment. A larger number of patients and longer follow-up are required in order to draw more solid conclusions regarding the effectiveness of this strategy.

Methodological aspects of extreme hypofractionated external beam radiotherapy for prostate cancer with target volume immobilization by an endorectal balloon

Methodological aspects of extreme hypofractionated external beam radiotherapy for prostate cancer with target volume immobilization by an endorectal balloon

Abstract P1-15-05: Long-term outcome of electron intraoperative boost and hypofractionated external beam radiotherapy after breast-conserving surgery in premenopausal women

Abstract Purpose: To report long-term clinical results on breast cancer patients treated with a electron intraoperative boost followed by hypofractionated external beam radiotherapy (HEBRT) to the whole breast inside a clinical protocol. Materials and Methods: Between June 2004 and December 2008, 357 premenopausal women with a diagnosis of early-stage breast cancer were given breast conservative surgery (quadrantectomy and sentinel node biopsy +\- axillary dissection). During surgery, an electron intraoperative boost of 12 Gy was administered to the tumour bed. Within 4 weeks after having received the IORT boost, the whole breast was irradiated with hypofractionated scheme. HEBRT consisted of 13 daily fractions of 2.85 Gy up to a total dose of 37.05 Gy, with 3-D conformal technique. Median age was 42 years (24-48). Pathologic stages were distributed as follow: stage 0 4 (1.1%), I 192(53.8%), stage IIA 108 (30.3%), stage IIB 28 (7.8%), stage IIIA 18 (5%), stage IIIC 6 (1.7%), CR 1(0.3 %). The biomolecular classification included 33 triple negative patients. All patients but one received adjuvant systemic treatment, according to tumor features. Chemotherapy +/- endocrinotherapy was offered to 149 patients, while endocrinotherapy alone was given to 197 patients. In all cases, adjuvant chemotherapy commenced after the completion of HEBRT. Follow-up was carried out on a regular basis by breast surgeons and radiation oncologists. Results: Median follow-up was 83.1 months (range 9.1-118.9). 340 patients were alive and 317 were free of any disease (89%). Three patients (0.8%) had nodal regional recurrence, 12 patients (3.4%) had local recurrence, 26 patients (7.3%) had distant metastasis.13 patients (3.6%) developed contralateral breast cancer.12 patients (3.4%) had a new primary tumor in other site. 15 patients (4.2%) died due to progression of disease, while two died of other causes not related to the breast cancer. Conclusions: This shortened scheme including intraoperative anticipated boost and hypofractionated whole breast radiotherapy showed a good local control at 5 years follow-up. The patients’ compliance is very high and in patients who are in need of chemotherapy, the time gap between surgery and radiotherapy treatment is avoided. As follow-up length increases, a greater number of patients will achieve the minimum 5 -year period to receive the first long-term evaluation and the strength of the results on efficacy is bound to increase. Citation Format: Maria Cristina Leonardi, Anna Morra, Cristiana Fodor, Luigi Santoro, Samantha Dicuonzo, Roberta Lazzari, Veronica Dell'acqua, Elena Rondi, Federica Cattani, Floriana Pansini, Alberto Luini, Roberto Orecchia. Long-term outcome of electron intraoperative boost and hypofractionated external beam radiotherapy after breast-conserving surgery in premenopausal women [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-05.

A comparative study of quality of life in patients with localized prostate cancer treated at a single institution: Stereotactic ablative radiotherapy or external beam + high dose rate brachytherapy boost

PurposeTo compare the quality of life (QOL) in patients treated with stereotactic ablative radiation therapy (SABR) alone or high dose rate (HDR) brachytherapy+hypofractionated external beam radiotherapy (EBRT). Methods and materialsPatient self-reported QOL was prospectively measured among patients from two sequential phase 2 clinical trials: 1-SABR 35Gy/5fractions/5weeks, 2–15Gy HDR 1 fraction, followed by EBRT 37.5Gy/15fractions/3weeks. The expanded prostate cancer index composite was assessed at baseline and q6 monthly up to 5years. Urinary, bowel and sexual domains were analyzed. A minimally clinical important change (MCIC) was defined as 0.5*standard deviation of the baseline for each domain. Fisher exact test and general linear mixed model were used (p<0.05). Results84 and 123 patients were treated on the SABR and HDR boost studies, with a median follow up of 51 and 61months respectively. There was a significant difference in MCIC between treatments in the urinary function and bother (p<0.0001), the bowel function (p=0.0216) and the sexual function (p=0.0419) and bother (p=0.0290) domains in favor of the SABR group. Of patients who reported no problem with their sexual function at baseline, 7% and 23% respectively considered it to be a moderate to big problem on follow up (p=0.0077). ConclusionPatients treated with HDR-boost reported deterioration of QOL particularly in sexual domains in comparison with SABR.

