High Dose External Beam Radiotherapy Research Articles

Concurrent Atezolizumab Plus Bevacizumab and High-Dose External Beam Radiotherapy for Highly Advanced Hepatocellular Carcinoma.

Atezolizumab plus bevacizumab (atezo-bev) has been recommended for advanced hepatocellular carcinoma (HCC). High-dose external beam radiotherapy (RT) is recognized for its excellent local tumor control. The efficacy and safety of concurrent atezo-bev with RT for highly advanced HCC has been minimally explored. In this preliminary retrospective study, we assessed patients with highly advanced HCC, characterized by Vp4 portal vein thrombosis or tumors exceeding 50% of liver volume, who received concurrent atezo-bev and RT (group A). Group A included 13 patients who received proton radiation at a dose of 72.6 GyE in 22 fractions, and one patient who received photon radiation at a dose of 54 Gy in 18 fractions. This group was compared with 34 similar patients treated atezo-bev alone as a control (group B). The primary objectives were to evaluate the objective response rate (ORR), overall survival (OS), and safety. Baseline characteristics were similar between groups, except for a higher incidence of Vp4 portal vein thrombosis in group A (78.6% vs. 21.4%, P = .05). Group A achieved a higher ORR (50.0% vs. 11.8%, P < .01) and a longer OS (not reached vs. 5.5 months, P = .01) after a median follow-up of 5.2 months. Multivariate analysis indicated that concurrent RT independently favored longer OS (hazard ratio: 0.18; 95% CI, 0.05-0.63, P < .01). Group A did not increase any grade adverse events (78.6% vs. 58.8%, P = .19) or severe adverse events of grade ≥ 3 (14.3% vs. 14.7%, P = .97) compared to group B. The concurrent high-dose external beam radiotherapy appears to safely enhance the effectiveness of atezolizumab plus bevacizumab for highly advanced patients with HCC. Further studies are warranted to confirm these findings.

Safety and Efficacy of Spatially Fractionated Radiation Therapy Using Lattice Radiation for Metastatic and/or Bulky Disease

Spatially fractionated radiation therapy (Lattice) delivers ablative doses to metastatic and/or unresectable tumors with a curative or palliative goal. Through different forms of three-dimensional focusing, lattice forms several spherical high-dose areas(vertices) within the tumor, to produce a more obvious peak-valley effect and limit exposure to surrounding normal tissue. This study aimed to evaluate the efficacy and toxicity of patients with metastatic and/or bulky tumors treated with Lattice radiation. Between April 2017 and February 2021, 76 patients with metastatic or bulky tumors treated with spatially-fractionated high-dose external beam radiation using the Lattice technique were included. A median dose of 15 Gy/1 fraction (range 10-45 Gy in 1/3 fractions) was delivered to the vertices in the gross tumor volumes (GTV). 46 patients were treated with Lattice radiation combined with conventional fractionated external irradiation, and 30 patients were treated with Lattice alone. Patients were evaluated for clinical response, survival, and toxicity. A total of 76 patients with 85 sites were included in the analysis, 63 (82.9%) patients had metastatic diseases. Median GTV was 138.6cc (range 4.9-3784.1cc) in volume and 6.2 cm (range:2.3-21.4cm) in greatest axial diameter. 38 tumors were in the thorax, 13 abdomen/pelvis, 19 metastatic lymph nodes, 8 bone, 5 head and neck, and 2 extremities. The median follow-up was 11.6 months (range 1.27-57.37 months). At the time of analysis, 23 patients (29.9%) were alive, without the progression of disease. 90.7% of the deceased patients died of disease progression. Median overall survival (OS) was 11.4 months (95% CI: 8.4-17.6), the 1-year OS and cancer specific survival were 46.8% and 48.7% respectively. The disease control rate (DCR) was 91.8%, including 2.4% complete remission, 48.2% partial remission, and 41.2% stable disease. Symptomatic improvement was observed in 98.7% of patients. No mortality was associated with Lattice therapy. There was no treatment-associated acute or late grade 3+ toxicity. Lattice radiation is feasible and well-tolerated in the treatment of metastatic and/or bulky diseases, and may provide a high DCR. In light of these preliminary results, it seems that this therapy may be a new paradigm for treating patients with advanced cancers.

Advanced stage cutaneous T-cell lymphoma treated with high-dose external beam radiation therapy: A case report.

