Beam Radiotherapy In Patients Research Articles

Comparison of the effectiveness of intraoperative radiotherapy with external beam radiotherapy in patients with early breast cancer

Background. Breast cancer is the most common cancer in women. The main treatment for breast cancer includes surgery, chemotherapy, radiation therapy, and hormone therapy. The role of radiation therapy in the management of breast cancer continues to evolve. Radiation therapy is currently being de-escalated to include the use of intraoperative radiotherapy (IORT) and adjuvant endocrine therapy. Purpose of the study: to compare the efficacy of IORT with that of external beam radiotherapy (EBRT) in the treatment of early breast cancer. Material and Methods. A retrospective study of 559 patients with early breast cancer was conducted in Clinical Oncology Center of Saint Petersburg. The main treatment group included 273 patients who underwent breast-conserving surgery with IORT and sentinel lymph node biopsy. The control group included 286 patients who underwent breast-conserving surgery with sentinel lymph node biopsy and EBRT. Results. For all patients, the median follow-up time was 59.1 months (interquartile range: 43.7 to 80.7), the minimum follow-up period was 0.6 months, and the maximum follow-up period was 110.4 months. Recurrence occurred in 18 (6.6 %) patients of the main group and in 8 (2.8 %) patients of the control group. A statistically significant association of biological subtype with survival outcomes was found (p=0.02). The hazard ratio for Luminal B of 1.88 (95 % CI 1.02, 3.46) corresponded to a 65 % chance of an earlier onset of a negative outcome. The hazard ratio for triple-negative breast cancer of 3.01 (95 % CI 1.53, 5.95) corresponded to a 75 % chance of an earlier negative outcome. In the main treatment group, 11 (4 %) patients developed disease progression, and 2 of them died of multiple organ failure. In the control group, disease progression was observed in 18 (6.3 %) patients, 6 of whom died. However, the analysis of overall survival using the Kaplan–Meier curve showed a statistically non-significant log-rank p-value (0.73). The 3-year survival rates were 100 % (100 – 100) in the treatment group and 98.2 % (96.7 – 99.8) in the control group. The 5-yaer survival rates were 99.3 % (97.9 – 100) in the treatment group and 97.8 % (96.2 – 99.6) in the control group. These results showed advantage of IORT over EBRT. Conclusions. Intraoperative radiotherapy is a safe and effective alternative to external beam radiotherapy for early breast cancer.

Survival outcomes and toxicity of adjuvant immunotherapy after definitive concurrent chemotherapy with proton beam radiation therapy for patients with inoperable locally advanced non-small cell lung carcinoma

IntroductionAdjuvant immunotherapy (IO) following concurrent chemotherapy and photon radiation therapy confers an overall survival (OS) benefit for patients with inoperable locally advanced non-small cell lung carcinoma (LA-NSCLC); however, outcomes of adjuvant IO after concurrent chemotherapy with proton beam therapy (CPBT) are unknown. We investigated OS and toxicity after CPBT with adjuvant IO versus CPBT alone for inoperable LA-NSCLC. Materials and methodsWe analyzed 354 patients with LA-NSCLC who were prospectively treated with CPBT with or without adjuvant IO from 2009 to 2021. Optimal variable ratio propensity score matching (PSM) matched CPBT with CPBT + IO patients. Survival was estimated with the Kaplan-Meier method and compared with log-rank tests. Multivariable Cox proportional hazards regression evaluated the effect of IO on disease outcomes. ResultsMedian age was 70 years; 71 (20%) received CPBT + IO and 283 (80%) received CPBT only. After PSM, 71 CPBT patients were matched with 71 CPBT + IO patients. Three-year survival rates for CPBT + IO vs CPBT were: OS 67% vs 30% (P < 0.001) and PFS 59% vs 35% (P = 0.017). Three-year LRFS (P = 0.137) and DMFS (P = 0.086) did not differ. Receipt of adjuvant IO was a strong predictor of OS (HR 0.40, P = 0.001) and PFS (HR 0.56, P = 0.030), but not LRFS (HR 0.61, P = 0.121) or DMFS (HR 0.61, P = 0.136). There was an increased incidence of grade ≥3 esophagitis in the CPBT-only group (6% CPBT + IO vs 17% CPBT, P = 0.037). ConclusionThis study, one of the first to investigate CPBT followed by IO for inoperable LA-NSCLC, showed that IO conferred survival benefits with no increased rates of toxicity.

