Combined External Beam Radiotherapy Research Articles

A Multicenter Phase 2 study of Hypofractionated Stereostatic Boost in Intermediate Risk Prostate Carcinoma: A 5-Year Analysis of the CKNO-PRO Trial

The aim of this analysis was to assess the 5-year tolerance and survival in patients undergoing hypofractionated stereotactic boost after external beam radiation therapy (EBRT) for intermediate-risk prostate cancer. Between August 2010 and April 2013, 76 patients with intermediate-risk prostate carcinoma were included in the study. A first course delivered 46 Gy using conventional fractionation. The second course delivered a boost of 18 Gy (3 × 6 Gy) within 10 days using stereotactic body radiation therapy (SBRT). Gastrointestinal and genitourinary toxicities were assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events v4.0. Secondary outcome measures were overall, biochemical relapse-free, and relapse-free survival; prostate-specific antigen kinetics; and patient functional status (urinary and sexual) according to the International Index of Erectile Function and International Prostate Symptom Score questionnaires. Sixty patients (79%) were treated by CyberKnife and 16 (21%) by linear accelerator. Median follow-up was 62 months (range, 29-69). The cumulative incidence of genitourinary and gastrointestinal grade ≥2 toxicities at month 60 after the end of radiation therapy was 1.4% (95% confidence interval [CI], 0.1%-6.6%) and 9.3% (95% CI, 4.1%-17.1%), respectively. Biochemical relapse-free and relapse-free survival rates at 5 years were 87.4% (95% CI, 77.1%-93.2%) and 86.2% (95% CI, 75.8-92.3), respectively. The mean (standard deviation) prostate-specific antigen variation within 3 months and 5 years post-radiation therapy was -1.20 ng/mL/mo (0.79) and -1.30 ng/mL/y (1.05), respectively. There was no significant difference between the International Prostate Symptom quality of life score between inclusion and month 60. For the International Index of Erectile Function, there was a significant difference between inclusion and month 60 (P = .005), with a higher proportion of severe/noninterpretable disorders at 60 months. The results of the trial demonstrate that the EBRT and SBRT combination is well tolerated and yields good efficacy results. These data provide a good basis for comparing EBRT and brachytherapy boost to EBRT and SBRT boost in future prospective studies.

Radiation-Induced Amplification of TGFB1-Induced Mesenchymal Stem Cell-Mediated Sodium Iodide Symporter (NIS) Gene 131I Therapy.

The innate tumor homing potential of mesenchymal stem cells (MSCs) has been used for a targeted delivery of the theranostic sodium iodide symporter (NIS) transgene into solid tumors. We have previously shown that external beam radiotherapy (EBRT) results in the enhanced recruitment of NIS-expressing MSCs into human hepatocellular carcinoma (HuH7). In parallel, the tumor-associated cytokine TGFB1 becomes strongly upregulated in HuH7 tumors in response to EBRT. We therefore evaluated the effects of combining focused EBRT (5 Gy) with MSC-mediated systemic delivery of the theranostic NIS transgene under control of a synthetic TGFB1-inducible SMAD-responsive promoter (SMAD-NIS-MSCs) using 123I-scintigraphy followed by 131I therapy in CD1 nu/nu mice harboring subcutaneous human hepatocellular carcinoma (HuH7). Following tumor irradiation and SMAD-NIS-MSC application, tumoral iodide uptake monitored in vivo by 123I-scintigraphy was enhanced as compared with nonirradiated tumors. Combination of EBRT and SMAD-NIS-MSC-mediated 131I therapy resulted in a significantly improved delay in tumor growth and prolonged survival in therapy mice as compared with the combined therapy using CMV-NIS-MSCs or to control groups receiving EBRT or saline only, or EBRT together with SMAD-NIS-MSCs and saline applications. MSC-based NIS-mediated 131I therapy after EBRT treatment dramatically enhanced therapeutic efficacy when a TGFB1-inducible SMAD-responsive promoter was used to drive NIS expression in adoptively applied MSCs. The remarkable therapeutic effect seen is thought to be linked in large part to the enhanced TGFB1 produced in this context, which leads to a highly selective and focused amplification of MSC-based NIS expression within the tumor milieu.

The Stapled Peptide PM2 Stabilizes p53 Levels and Radiosensitizes Wild-Type p53 Cancer Cells.