Low Acute Toxicity in Prostate Cancer Patients Treated With Hypofractionated External Beam Radiation Therapy and Single Fraction HDR Brachytherapy

To evaluate the acute genitourinary (GU) and gastrointestinal (GI) toxicity for a scheme of external beam radiation therapy (EBRT) and high dose rate brachytherapy (HDR-BT) for prostate cancer patients. Between January 2010 and June 2013, we treated 114 patients with high risk prostate cancer (T≥3a, limited T3b and/or Gleason score>7) at our radiation institute. All patients received neo-adjuvant hormonal therapy. The EBRT delivered 58 Gy in 20 fractions to prostate and seminal vesicles with a helical intensity modulated radiation therapy technique. A PTV margin of 7 mm was used, and at the overlap of the PTV and the rectum/bladder a dose gradient of 95% to 85% of the prescribed dose was applied. Two weeks afterwards a single fraction of 10 Gy HDR-BT to prostate and the base of the seminal vesicles was given with an integrated boost to the dominant intraprostatic tumor region aiming for a dose of 15 Gy. The full brachytherapy procedure was performed in the operating theatre, on an outpatient basis. The radiation oncologist scored GU and GI toxicity based on patient questionnaires and follow-up visits. NCI-CTCAE v3.0. was used as scoring system. One hundred and twelve patients had a minimal follow-up of 3 months and were evaluable for acute toxicity. Two patients were lost to follow up. The majority of patients (87.5%) reported no or mild GU toxicity (grade 0-1). Thirteen patients (11.6%) developed grade 2 toxicity. Patients reported mainly urge and high frequency complaints, 5 patients had a urinary retention requiring temporary catheterization (< 6 weeks). One grade 3 toxicity was reported. The patient (0.9%) needed a dilatation of the urinary tract because of stenosis. Ninety-seven patients (86.6%) showed no GI toxicity. Fifteen patients (13.4%) showed grade 1 toxicity. Mainly slight blood loss, change of consistency and mild pain. One patient reported anal incontinence for which occasional use of pads was required Grade 2,3 and 4 toxicity was not reported. Our hypofractionated EBRT and HDR-BT scheme for high risk prostate cancer patients is a save procedure with low acute toxicity.

A Comparative Study of Quality of Life in Patients with Localized Prostate Cancer Treated in a Single Institution: Stereotactic Radiotherapy or External Beam + High-Dose-Rate Brachytherapy Boost

Purpose: To compare the quality of life (QOL) in patients treated with stereotactic ablative radiation therapy (SABR) alone or high dose rate (HDR) brachytherapy + hypofractionated external beam radiotherapy

Change in prostate volume during extreme hypo-fractionation analysed with MRI

BackgroundHypo-fractionated external beam radiotherapy with narrow CTV-PTV margins is increasingly applied for prostate cancer. This demands a precise target definition and knowledge on target location and extension during treatment. It is unclear how increase in fraction size affects changes in prostate volume during treatment. Our aim was to study prostate volume changes during extreme hypo-fractionation (7 × 6.1 Gy) by using sequential MRIs.MethodsTwenty patients treated with extreme hypo-fractionation were recruited from an on-going prospective randomized phase III trial. An MRI scan was done before start of treatment, at mid treatment and at the end of radiotherapy. The prostate was delineated at each MRI and the volume and maximum extension in left-right, anterior-posterior and cranial-caudal directions were measured.ResultsThere was a significant increase in mean prostate volume (14%) at mid treatment as compared to baseline. The prostate volume remained enlarged (9%) at the end of radiotherapy. Prostate swelling was most pronounced in the anterior-posterior and cranial-caudal directions.ConclusionsExtreme hypo-fractionation induced a significant prostate swelling during treatment that was still present at the time of last treatment fraction. Our results indicate that prostate swelling is an important factor to take into account when applying treatment margins during short extreme hypo-fractionation, and that tight margins should be applied with caution.