Hypofractionated versus conventional fractionation external beam radiotherapy in intermediate and high risk localized prostate cancer

BackgroundProstate cancer is the second most common malignancy in men, and its incidence is increasing which is attributed to increased screening programs. The treatment options of intermediate and high risk prostate cancer include radical prostatectomy, radiotherapy and androgen deprivation therapy. Hypofractionated radiotherapy is becoming more popular lately due to better understanding of the radiobiology of prostate cancer and favorable logistics.ObjectiveTo compare the toxicity and efficacy of hypofractionated versus conventional fractionation external beam radiotherapy in patients with intermediate and high risk localized prostate cancer treated in Shaukat Khanum Memorial Hospital and Research Center, Lahore (SKMCH & RC).MethodologyWe retrospectively conducted this study on histopathologically confirmed 114 patients with prostate adenocarcinoma who underwent treatment from January 2013 till December 2018. These patients were treated with radical radiotherapy along with hormonal therapy as per indication. Data was collected from electronic hospital system and analyzed by SPSS version 23.Results114 patients were selected according to the inclusion criteria. Mean age was 68 years (61–75). 88% of patients had stage III-IVA disease at the time of diagnosis. Mean PSA and GS was 33 ± 39 SD and 7 ± 0.9 SD respectively. 89% (n = 102) received radiotherapy with 69% of patients receiving dose of 60 Gy in 20 fractions. Among patients who received hypofractionated dose, 86% (n = 61) of them were categorized as high risk and 14% (n = 10) were intermediate risk, whereas among conventional group 90% (n = 28) were high risk patients and 10% (n = 3) were of intermediate risk. In hypofractionated dose group, 14% (n = 10) developed grade 2 proctitis and 8% (n = 6) developed grade 2 cystitis, in contrast to conventional dose group in which only 3 patients (5%) developed grade 2 GI toxicity and 2 patients (2.9%) had grade 2 GU toxicity. However, these toxicities and their grade were clinically insignificant when compared with the dose groups (p = 0.11). 5 year overall survival for hypofractionated radiotherapy versus conventional dose was 100% and 90% respectively with 95% Cl and p value of 0.3 (clinically insignificant), whereas 5 year disease free survival was 100% and 75% for hypofractionation versus conventional EBRT respectively with 95% CI and p value of 0.04 (clinically significant).ConclusionHypofractionated radiotherapy in patients with intermediate and high risk localized prostate cancer has better disease free survival at the expense of higher risk for proctitis and cystitis but no difference in overall survival as compared to conventional dose of radiation.

Outcomes after Proton Beam Irradiation in Patients with Choroidal Melanoma Eligible for Investigational AU-011 Treatment

Introduction: Vision loss is common in patients treated with radiotherapy for uveal melanoma. With proton beam irradiation (PBI), the prescribed dose is delivered to the tumor with a sharp dose reduction outside the target volume. However, radiation complications are likely to develop when tumors are located near the optic nerve or fovea. Treatment with light-activated AU-011 (belzupacap sarotalocan), an investigational drug which specifically targets tumor cells, may avoid these complications. We evaluated outcomes in a historical group of patients who fit eligibility criteria for AU-011 therapy and were treated with PBI. Methods: A consecutive series of patients who received PBI for small choroidal melanoma at a single center between 1986 and 2016 were identified. Consistent with eligibility criteria in clinical trials of AU-011, patients were included when tumor dimensions did not exceed 2.5 mm in maximum thickness and 10.0 mm in largest basal diameter (LBD). Snellen visual acuities were converted to logMAR for analysis. Visual acuity outcomes were analyzed in patients with an initial acuity of logMAR 0.7 or better (equivalent to Snellen 20/100). Rates of visual acuity loss and mortality were calculated using the Kaplan-Meier method. Acuity loss by tumor location was compared using log-rank testing. Rates of tumor recurrence, neovascular glaucoma (NVG), and eye loss were also described. Results: Two hundred and 22 patients were included in the study. The median age was 60.7 years (range 21.3–94.8 years). Median tumor thickness was 2.0 mm (range 1.2–2.5 mm), and median LBD was 8.0 mm (range 4.0–10.0 mm). Median follow-up was 6.9 years (range 1.0–30.2 years). In 204 patients with a baseline logMAR visual acuity of 0.7 or better, the mean baseline acuity was 0.15 (equivalent to Snellen 20/25), which decreased to 0.52 (approximately Snellen 20/70) by 5 years after PBI. Visual outcomes were significantly worse for patients with tumors located within 3 mm of the optic disc and/or fovea. Tumor recurrence (1.4%), NVG (4.5%), and eye loss (2.7%) were uncommon. Discussion: Despite the advantageous dose distribution of protons, over half of patients with small choroidal melanomas located near the optic disc or fovea had a visual acuity equivalent to 20/80 or worse at 5 years after PBI. Treatment with AU-011 may allow better vision preservation in small tumors that carry a high risk of vision loss with radiotherapy.