The tumor suppressor p53 is a key mediator of cellular stress and DNA damage response cascades and is activated after exposure to ionizing radiation. Amplifying wild-type p53 expression by targeting negative regulators such as MDM2 in combination with external beam radiotherapy (EBRT) may result in increased therapeutic effects. The novel stapled peptide PM2 prevents MDM2 from suppressing wild-type p53, and is thus a promising agent for therapeutic combination with EBRT. Effects of PM2 and potential PM2-induced radiosensitivity were assessed in a panel of cancer cell lines using 2D cell viability assays. Western Blot and flow cytometric analyses were used to investigate the mechanisms behind the observed effects in samples treated with PM2 and EBRT. Finally, PM2-treatment combined with EBRT was evaluated in an in vitro 3D spheroid model. PM2-therapy decreased cell viability in wild-type p53, HPV-negative cell lines. Western Blotting and flow cytometry confirmed upregulation of p53, as well as initiation of p53-mediated apoptosis measured by increased cleaved caspase-3 and Noxa activity. Furthermore, 3D in vitro tumor spheroid experiments confirmed the superior effects of the combination, as the only treatment regime resulting in growth inhibition and complete spheroid disintegration. We conclude that PM2 induces antitumorigenic effects in wt p53 HPV-negative cancer cells and potentiates the effects of EBRT, ultimately resulting in tumor eradication in a 3D spheroid model. This strategy shows great potential as a new wt p53 specific tumor-targeting compound, and the combination of PM2 and EBRT could be a promising strategy to increase therapeutic effects and decrease adverse effects from radiotherapy.

Comparing Radiotherapy Versus Surgery in Men with High-Risk Prostate Cancer: An Outcomes-based Analysis

We evaluated outcomes of men with clinically localized high-risk prostate cancer (HRPCa) definitively treated with combined external beam radiotherapy and androgen deprivation therapy (EBRT) versus radical prostatectomy (RP). Men diagnosed with HRPCa definitively treated with either EBRT or RP from 2008-2016 were included in this study. All clinical data were queried from our IRB-approved multi-institutional tumor registry confirming diagnosis of HRPCa as classified by initial prostate-specific antigen (iPSA), clinical T-stage (cT), and biopsy Gleason score (cGS). Survival outcomes, which included freedom from biochemical failure (FFBF), biochemical control (BC), prostate cancer-specific survival (PCSS), and overall survival (OS), were calculated from date of surgery or EBRT completion. BC differed from FFBF only for a subset of RP patients who were biochemically controlled with salvage radiotherapy (SRT). ANOVA and Chi-Square testing were used to identify differences in baseline characteristics between treatment cohorts. Log-rank testing was used to identify survival differences. Multivariate cox regression analysis (MVA) was used to identify clinical predictors of study outcomes. 1528 Men with a median age of 66 were included in this analysis. Median follow-up of EBRT (n=665) and RP (n=863) patients were 61 and 59 months, respectively. Rate of ADT use with EBRT was 86%. One third of RP patients received post-operative radiotherapy (PORT), with the majority receiving SRT. Comparison of baseline characteristics showed that EBRT patients presented with higher age, iPSA, cT, cGS, and percentage of positive biopsy cores (PPC) compared to RP patients. At seven years, EBRT patients had superior FFBF (50% v. 40%, p<0.001) and equivalent BC (50%) compared to RP patients. EBRT patients had worse OS (71% v. 88%, p<0.001). EBRT patients had worse PCSS at seven years (91% v. 95%), however this difference was not statistically significant (p=0.07). MVA demonstrated that higher iPSA, PPC, cT, cGS, and treatment with RP were associated with worse FFBF and BC. Higher age, PPC, and cGS were associated with worse PCSS. Higher age, PPC, cT, and treatment with EBRT were associated with worse OS. For EBRT patients, ADT use was associated with better FFBF. Hypofractionation was not associated with outcomes. For RP patients, choice of RP technique was not associated with outcomes. Despite having worse disease characteristics at baseline, men who received EBRT had superior FFBF, equivalent BC, and similar PCSS compared to men who underwent RP. A PORT rate of 33% suggests that additional therapy was necessary to achieve similar long-term oncologic outcomes in men treated with RP compared to EBRT. These findings highlight the utility of EBRT in the management of HRPCa.