The treatment for advanced-stage or refractory cutaneous T-cell lymphoma (CTCL) is largely palliative. Due to the rarity of the disease, there are few randomized controlled trials and large-scale prospective studies. Therefore, the treatment of advanced-stage CTCL remains challenging. A 64-years-old man who had received narrowband UVB phototherapy for several years presented with a generalized rash with widespread polycyclic erosions and painful ulcers on his hands and feet. We restaged him as stage III CTCL. He was treated with high-dose radiation for curative purposes and 3-dimensional conformal radiation therapy to both hands and feet. At the 2-year follow-up after the end of radiotherapy, the irradiated skin had recovered to normal soft, smooth skin with localized fibrosis and hypopigmented skin. He reported an excellent quality of life, and his hands and feet were free to move. CTCL at an advanced stage could require dose escalation with local radiotherapy for curative purposes. High-dose 3-dementional conformal radiation therapy could be effective and has tolerable toxicities.

Superior Post-Treatment Biopsy Outcomes with High Dose SBRT Compared to High-Dose Conventionally Fractionated IMRT for Clinically Localized Prostate Cancer

<h3>Purpose/Objective(s)</h3> To compare post-treatment biopsy outcomes for clinically localized prostate cancer patients treated with high-dose conventionally fractionated intensity modulated radiotherapy (CF- IMRT) versus high-dose stereotactic body radiotherapy (SBRT). <h3>Materials/Methods</h3> 451 patients with low and intermediate risk prostate cancer treated with high dose external beam radiotherapy underwent a post-treatment biopsy which was routinely performed at our institution to assess local control status. Biopsies were performed 2-3 years after completion of radiotherapy. 221 patients were treated with CF-IMRT to a median dose of 75.6 Gy (range: 64.8-86.4) and 230 patients were treated with SBRT to a median dose of 40 Gy in 5 fractions (range: 32.5-42.0). A 6-month course of androgen deprivation therapy (ADT) was used in conjunction CF-IMRT and SBRT in 38% and 17% of patients. The percentage comprising low, favorable intermediate and unfavorable intermediate risk group were similar (CF-IMRT: 23%, 36% and 41%; SBRT: 18%, 49%, 33%). The histological outcome of the prostate biopsy was classified as positive (prostatic adenocarcinoma without typical radiation–induced changes), negative (no evidence of carcinoma) or severe treatment effect. <h3>Results</h3> The incidence of a positive post treatment among the IMRT and SBRT cohorts were 49% and 17%, respectively (p< 0.001). The incidence of a positive biopsy for low risk, favorable- intermediate risk and unfavorable- intermediate risk patients treated with IMRT and SBRT were: IMRT: 40%, 52%, and 52%; SBRT: 7.1%, 17%, and 21%, respectively. Multivariable analysis evaluating co-variates associated with a positive post-treatment biopsy was IMRT (P< 0.001 CI:0.12, 0.33) with 5-fold higher odds of a positive biopsy compared to SBRT. Other variables including the use of ADT and the risk group did not significantly impact on the biopsy outcome. <h3>Conclusion</h3> The use of SBRT in the treatment of low and intermediate risk prostate was associated with improved post-treatment biopsy outcomes compared to conventionally fractionated IMRT. These findings were observed even in the setting of high-dose IMRT to prescribed doses of ≥75.6 Gy. We hypothesize that these findings may be related to the greater ablative potential of high dose SBRT compared to IMRT.

Interplay Between Duration of Androgen Deprivation Therapy and External Beam Radiotherapy With or Without a Brachytherapy Boost for Optimal Treatment of High-risk Prostate Cancer