Risk Modeling for Individualization of the FLAME Focal Boost Approach in External Beam Radiation Therapy for Patients With Localized Prostate Cancer

The FLAME trial (NCT01168479) showed that isotoxic focal boosting to the intraprostatic lesion(s) in patients with intermediate- and high-risk prostate cancer improves 5-year disease-free survival (DFS). Although the near-minimum dose to the gross tumor volume (D98%) was associated with improved outcomes, a closer look suggested that this might not be the same for all patients. Therefore, we investigated whether risk factors that are associated with a benefit of focal boosting can be identified. We described the distribution of clinical characteristics and the number of high-risk factors with respect to the D98% in 526 FLAME trial patients. We used penalized Cox regression to develop a prediction model. To investigate a potential benefit in patient subgroups, we compared the model-based predictions of 5-year DFS assuming standard whole-gland radiation therapy of 77 Gy to the predictions assuming an additional focal boost with D98% of 95 Gy. Patients with high-risk factors were well represented in the group of 120 patients that received D98% > 85 Gy and showed fewer recurrences compared with the group that received 77 Gy. Applying the model simulating a standard dose of 77 Gy, we predicted a high DFS for grade group (GG) 1 patients, whereas patients with high-risk characteristics appeared to show a low DFS. All risk groups showed a high level of DFS when simulating D98% of 95 Gy. Our results suggest that GG 1 patients already show a low level of failure at a standard dose of 77 Gy, limiting the additional benefit of focal boosting. In contrast, patients with high-risk characteristics, especially GG 4 or 5, show a low 5-year DFS, while focal boosting might improve this substantially. This suggests that reaching a high focal boost dose may be particularly beneficial for these patients.

LBP-25 - Concurrent nivolumab and external beam radiation therapy for patients with advanced hepatocellular carcinoma with vascular invasion: a phase 2, single-arm NEXTRAH trial

LBP-25 - Concurrent nivolumab and external beam radiation therapy for patients with advanced hepatocellular carcinoma with vascular invasion: a phase 2, single-arm NEXTRAH trial

Multiparametric imaging guided HDR interventional radiotherapy (brachytherapy) boost in localized prostate cancer: a multidisciplinary experience.

The aim of this study was to report a monoinstitutional multidisciplinary experience about the use of multiparametric imaging to identify the areas with higher risk of relapse in localized prostate cancer, with the purpose of allowing a biologically planned target dose escalation. We performed a retrospective evaluation of patients diagnosed with prostate cancer who received treatments at our Interventional Oncology Center with interstitial interventional radiotherapy from 2014 to 2022. Inclusion criteria were histologically confirmed localized prostate cancer; and National Comprehensive Cancer Network (NCCN) risk class unfavorable intermediate or high/very high risk. The diagnostic work-up included multiparametric Magnetic resonance imaging (MRI), multiparametric Transrectal ultrasound (TRUS), Positron Emission Tomography Computed Tomography (PET-CT) with choline or PSMA (or alternatively bone scan). All patients were assessed and received one treatment with interstitial high-dose-rate interventional radiotherapy (brachytherapy) delivering external beam radiotherapy (46 Gy). All procedures were performed using transrectal ultrasound guidance under general anesthesia and the prescribed doses were 10 Gy to the whole prostate, 12 Gy to the peripheral zone and 15 Gy to the areas at risk. We report the data of 21 patients who were considered for the statistical analysis with a mean age of 62.5 years. The mean PSA nadir was 0.03 ng/ml (range 0-0.09). So far, no biochemical nor radiological recurrences have been recorded in our series. Regarding acute toxicity, the most commonly reported side effects were G1 urinary in 28.5% of patients and G2 urinary in 9.5%; all recorded acute toxicities resolved spontaneously. We present a real-life experience of biologically planned local dose escalation by interventional radiotherapy (brachytherapy) boost, followed by external beam radiotherapy in patients with intermediate unfavorable- or high/very high risk. The local control and the biochemical control rates are proved to be excellent and the toxicity profile tolerable.