Patient-reported health-related quality of life up to three years after the treatment with permanent brachytherapy: Outcome of the large-scale, prospective longitudinal study in Japanese–Prostate Cancer Outcome Study by Permanent I-125 Seed Implantation (J-POPS)

PurposeTo evaluate long-term health-related quality of life (HRQOL) impact of I-125 permanent seed implantation (PI) in Japanese patients with localized prostate cancer. Materials and MethodsThis is a longitudinal, prospective study of 2353 patients who enrolled in the nationwide Japanese–Prostate Cancer Outcome Study by Permanent I-125 Seed Implantation (J-POPS) from July 2005 to June 2007. HRQOL was measured before and after treatment (3, 12, 24, and 36 months) using the Medical Outcomes Study 8-items Short-Form Health Survey (SF-8) and the Expanded Prostate Cancer Index Composite Japanese version questionnaire. ResultsOf the total of 1511 patients who returned anonymized HRQOL questionnaires to Translational Research Center for Medical Innovation, 1079 underwent PI alone (PI group) and 432 underwent combined PI and external beam radiation therapy (EBRT) treatment (EBRT combination therapy group). The mental component summary score of SF-8 was improved at 12, 24, and 36 months compared with the pretreatment level. Although the urinary summary score at 3 months in the PI group was significantly lower than that in the EBRT combination therapy group, which recovered thereafter and was comparable to the score of the EBRT combination therapy group. The bowel summary score in the PI group was significantly higher than that in the EBRT combination therapy group at 12, 24, and 36 months. ConclusionThis longitudinal, large-scale prospective study indicated that the general HRQOL for PI was almost maintained 3 years after treatment. These results provide important information for patients with localized prostate cancer, who may select to receive I-125 brachytherapy.

Impact of different adjuvant radiotherapy modalities on women with early-stage intermediate- to high-risk endometrial cancer

ObjectiveVaginal brachytherapy was recommended for patients with intermediate-risk endometrial cancer, however, optimal radiotherapy modalities for intermediate-high- or high-risk patients remains controversial. Previous studies have mainly focused on survival outcomes and...

Appropriate Methodology for EBRT and HDR Intracavitary/Interstitial Brachytherapy Dose Composite and Clinical Plan Evaluation for Patients With Cervical Cancer

PurposeThis study assessed the appropriateness of full parameter addition (FPA) methods with respect to the 3-dimensional deformable dose composite method for evaluating combined external beam radiation therapy (EBRT) and intracavitary brachytherapy (ICBT). Methods and MaterialsA total of 22 patients who received EBRT and high-dose-rate ICBT were retrospectively evaluated. Split-ring and tandem applicators were used for all patients. Additional interstitial needles were used for 5 patients to supplement the implant. Deformable image registrations were performed to deform the secondary EBRT and ICBT planning computed tomography (CT) images onto the reference CT from the third fraction of ICBT. The Dice similarity coefficient was used to evaluate the quality of deformable registration. Doses were transferred to the reference CT, scaled to the equivalent dose in 2-Gy fractions and combined to create the dose composite. Eight dose-accumulation methods were evaluated and compared. D2cc and D0.1cc for organs at risk were investigated. ResultsThe differences in D2cc for rectum, bladder, sigmoid, and bowel between the FPA method for whole-pelvis EBRT and ICBT, calculated using an old American Brachytherapy Society worksheet (FPA_Eh + I_old) and deformable composite for EBRT with boosts and ICBT (Def_E + B + I) were –2.19 ± 1.37 Gyα/β = 3, –0.64 ± 1.13 Gyα/β = 3, –2.06 ± 2.71 Gyα/β = 3, and –1.59 ± 0.89 Gyα/β = 3, respectively. The differences in D2cc for rectum, bladder, sigmoid, and bowel between the new ABS worksheet (FPA_Eh + B + I_abs) and the Def_E + B + I method were 1.21 ± 1.22 Gy α/β = 3, 1.93 ± 1.38 Gyα/β = 3, 0.72 ± 1.12 Gyα/β = 3, and 1.19 ± 1.46 Gyα/β = 3, respectively. Differences in dose-volume histogram parameter values among Def_E + B + I and other FPA methods were not statistically significant (P > .05). ConclusionsCompared with the FPA-based method, deformable registration–based dose composites demonstrated lower OAR D2cc and D0.1cc values; however, the differences were not statistically significant. The current ABS-recommended FPA-based sheet can serve as an acceptable plan evaluation tool for clinical purposes.

Biochemical outcomes and predictive factors by risk group after permanent iodine-125 seed implantation: Prospective cohort study in 2,316 patients