Pegylated Liposomal Mitomycin C Lipidic Prodrug in Combination With External Beam Radiation Therapy in Patients With Advanced Cancer: A Phase 1B Study

To evaluate a formulation of pegylated liposomal mitomycin C lipidic prodrug (PL-MLP) in patients concomitantly undergoing external beam radiotherapy (RT). Patients with metastatic disease or inoperable primary solid tumors requiring RT for disease control or symptom relief, were treated with two courses of PL-MLP (1.25, 1.5 or 1.8 mg/kg) at 21-day intervals, along with 10 fractions of conventional RT or 5 SBRT fractions initiated 1-3 days after the first PL-MLP dose and completed within 2 weeks. Treatment safety was monitored for 6 weeks, and disease status was reevaluated at 6 week-intervals thereafter. MLP levels were analyzed 1h and 24h after each PL-MLP infusion. Overall, 19 patients with metastatic (18) or inoperable (1) disease, received combination treatment, with 18/19 completing the full protocol. Most patients (16) were diagnosed with advanced gastrointestinal tract cancer. One grade 4 neutropenia event possibly related to study treatment was reported; other adverse events were mild or moderate. Of the 18 evaluable patients, 16 were free of radiotherapy target lesion progression at first re-evaluation. Median survival of the entire patient population was 63.3 weeks. Serum MLP level correlated with dose increases and similar long circulating profiles were observed before and after RT. PL-MLP up to 1.8 mg/kg in combination with RT treatment is safe, with a high rate of tumor control. Drug clearance is not affected by radiation. PL- MLP is potentially an attractive option for chemoradiotherapy that warrants further evaluation in randomized studies in the palliative and the curative settings.

SA 6.1 Patient selection, dose and fractionation for external beam radiotherapy in patients with early breast cancer

SA 6.1 Patient selection, dose and fractionation for external beam radiotherapy in patients with early breast cancer

A Phase 1 Trial of Durvalumab in Combination with Bacillus Calmette-Guerin (BCG) or External Beam Radiation Therapy in Patients with BCG-unresponsive Non-muscle-Invasive Bladder Cancer: The Hoosier Cancer Research Network GU16-243 ADAPT-BLADDER Study

BackgroundNovel treatments and trial designs remain a high priority for bacillus Calmette-Guerin (BCG)-unresponsive non–muscle-invasive bladder cancer (NMIBC) patients. ObjectiveTo evaluate the safety and preliminary efficacy of anti–PD-L1 directed therapy with durvalumab (D), durvalumab plus BCG (D + BCG), and durvalumab plus external beam radiation therapy (D + EBRT). Design, setting, and participantsA multicenter phase 1 trial was conducted at community and academic sites. InterventionPatients received 1120 mg of D intravenously every 3 wk for eight cycles. D + BCG patients also received full-dose intravesical BCG weekly for 6 wk with BCG maintenance recommended. D + EBRT patients received concurrent EBRT (6 Gy × 3 in cycle 1 only). Outcome measurements and statistical analysisPost-treatment cystoscopy and urine cytology were performed at 3 and 6 –mo, with bladder biopsies required at the 6-mo evaluation. The recommended phase 2 dose (RP2D) for each regimen was the primary endpoint. Secondary endpoints included toxicity profiles and complete response (CR) rates. Results and limitationsTwenty-eight patients were treated in the D (n = 3), D + BCG (n = 13), and D + EBRT (n = 12) cohorts. Full-dose D, full-dose BCG, and 6 Gy fractions × 3 were determined as the RP2Ds. One patient (4%) experienced a grade 3 dose limiting toxicity event of autoimmune hepatitis. The 3-mo CR occurred in 64% of all patients and in 33%, 85%, and 50% within the D, D + BCG, and D + EBRT cohorts, respectively. Twelve-month CRs were achieved in 46% of all patients and in 73% of D + BCG and 33% of D + EBRT patients. ConclusionsD combined with intravesical BCG or EBRT proved feasible and safe in BCG-unresponsive NMIBC patients. Encouraging preliminary efficacy justifies further study of combination therapy approaches. Patient summaryDurvalumab combination therapy can be safely administered to non–muscle-invasive bladder cancer patients with the goal of increasing durable response rates.

Outcomes of salvage high dose-rate brachytherapy with or without pelvic external beam radiotherapy in patients with palpable local recurrence of prostate cancer after radical prostatectomy

PurposeThis study aims to evaluate the outcomes and toxicities in patients with palpable local recurrence of prostate cancer after radical prostatectomy (RP), who were treated with salvage high dose-rate brachytherapy (HDR-BT) with or without pelvic external beam radiotherapy (EBRT). MethodsThis retrospective review included patients with palpable local recurrence of prostate cancer after RP who underwent salvage HDR-BT at a single institution between 2002 and 2020. HDR-BT regimens included 950 cGy x 2 (N = 4) or 1500 cGy x 1 (N = 2) combined with EBRT; or monotherapy with 950 cGy x 4 (N = 1) or 800 cGy x 2 (N = 1). Toxicity was graded according to CTCAE Version 5.0. ResultsA total of 8 patients were included. Median follow-up was 49 months (range: 9–223 months). Median age at time of salvage brachytherapy was 68 years (range: 59–85 years). Seven out of 8 patients were alive at last follow-up. There have been no locoregional recurrences. Three patients developed distant metastatic disease. One patient developed acute grade 3 urinary obstruction requiring catheterization, which lasted for 1 day postbrachytherapy. One patient developed late grade 3 urinary incontinence 18 months after brachytherapy. There were no other grade 2+ toxicities. ConclusionsThis study demonstrates the safety and efficacy of salvage HDR-BT in the setting of palpable local recurrence of prostate cancer after RP, with durable locoregional control and acceptable rates of toxicity. HDR-BT should be further explored as an option for dose-escalated salvage radiotherapy after prior radical prostatectomy.

Phase II Study of Pembrolizumab and Fractionated External Beam Radiotherapy in Patients with Relapsed and Refractory Large B-Cell Lymphoma

Background: Relapsed/refractory (R/R) large B-cell lymphoma (LBCL) poses a therapeutic challenge, however immune based interventions are changing the landscape of salvage therapy. Manipulation of immune checkpoint pathways involving programmed cell death protein 1 (PD-1) and its ligands PD-L1/PD-L2 can trigger anti-tumor effects in LBCL. However, results with checkpoint inhibitor monotherapy for LBCL have been disappointing with reported overall response rates (ORR) of 10% for patients who experienced relapse after autologous stem cell transplantation (ASCT) and 3% for those ineligible for ASCT (Lesokhin AM et al J Clin Oncol. 2016). Radiation therapy (RT) is highly effective in R/R LBCL and may enhance response when coupled with immune based therapy. We sought to evaluate the efficacy of RT combined with pembrolizumab among patients with R/R non-Hodgkin Lymphoma (NHL) treated with RT to 1-2 sites of refractory disease with at least one index lesion excluded from the RT field for evaluation of abscopal effect. Methods: We conducted a single center, open label, phase II trial of patients with R/R NHL with progressive lymphoma after 2 or more lines of therapy. Eligible patients had PET avid disease amenable to RT and at least one distinct lesion outside of the planned RT field that would serve as the index (abscopal) lesion(s) by which the response to therapy would be defined. Patients were administered a fixed dose of 200 mg of pembrolizumab intravenously every 21 days beginning on day 2 of RT planned for 24 months or until progression. External beam RT was planned to dose of 40-50 Gy in ≤3 Gy fractions. The primary endpoint was ORR (defined as complete and partial response) of the unirradiated lesion(s) at 3 months (after completion of RT and 3 cycles of pembrolizumab). Secondary endpoints included safety, progression free survival (PFS) and overall survival (OS). ORR and dose limiting toxicity (DLT) were monitored simultaneously using Bayesian stopping boundaries based on an ORR of at least 35% at 3 months and DLT rate at cycle one below 30%. A sample size of 20 was planned. Results: Between February 2018 and November 2020, 17 patients were enrolled on the study and received at least 1 cycle of pembrolizumab and at least 1 fraction of RT. The median age was 66 years (range 24 - 83); 29% (n=5) of patients were female. Most patients had LBCL (88%, n=15, double hit, n=5), one patient had PMBCL (6%) and one patient had NK T-cell lymphoma (6%). The median number of prior therapies was 3 (range 2-13) with 53% (n=9) of patients having received ≥3 prior lines of treatment. Eighteen percent (n=3) of patients received prior ASCT and 53% (n=9) received CAR-T cell therapy prior to enrollment. The median number of unirradiated lesions excluded from the RT field was 2 (range 1-24). The median diameter of the largest unirradiated lesion was 2.4 cm (range 1.1 - 8.0 cm). The median RT dose delivered was 45 Gy (range 22.5 -50). The median follow up for the 17 patients was 34.75 months. Sixteen patients had a response assessment, one patient suffered from a stroke and response was not assessed. The ORR was 28% (CR 23% [n=3] and PR 15% [n=2]). Local control within the radiated field was achieved in 11 of the 16 patients (69%). For all 17 patients, the median PFS and OS were 2.7 months and 6.3 months respectively. The 2 year PFS and OS rates were 11.8% and 23.5% respectively (Figure 1). There were 13 deaths, 12 due to lymphoma and 1 due to stroke. For the five responding patients, the median duration of response was 13.3 months (range 5.0 - 50.5 months). Two patients remain in CR 37.6 (PMBCL) and 50.5 (double hit LBCL) months after protocol therapy. The trial was terminated early due to poor accrual. Treatment was generally well tolerated. One of the long term survivors with a history of chronic steroid use experienced grade 4 avascular necrosis in the RT field. Conclusion: In this single center, phase II trial of pembrolizumab and concurrent RT among patients with highly refractory LBCL, local control within the radiation field was encouraging however abscopal responses were minimal. Further exploration of the mechanism behind the exceptional responses in two patients treated with RT and pembrolizumab in this high-risk population is warranted. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The therapeutic efficacy of radical prostatectomy and external beam radiation therapy in patients with different pathological patterns of prostate cancer