PurposeTo evaluate the biochemical freedom from failure (bFFF) by risk group and treatment modality and the predictive factors of bFFF by risk group in patients with prostate cancer undergoing permanent seed implantation (PI) with or without external beam radiation therapy (EBRT) in a nationwide prospective cohort study (Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 [I-125] Seed Implantation) in Japan during the first 2 years. Methods and MaterialsThe analyses included 2,316 participants in 42 institutions; bFFF was evaluated using the Phoenix definition and calculated using the Kaplan–Meier method, and the Cox proportional hazards model was used to identify the factors associated with bFFF. ResultsMedian followup period was 60.0 months. The 5-year bFFF rates in all patients, 1,028 low-risk patients, 1,114 intermediate-risk patients, and 133 high-risk patients were 93.6%, 94.9%, 92.7%, and 91.1%, respectively. The 5-year bFFF rates in the PI group and EBRT combination therapy group were 93.7% and 93.3%, respectively. In a multivariate analysis, younger age, higher Gleason score (GS), higher percent positive biopsies (%PB), and lower prostate V100 (p = 0.0012, 0.0030, 0.0026, and 0.0368) in all patients; younger age, higher pretreatment prostate-specific antigen, and lower prostate V100 (p = 0.0002, 0.0048, and 0.0012) in low-risk patients; higher GS, higher %PB, and no hormonal treatment (p = 0.0005, 0.0120, and 0.0022) in intermediate-risk patients; and higher GS and higher %PB (p = 0.0329 and 0.0120) in high-risk patients were significantly associated with bFFF. ConclusionsPI with or without EBRT resulted in excellent short-term biochemical outcomes in all risk groups, especially in high-risk patients. Age, pretreatment prostate-specific antigen, and prostate V100 in low-risk patients; GS, %PB, and hormonal treatment in intermediate-risk patients; and GS and %PB in high-risk patients were independently affected bFFF.

Key factors associated with social distress after prostate cancer: Results from the United Kingdom Life after Prostate Cancer diagnosis study

BackgroundMore men are living following a prostate cancer (PCa) diagnosis. They may need support to maximize the quality of their survival. Physical and psychological impacts of PCa are widely documented. Less is known about social impacts. We aimed to identify key factors associated with social distress following PCa. MethodsThe Life After Prostate Cancer Diagnosis study is a UK national cross-sectional survey of men 18–42 months post diagnosis of PCa. Men (n = 58 930) were invited to participate by their diagnosing cancer centre including 82% of English NHS Trusts (n = 111) and 100% of all Health Boards in Northern Ireland (n = 5), Scotland (n = 14) and Wales (n = 6). Social distress was measured using the Social Difficulties Inventory (SDI-21), 16 item Social Distress scale with men assigned to ‘socially distressed’/‘not socially distressed’ groups, according to published guidelines. Clinical and sociodemographic variables were collected from self-report and cancer registries. ResultsResponse rate 60.8% (n = 35 823) of whom 97% (n = 29 351) completed the Social Distress scale (mean age = 71.2; SD = 7.88). The proportion of ‘socially distressed’ men was 9.4%. Multivariable logistic regression analysis revealed unemployment versus employment (odds ratio (OR): 11.58 [95% CI 9.16–14.63]) and ≥3 co-morbidities versus none (OR: 5.37 [95% CI 4.61–6.27]) as key associations. Others were Androgen Deprivation Therapy, External Beam Radiotherapy in combination with another treatment, age, prior mental health problems and living in a socio-economically deprived area. ConclusionMost men following PCa are socially resilient. A simple checklist could help clinicians identify men at risk of social distress.

Survival Following Salvage Surgery after Failed Radiotherapy for Penile Cancer: A SEER-Based Study

Objective: Salvage surgery (SS) for penile cancer (PC) is indicated in the management of local failure following radiation therapy (RT). Reports describing survival outcome are rare. This study aims to assess survival outcome of SS following RT failure in PC. Materials and Methods: We used The Surveillance, Epidemiology, and End Results database to identify patients received SS on the penis following RT. Social, demographic and pathological criteria of the patients were gathered. The 1-, 3-, 5-, 10-year survival rates were assessed. Results: Between 1976 and 2013, 17 patients received penile SS following RT. Median age was 65 years (range 47-91 years). The mean follow-up was 51 months (range 3-213 months). Sixteen (94.12%) patients received external beam radiation and 1 (5.88%) received combined external beam radiation with brachytherapy. Tumor histology was squamous cell carcinoma in 16 (94.12%) patients and mucinous adenocar-cinoma in 1 (5.88%). The 1-, 3-, 5- and 10-year overall survival rates were 68.8, 35.7, 35.7 and 10.7%, respectively. The 1-, 3-, 5- and 10-year cancer specific survival rate was 72.7, 48.4, 48.4, and 36.3% respectively. Conclusion: Our results demonstrate, the overall survival of PC patients underwent SS was poor with nearly one third of patients dying within the first year and only one third surviving up to 3 years from the SS.

High dose rate brachytherapy boost for prostate cancer: Biochemical control and the impact of transurethral resection of the prostate and hydrogel spacer insertion on toxicity outcomes.