BackgroundWe aim to investigate the prognostic value of different pathological patterns of non-adenocarcinoma prostate cancers (PCa) in radical prostatectomy (RP) and external beam radiation therapy (EBRT). MethodsData of 470,258 localized PCa patients between 2004 and 2016 were collected from the Surveillance, Epidemiology, and End Results database. Propensity score matching was performed to balance the baseline characteristics of patients in different groups. Kaplan–Meier curves and Cox regression were used for survival analysis. Overall survival (OS) and cancer-specific survival (CSS) were set as endpoints. ResultsTotally, 1044 patients with non-adenocarcinoma patterns of PCa were included. Patients with small cell neuroendocrine carcinoma (SCNC) and neuroendocrine differentiation (NED) harbored the worst prognosis in both RP and EBRT among all pathological groups. RP exhibited superior effects to EBRT for this group of cases. Ductal carcinoma (DA) was also related to poorer survival outcomes versus PAC in both local therapies. Yet, for men with DA, both RP and EBRT still improved patients' prognosis against no local therapy (NLT), with RP being the superior modality. Cases harboring mucinous adenocarcinoma (MA) and signet ring cell carcinoma (SRCC) shared comparable clinical outcomes to men with PAC. However, for cases with MA, neither RP nor EBRT was related to better survival outcomes against NLT, while for patients with SRCC, both RP and EBRT prolonged patients’ survival with similar effects. ConclusionsOur study provided a comprehensive view of the treatment effect of RP and EBRT in non-adenocarcinoma PCa patients. These findings could facilitate clinicians in making therapeutic decision-making for non-adenocarcinoma patients.

PO50 Presentation Time: 10:00 AM: Long-Term Results of Salvage High Dose-Rate Brachytherapy with or without Pelvic External Beam Radiotherapy in Patients with Palpable Local Recurrence of Prostate Cancer After Radical Prostatectomy

<h3>Purpose</h3> This study aims to evaluate the long term outcomes and toxicities in patients with clinically apparent, gross local recurrence of prostate cancer after radical prostatectomy, treated with salvage high dose-rate brachytherapy (HDR-BT) with or without pelvic external beam radiotherapy (EBRT). <h3>Materials and Methods</h3> Retrospective chart review was performed to identify patients with clinically apparent, gross local recurrence of prostate cancer after radical prostatectomy who underwent salvage HDR-BT at a single institution between 2002 and 2020. HDR-BT regimens included 950 cGy x 2 (N=4), 1500 cGy x 1 (N=2), 950 cGy x 4 (N=1), and 800 cGy x 2 (N=1). Pelvic EBRT was allowed at the discretion of the treating physician. Treatment and clinical characteristics were obtained for each patient, and outcome and toxicity data were collected. Toxicity was graded according to Common Toxicity criteria for Adverse Events Version 5.0. Descriptive analysis was performed. <h3>Results</h3> A total of 8 patients were included in analysis with a median follow-up of 49 months (range: 9 to 223 months). Five (63%) patients presented with a biochemical recurrence, and 3 patients (38%) presented with symptoms including hematuria and urinary obstruction. Seven patients underwent TRUS-guided biopsy which confirmed recurrent adenocarcinoma. The remaining patient underwent a PSMA PET/CT scan revealing a PET-avid soft tissue lesion in the prostate bed, but declined biopsy and proceeded with treatment without pathologic confirmation. Median age at time of salvage brachytherapy was 68 years (range: 59 to 85 years). Median time from prostatectomy to salvage HDR-BT was 95 months (range: 19 to 207 months). Median PSA at time of HDR brachytherapy was 2.32 ng/ml (range: undetectable on ADT to 13 ng/ml). Median lesion size was 2.5 cm (range: 1 to 3.6 cm). Six patients (75%) received adjuvant pelvic EBRT, 45-50 Gy in 25 fractions. Seven out of 8 patients received ADT after salvage brachytherapy for a median duration of 12 months (range: 8 to 24 months). The remaining patient did not receive ADT due to cardiac comorbidities. Seven out of 8 patients were alive at last follow-up. There have been no locoregional recurrences. Three patients developed distant metastatic disease. One patient, who had negative conventional staging scans 3 months prior to brachytherapy, was found to have distant metastatic disease only 2 months after salvage brachytherapy and died due to metastatic prostate cancer 9 months after HDR-BT. The other 2 patients developed distant metastases at 14 and 27 months after brachytherapy. One patient developed late grade 3 urinary incontinence requiring artificial urinary sphincter (AUS) placement 18 months after brachytherapy. This patient had the largest tumor size, 3.6 cm in longest dimension, and received pelvic EBRT in addition to HDR-BT. He is now more than 10 years out from HDR-BT with undetectable PSA and doing well with his AUS. There were no other grade 2 or higher genitourinary or gastrointestinal toxicities. <h3>Conclusions</h3> This study demonstrates the long-term safety and efficacy of salvage HDR brachytherapy in the setting of clinically apparent local recurrence of prostate cancer after radical prostatectomy, with durable locoregional control and acceptable rates of toxicity. HDR-BT should be further explored as an option for dose-escalated salvage radiotherapy in patients with gross local recurrences after radical prostatectomy.