To examine the long-term outcomes of high dose rate brachytherapy boost (HDR-BT) combined with external beam radiotherapy (EBRT) for intermediate and high-risk prostate cancer patients. Data from 95 patients who underwent combined EBRT (50.4Gy) and HDR-BT to the prostate between 2010 and 2017 were retrospectively analysed. Biochemical progression free survival (bPFS), local recurrence free survival (LRFS), metastatic free survival (MFS) and overall survival (OS) were estimated using Kaplan-Meier method. Regression analysis was conducted to identify important predictors of outcomes. A total of 24 patients received an initial HDR-BT dose of 18Gy in three fractions, with the remaining 71 patients receiving 16Gy in two fractions as per departmental protocol changes. Most patients (88%) received androgen deprivation therapy. A transurethral resection of the prostate (TURP) was performed in 14 patients and hydrogel spacers (HS) were used in 30 patients. Median follow-up was 58months. The 5-year bPFS, LRFS, MFS and OS were 92%, 100%, 92% and 88%. Univariate regression revealed no statistical association between patient characteristics and time to relapse (all P>0.1). Late > grade 2 genitourinary (GU) toxicity was 6.3%. The use of HS or prior TURP had no impact on late GU toxicity. Late Grade 1 gastrointestinal (GI) toxicity was 5.3%. The combined HDR-BT with EBRT resulted in excellent bPFS. The cumulative risk of late GU and GI toxicity was low and can be further improved with preventative strategies such as a pre-emptive TURP and/or HS insertion.

Long-term results of Perioperative High Dose Rate Brachytherapy (PHDRB) and external beam radiation in adult patients with soft tissue sarcomas of the extremities and the superficial trunk: Final results of a prospective controlled study

BackgroundTo analyze toxicity, patterns of failure, and survival in 106 adult patients with soft tissue sarcomas of the extremity and the superficial trunk treated in a prospective controlled trial of combined Perioperative High Dose Rate Brachytherapy (PHDRB) and external beam radiotherapy (EBRT). MethodsPatients were treated with surgical resection and 16 Gy or 24 Gy of PHDRB for negative or close/positive margins, respectively. EBRT (45 Gy) was added postoperatively. Adjuvant chemotherapy was given to selected patients with high-grade tumors. ResultsThe median follow-up was 7.1 years (range, 0.6–16.0). Grade ≥3 adverse events were observed in 22 patients (20.8%), and grade ≥4 events in 14 patients (13.2%). No grade 5 events were noted. Multivariate analysis (p = 0.003) found that Grade ≥3 toxic events increased with increasing implant volume (TV100). Local control, locoregional control, and distant control rates at 5 and 10 years were 89% and 87%, 82% and 80% and 75% and 69%, respectively. Multivariate analysis (p = 0.024) found that positive margins correlated with decreased local control. Disease-free survival and overall survival rates at 5 and 10 years were 64% and 59% and 73% and 62%, respectively. In multivariate analysis, disease-free survival rates decreased with increasing tumor size (p = 0.0001) and inadequate margins (p = 0.024), and overall survival decreased with increasing tumor size (p = 0.001) and male gender (p = 0.039). ConclusionsThe combination of conservative surgery, high-dose PHDRB, and EBRT produces adequate function and local control in the majority of patients with soft tissue sarcomas of the extremities and the superficial trunk, including a substantial percentage of cases with positive margins. Patients with larger tumors are at a higher risk of complications, treatment failure, and cancer-related death and require an individualized treatment approach.

Variations in patterns of concurrent androgen deprivation therapy use based on dose escalation with external beam radiotherapy vs. brachytherapy boost for prostate cancer

PurposeRetrospective data suggest less benefit from androgen deprivation therapy (ADT) in the setting of dose-escalated definitive radiation for prostate cancer, especially when a combination of external beam radiotherapy (EBRT) and brachytherapy approaches are used. This study aimed to test the hypothesis that patients with prostate cancer with intermediate- or high-risk disease undergoing extreme dose escalation with a brachytherapy boost are less likely to receive ADT. Methods and MaterialsData from the National Cancer Database were extracted for men aged 40–90 years diagnosed with node-negative, non-metastatic prostate cancer from 2004 to 2015. Only patients with intermediate- or high-risk disease who were treated with definitive radiotherapy were included. The association and patterns of care between dose escalated radiotherapy and ADT receipt were assessed using multivariable logistic regression. ResultsPatients with unfavorable intermediate- and high-risk prostate cancer were significantly less likely to receive ADT if they underwent dose escalation with a combination of EBRT and brachytherapy (odds ratio 0.67, p < 0.0001). Over time, this decrease in ADT utilization has widened for patients with unfavorable intermediate-risk disease. There was no difference in ADT utilization when comparing patients treated with non–dose-escalated EBRT to those treated with dose-escalated EBRT (without brachytherapy). ConclusionIn this large national database, patients with unfavorable intermediate- and high-risk prostate cancer were significantly less likely to receive guideline-indicated ADT if they underwent extreme dose escalation with combined radiation modalities. As we await prospective data guiding the utility of ADT with dose escalated radiation, these findings suggest potential underutilization of ADT in patients at higher risk of advanced disease.

Prostate radiotherapy effects on testosterone levels: an empirical investigation

There is a paucity of clinical data to support the hypothesis that external beam radiation therapy causes iatrogenic hypogonadism in prostate cancer patients. All prostate cancer patients treated at a single institution with radiation therapy between 2002 and 2010 were retrospectively evaluated. Patients treated with brachytherapy alone received 0 Gy of external beam radiation therapy and served as the control group. Patients treated with combination external beam radiation therapy + brachytherapy, or external beam radiation therapy alone were categorized into groups who received 45–54 Gy or > 60 Gy of external beam radiation therapy, respectively. Serum testosterone levels were routinely measured with prostate-specific antigen tests. The median follow-up periods for 149 evaluable patients in the control group (0 Gy), the 45–54 Gy group, and > 60 Gy group were 57, 62, and 55 months, respectively (p = 0.43). Among patients who underwent external beam radiation therapy, 53% were treated with intensity-modulated radiation therapy, 65% with pelvic lymph node coverage, and 78% with 18 megavoltage photons. There were no differences in serum testosterone level declines over time between the 45–54 Gy group (p = 0.32) or the > 60 Gy group (p = 0.14) when compared to the control group (0 Gy). While body mass index was associated with baseline testosterone levels in univariate analysis (p < 0.0001), it was not associated with the rate of change following radiation therapy (p = 0.6). Empirical evidence does not support the hypothesis that incidental exposure of the testicular Leydig cells from scattered photons and/or daily portal imaging affects testosterone levels.

External beam radiation therapy and brachytherapy boost versus radical prostatectomy and adjuvant radiation therapy for high-risk prostate cancer.

21 Background: Previous studies have suggested that combination external beam radiation therapy (EBRT) with brachytherapy boost (BT) for high-risk prostate cancer is associated with equivalent overall survival (OS) compared with radical prostatectomy (RP). However, it is not known whether RP with post-operative radiation therapy (PORT) can offer improved OS compared with combination RT (EBRT + BT + androgen deprivation therapy [ADT]) for patients with Gleason 9-10 high-risk disease. Methods: We identified all patients diagnosed with clinical T1-T3, Gleason 9-10, prostate-specific antigen (PSA) 0-40 ng/mL, and clinically node negative disease between 2004 and 2014 from the National Cancer Database. We divided patients into 4 treatment groups: EBRT + ADT, combination RT (EBRT + BT + ADT), RP, and RP + PORT. Only patients who received PORT within 360 days of surgery were included within the RP + PORT group. We compared OS utilizing inverse probability of treatment-weighted multivariable Cox proportional hazards regression modeling after accounting for clinical and demographic factors, including Gleason grade (9 versus 10), T-stage (T1, T2, T3), age, Charlson-Deyo comorbidity score (0, 1, versus 2), education quartile, income quartile, geographic location within the US, insurance status, facility volume, and race. Results: Median follow-up in the entire cohort was 4.5 years. The numbers of patients treated with EBRT + ADT, EBRT + BT + ADT, RP, RP + PORT were 6778, 924, 7111, and 1929, respectively. There were no significant differences in 5-year OS when comparing combination RT to RP (85.0% vs 85.7%, adjusted hazard ratio (AHR) 0.92, 95% confidence interval [CI] 0.77-1.10, p = 0.36) or RP + PORT (85.0% vs 85.6%, AHR 0.89, 95% CI 0.71-1.12, p = 0.34). Combination RT was associated with superior 5-year OS compared to EBRT + ADT alone (without BT boost) (85.0% vs 79.4%, AHR 1.26, 95% CI 1.07-1.48, p &lt; 0.01). Conclusions: Our study suggests that for patients with Gleason 9-10 tumors, multi-modality surgical therapy is equivalent to combination RT.

MRI-guided prostate brachytherapy dose escalation to the dominant intraprostatic lesions: A retrospective analysis of urinary toxicity and biochemical response.