A neuropathic component of tumor-related pain as a predictor of good response to palliative radiotherapy

The recently published ESTRO ACROP guidelines for external beam radiotherapy in patients with uncomplicated [1] and complicated [2] bone metastases will have a major impact on radiotherapy practice for bone metastases. The guidelines for complicated bone metastases state that most studies demonstrating the benefit of radiotherapy in reducing bone metastasis-related pain fail to differentiate the type of pain experienced by patients [2]. The guidelines also state that there is no comparative evidence to evaluate the relative role of treatments such as medication, radiotherapy, and neurostimulation therapy, and hence, no recommendation can be provided regarding the use of radiotherapy [2].

Influence of Timing Between Androgen Deprivation Therapy and External Beam Radiation Therapy in Patients With Localized, High-Risk Prostate Cancer

PurposeTreatment with long-term androgen deprivation therapy (ADT) and radiation therapy (RT) is the nonsurgical standard-of-care for patients with high- or very high-risk prostate cancer (HR-PC), but the optimal timing between ADT and RT initiation is unknown. We evaluate the influence of timing between ADT and RT on outcomes in patients with HR-PC using a large national cancer database. Methods and MaterialsData for patients with clinical T1-T4 N0, M0, National Cancer Comprehensive Network HR-PC who were treated with definitive external RT (≥60 Gy) and ADT starting either before or within 14 days after RT start were extracted from the National Cancer Database (2004-2015). Patients were grouped on the basis of ADT initiation: (1) >11 weeks before RT, (2) 8 to 11weeks before RT, and (3) <8 weeks before RT. Kaplan-Meier, propensity score matching, and multivariable Cox proportional hazards were performed to evaluate overall survival (OS). ResultsWith a median follow-up of 68.9 months, 37,606 patients with HR-PC were eligible for analysis: 13,346 (35.5%) with >11 weeks of neoadjuvant ADT, 11,456 (30.5%) with 8 to 11 weeks of neoadjuvant ADT; and 12,804 (34%) patients with <8 weeks of neoadjuvant ADT. The unadjusted 10-year OS rates for >11 weeks, 8 to 11 weeks, and <8 weeks neoadjuvant ADT groups were 49.9%, 51.2%, and 46.9%, respectively (P = .002). On multivariable and inverse probability of treatment weighting analyses, there was a significant OS advantage for patients in the 8 to 11 weeks neoadjuvant ADT group (adjusted hazard ratio 0.90; 95% confidence interval, 0.86-0.95; P < .001) but not the >11 weeks group. ConclusionsNeoadjuvant ADT initiation 8 to 11 weeks before RT is associated with significantly improved OS compared with shorter neoadjuvant ADT duration. Although prospective validation is warranted, this analysis is the largest retrospective study suggesting an influence of timing between ADT and RT initiation in HR-PC.

Dosimetric study of a hybrid plan technique for external beam radiotherapy in patients with cervical cancer.

The aim of this study was to investigate the effect of a hybrid technique which results from combining intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) for the treatment of cervical cancer patients. Plans made with the hybrid technique and pure IMRT and VMAT were retrospectively compared in 20 patients with cervical cancer at different stages. All plans were made using the same contours based on the original computed tomography (CT) scans. Conformity (CI) and homogeneity (HI) indices of the planning target volumes (PTVs) were calculated for each technique in order to evaluate plan quality. All techniques were compared in terms of dose to organs at risk (OARs), number of monitor units (MUs) and treatment time. It turned out that plans made with the hybrid technique had improved dose conformity and homogeneity compared to plans made only with IMRT and VMAT (p < 0.001). Regarding the OARs, the maximum dose (Dmax) delivered to the bladder, rectum and femoral heads was lower for the hybrid plans compared to the IMRT and VMAT plans (p < 0.001). The volumes irradiated to doses of 50Gy (V50Gy) for rectum, bladder and bowel were lower for the hybrid plans (p < 0.001, p = 0.002). Furthermore, the treatment time and MU values for the hybrid plans were found to be between of the values for the IMRT and VMAT plans. It is concluded that, as compared to IMRT and VMAT plans, the hybrid plan technique allowed a better conformity and homogeneity for the dose distribution in the PTV and a dose reduction to the OARs.

Low and high-dose-rate brachytherapy in combination with external beam radiotherapy for high risk prostate cancer

Background. Prostate cancer (PCa) in the Russian Federation takes the leading place in the prevalence of cancer among the male population.Objective: to investigate the effect of increasing a single focal dose in high-dose-rate brachytherapy (HDR-BT) in combination with external beam radiotherapy on biochemical failure-free survival and local control in patients with high-risk PCa. Materials and methods. The study included 350 men with PCa in the group of high and extremely high risk of progression. All patients included in the study were divided into 4 groups. Groups 1, 2 and 3 included 276 patients who received HDR-BT with a 192Ir source with a single dose per fraction: 10 Gy (n = 83), 12 Gy (n = 46) and 15 Gy (n = 147). Group 4 included 74 patients who received low-dose-rate brachytherapy with 125I sources up to a total focal dose of 110 Gy. At the 2 stage, external beam radiotherapy was a conventional fractionation (single dose of 2 Gy, total - 44-46 Gy).Results. Of 350 patients over a 5-year follow-up period, PCa recurrence was noted in 65 (18.6 %). The 3- and 5-year biochemical failure-free survival rates in the general cohort of patients were 87.4 and 81.4 %. 5-year biochemical failure-free survival was significantly higher in group 3 relative to group 4 and amounted to 89.8 and 74.2 % (p = 0.03). Increasing the dose for HDR-BT from 10 to 12 Gy per fraction significantly reduced the frequency of local relapses from 15.7 % (in group 1) to 2.2 % (in group 2) (p = 0.0001) while maintaining the level of genitourinary and gastrointestinal toxicity. Conclusion. The use of a combination of brachytherapy and external beam radiotherapy in patients with high risk PCa is highly effective in achieving local control of the tumor. The optimal fractionation regime for HDR-BT remains a matter of debate. The use of 15 Gy per fraction for HDR-BT in combination with external beam radiotherapy is the most optimal fractionation regimen in patients with high-risk PCa.

From the Editor's Desk...

From the Editor's Desk...

Brachytherapy for Oesophageal Carcinoma: A Comprehensive Review of Literature and Techniques

AbstractIntroduction:Oesophageal carcinoma is one of the fatal cancers mainly because of its rapid spread and poor prognosis. Treatment modalities involves a multimodality approach, including surgery, radiation therapy and chemotherapy. Radiation therapy includes brachytherapy in the form of intraluminal radiation therapy. Brachytherapy permits delivery of high tumouricidal doses to superficial cancerous growth of the oesophagus while delivering much lower doses to the surrounding tissue. It is mostly given in combination with external beam radiation in patients with poor performance scores not likely to tolerate an aggressive chemoradiation regimen or as a boost to concurrent chemoradiotherapy. It is very effective in terms of local tumour control as well as in relieving symptoms in advanced/recurrent disease. Intraoperative brachytherapy and seed brachytherapy have also been tried to address the nodal disease.Methods:We undertook a review of the available literature and techniques developed in the past three decades to emphasise the role of brachytherapy in curative or palliative settings in the treatment of oesophageal carcinoma.Conclusion:Oesophageal brachytherapy will remain a tangible treatment of oesophageal cancer, although it is less commonly used due to high expertise requirement, lack of established evidence, risk of life-threatening complications and lack of interest in brachytherapy. It offers quick and useful palliation for a prolonged period, along with good quality of life and superior dosimetry. Use of novel applicators may allow dose escalation and lower toxicity. Seed brachytherapy is also emerging as a promising option in nodal recurrences.