47 Background: Magnetic resonance imaging (MRI) allows for delineation of the dominant intraprostatic lesions (DIL) thus minimizing the risk of a geographic miss. At our center, using MRI planning following the brachytherapy implant, the DIL is defined as the gross tumor volume (GTV) and receives at least the prescribed dose. This retrospective analysis studies the biochemical response and urinary symptoms of a MRI-guided escalated dose to the DIL during prostate brachytherapy. Methods: Intermediate- or high-risk patients with a visible DIL on the diagnostic MRI, treated between 2013 and 2016, with combined external-beam radiation therapy (46 Gray) and a high-dose rate whole prostate brachytherapy (15 Gray), were analyzed. Baseline characteristics and dosimetric values were obtained as well as PSA and International prostate symptom score (IPSS) at baseline, 3, 6, 12, 18, 24, 36 and 48 months (mos). Results: A total of 117 patients were studied, of which 58% were intermediate-risk and 42% high-risk. Median follow-up was 31 months (10-69 months). The biochemical progession-free survival (bPFS) was 97.4%. The median GTV D100 (dose to 100% of the GTV) and CTV V100 (percentage of the clinical target volume, defined as the whole prostate, receiving 100% of the prescribed dose) were 119% and 97.97%. The median PSA at 12, 24, 36 and 48 months for all patients and for patients treated without androgen deprivation therapy (ADT), was 0.18, 0.11, 0.06, 0.07 μg/L, and 0.73, 0.35, 0.1, 0.08 μg/L, respectively. The median IPSS score at baseline was 6 and remained stable over time. Conclusions: MRI-guided dose escalation to the GTV during brachytherapy boost yields an excellent bPFS and a rapid PSA drop without an increase in urinary symptoms. [Table: see text]

Improving rectal dosimetry for patients with intermediate and high-risk prostate cancer undergoing combined high-dose-rate brachytherapy and external beam radiotherapy with hydrogel space.

PurposeTo report on rectal dosimetric and toxicity outcomes of intermediate and high-risk prostate cancer patients undergoing combined high-dose-rate (HDR) brachytherapy and external beam radiotherapy (EBRT) with or without hydrogel spacer (HS) insertion.Material and methodsA total of 97 patients were analyzed in this study, with 32 patients (33%) who had HS insertion compared with a preceding group of 65 patients (67%) without HS. HS safety, the dosimetric effects on organs at risk (rectal, urethral, penile bulb, and bladder) as well as gastrointestinal (GI) and genitourinary toxicity were evaluated and compared between the two groups.ResultsThe median prostate-rectal separation achieved with HS was 10 mm (range, 5-14 mm). There were no post-operative complications following HS insertion. Patients with HS had significantly lower radiation dose to the rectum across all rectal dose volumes from rV30 to rV80, whether in absolute volume (cc) or as percentage of contoured OAR (p < 0.001). There was also significantly less acute > grade 1 GI toxicity (12.5% vs. 30.8%, p = 0.05) and a trend towards less late grade 1 GI toxicity (0% vs. 7.7%; p = 0.11) in the HS group compared to the non-HS group.ConclusionsInsertion of HS in prostate cancer patients receiving combined HDR and EBRT is safe and has resulted in a significant radiation dose reduction to the rectum, resulting in significantly less acute GI toxicity and a trend towards less late GI toxicity.

Radioterapia Externa Exclusiva en Carcinoma Invasor Avanzado del Cuello del Útero.

Introducción: Una combinación de radioterapia de haz externo y braquiterapia es el estándar de manejo radiante radical para el cáncer cervical avanzado. Algunas pacientes no pueden recibir braquiterapia, por lo que se administran mayores dosis de radioterapia externa exclusiva. Se describen los resultados obtenidos con dicha modalidad terapéutica.&#x0D; Métodos: En un estudio retrospectivo, descriptivo, entre Julio de 1997 y Agosto del 2005, se evalúa pacientes mayores de 18 años, tratadas en el Instituto del Cáncer de Solca Núcleo de Loja con el diagnóstico inicial de cáncer cervical estadio III B y IVA. Se caracterizan variables: edad, estadio, respuesta al final del tratamiento, tiempo global de tratamiento, sobrevida global, morbilidad tardía y complicaciones. Se presenta los datos usando medidas de resumen de tendencia central y la curva de supervivencia mediante el método Kaplan Meier: Se utilizó el paquete estadístico SPSS 20.0.&#x0D; Resultados: 25 pacientes con una mediana de edad de 65 años, con cáncer en estadios IIIB y IV recibieron una media de 68 Gy con radioterapia externa exclusiva, en una mediana de 65 días de tiempo global de tratamiento. Hubo respuesta clínica completa en 9 pacientes (36 %); residual tumoral clínico en las 16 restantes (64 %). A los 5 años de seguimiento, 6 pacientes (24 %) se encontraban vivas, sin datos de actividad tumoral locorregional, en las 19 pacientes restantes (76 %), hubo falla locorregional.&#x0D; Conclusión: La radioterapia externa exclusiva no ofrece resultados satisfactorios. Debe insistirse en la necesidad de braquiterapia para alcanzar dosis curativas.

Intraoperative radiation therapy for the treatment of recurrent retroperitoneal and pelvic tumors: a single-institution analysis

BackgroundPatients with recurrent retroperitoneal and pelvic region tumors often require multimodal therapies. Intraoperative radiation therapy (IORT) can deliver high-dose radiation to tumor beds, even if first-line external beam radiation therapy (EBRT) was administered. We evaluated local control (LC) and survival in patients receiving IORT for recurrent tumors.MethodsWe retrospectively analyzed 41 patients with isolated pelvic or retroperitoneal recurrences of colorectal, gynecological, or retroperitoneal primary tumors. Following salvage surgery, all patients underwent tumor bed IORT via electron beam or high dose rate brachytherapy. Isolated IORT (median dose: 15 Gy) was administered to patients who had received first-line EBRT; other patients received IORT (median dose 12 Gy) plus EBRT. Local (LF), regional (RF), and distant failures (DF) were evaluated, and the Kaplan–Meier method and log-rank test were used to evaluate and compare overall survival (OS) from the date of IORT.ResultsForty-one patients underwent 44 treatments, including 27 (61.3%) isolated IORT and 17 (38.7%) IORT and EBRT combination regimens. The median follow-up was 8.1 years (range: 4.4–11.7 years), and the 2, 5, and 8 year overall LC rates were 87.9, 64.0, and 49.8%, respectively. Regarding resection status, the respective 2, 5, and 8 year LC rates were 90, 76, and 76% for R0 resection and 75, 25, and 0% for R1 resection (p < 0.001). The 2, 5, and 8 year OS rates were 68, 43, and 26%, respectively. OS was better among patients with LC (p < 0.001). Twenty-four patients (58.5%) experienced a DF, and the 5 year OS rates for the patients with and without DF were 36 and 52%, respectively (p = 0.04).In a multivariate analysis, LF (p = 0,012) and recurrent retroperitoneal sarcoma (p = 0,014) were identified as significant predictors of worse OS. Thirteen patients (31%) developed clinically treatable complications related to IORT.ConclusionsMany patients achieve long-term OS and LC without significant morbidity after salvage surgery and IORT, especially in case of clear margins.

Changes in lower urinary tract symptoms after iodine-125 brachytherapy for prostate cancer

PurposeTo investigate chronological changes in lower urinary tract symptoms (LUTS) in patients who received iodine-125 brachytherapy (BT) for prostate cancer. MethodsWe enrolled 706 patients who received BT. Of these, 265 (38%) received BT combined with external beam radiation therapy (EBRT). An International Prostate Symptom Score (IPSS), IPSS quality of life (IPSS-QOL) score, and overactive bladder symptom score (OABSS) were recorded before BT (baseline, BL), and 1, 3, 6, 12, 24, 36, 48, and 60 months after BT. The sum of frequency (2), urgency (4) and nocturia (7) of the IPSS questionnaire was defined as the storage symptoms score, whereas the sum of emptying (1), intermittency (3), weak stream (5), and hesitancy (6) was defined as the voiding symptom score. ResultsTotal IPSS significantly increased at 3 months following BT compared with BL (mean score: 17.1 vs. 7.99, P < 0.001) and returned to BL by 36 months. The storage symptom score did not return to BL 36 months after BT. Total OABSS significantly increased 3 months after BT compared with BL (mean score: 6.52 vs. 3.45, P < 0.001), and returned to BL 48 months after BT. The IPSS-QOL score was the highest score (mean score: 2.46 vs. 3.9, P < 0.001) 3 months after BT and returned to BL 48 months after BT, however the IPSS-QOL score was lower than BL (mean score: 2.01 vs 2.46, P < 0.001) at 60 months. The risk factors for LUTS within 1 year after BT were BL IPSS (P < 0.001) and PV (P < 0.001). Patients who received combined EBRT experienced transient storage symptoms 24 and 36 months after BT, whereas those who received BT alone did not. However, the storage symptom score of the patients who received combined EBRT was improving 48 months after BT and eventually showed no significant difference compared with those treated with BT alone. ConclusionThree months after BT, LUTS, including storage symptoms, deteriorated the most but improved with time. The urinary symptom in patients who received combined EBRT can potentially flare again in 24 and 36 months after BT. Knowledge of changes in LUTS associated with BT may influence treatment recommendations and enable patients to make better-informed decisions.