Radiotherapy combined with androgen deprivation therapy (ADT) is a standard of care for high-risk prostate cancer. However, the interplay between radiotherapy dose and the required minimum duration of ADT is uncertain. To determine the specific ADT duration threshold that provides a distant metastasis-free survival (DMFS) benefit in patients with high-risk prostate cancer receiving external beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT). This was a cohort study of 3 cohorts assembled from a multicenter retrospective study (2000-2013); a post hoc analysis of the Randomized Androgen Deprivation and Radiotherapy 03/04 (RADAR; 2003-2007) randomized clinical trial (RCT); and a cross-trial comparison of the RADAR vs the Deprivación Androgénica y Radio Terapía (Androgen Deprivation and Radiation Therapy; DART) 01/05 RCT (2005-2010). In all, the study analyzed 1827 patients treated with EBRT and 1108 patients treated with EBRT+BT from the retrospective cohort; 181 treated with EBRT and 203 with EBRT+BT from RADAR; and 91 patients treated with EBRT from DART. The study was conducted from October 15, 2020, to July 1, 2021, and the data analyses, from January 5 to June 15, 2021. High-dose EBRT or EBRT+BT for an ADT duration determined by patient-physician choice (retrospective) or by randomization (RCTs). The primary outcome was DMFS; secondary outcome was overall survival (OS). Natural cubic spline analysis identified minimum thresholds (months). This cohort study of 3 studies totaling 3410 men (mean age [SD], 68 [62-74] years; race and ethnicity not collected) with high-risk prostate cancer found a significant interaction between the treatment type (EBRT vs EBRT+BT) and ADT duration (binned to <6, 6 to <18, and ≥18 months). Natural cubic spline analysis identified minimum duration thresholds of 26.3 months (95% CI, 25.4-36.0 months) for EBRT and 12 months (95% CI, 4.9-36.0 months) for EBRT+BT for optimal effect on DMFS. In RADAR, the prolongation of ADT for patients receiving only EBRT was not associated with significant improvements in DMFS (hazard ratio [HR], 1.01; 95% CI, 0.65-1.57); however, for patients receiving EBRT+BT, a longer duration was associated with improved DMFS (DMFS HR, 0.56; 95% CI, 0.36-0.87; P = .01). For patients receiving EBRT alone (DART), 28 months of ADT was associated with improved DMFS compared with 18 months (RADAR HR, 0.37; 95% CI, 0.17-0.80; P = .01). These cohort study findings suggest that the optimal minimum ADT duration for treatment with high-dose EBRT alone is more than 18 months; and for EBRT+BT, it is 18 months or possibly less. Additional studies are needed to determine more precise minimum durations.

Clinical Spectrum and Outcomes of Ocular and Periocular Complications following External-Beam Radiotherapy for Inoperable Malignant Maxillary Sinus Tumors

Purpose: To highlight the clinical spectrum, management, and outcomes of ocular/periocular complications following high-dose external-beam radiotherapy (EBRT) for inoperable malignant maxillary sinus-involving tumors (MMST). Methods: A retrospective, interventional case series. All patients who were diagnosed with inoperable MMST (with orbital involvement) and treated with high-dose fractionated EBRT (65 Gy in 30 fractions) at James Cook University Hospital, UK, were included. Results: Seven patients with advanced MMST (T4aN0M0–T4bN2cM0) were included and were followed up for 23.8 ± 10.2 months. Severe lid margin disease, dry eye, and neurotrophic keratopathy were universally observed. Other complications included cicatricial conjunctivitis (71%), corneal perforation (57%), limbal stem cell deficiency (LSCD; 43%), glaucoma (29%), and superimposed candida keratitis (14%). Amniotic membrane transplant (AMT; 71%), tarsorrhaphy (43%), tectonic keratoplasty (29%), and evisceration (14%) were warranted. Intact corneal epithelium was observed in all patients and good corrected-distance visual acuity (≥20/60) was observed in 3 (43%) patients at final follow-up. Conclusion: High-dose EBRT for inoperable MMST can lead to a wide array of severe ocular/periocular complications. AMT serves as a potentially useful treatment modality to restore the ocular surface integrity after severe radiation keratopathy. We advocate active monitoring for any evolving ophthalmic complications during and after EBRT to enable timely intervention.

Clinical Outcomes And Radiologic Response Of Incompletely Resected Grade 2-3 Meningiomas Treated With External Beam Radiation Therapy

To evaluate the clinical outcomes of incompletely resected grade 2-3 meningiomas treated with definitive external beam radiation therapy (EBRT). Grade 2 or 3 meningioma patients with measurable disease (≥1cm on MRI) who received EBRT after subtotal resection (STR) or biopsy at a tertiary cancer center were retrospectively reviewed. Radiologic response was evaluated using the MacDonald criteria. Local control (LC), progression-free survival (PFS), and overall survival (OS) rates were estimated using the Kaplan-Meier method. Cox regression analysis was performed to identify factors associated with improved LC. Twenty-eight patients with grade 2 (n = 24) or grade 3 (n = 4) meningioma were irradiated from 2003 to 2018 after either STR (86%) or biopsy (14%). The median residual disease was 2.4 cm (range: 1.2-10.5), with a median bi-dimensional product of 3.6 cm2 (range: 1.3-57.4). EBRT included intensity-modulated radiation therapy (IMRT, 68%), proton beam therapy (PBT, 18%), or a combination of both (14%), to a median dose of 59.4 Gy (range: 50.4-63). After a median follow-up of 29 months, the 3-year LC, PFS and OS rates were 60%, 47%, and 68%, respectively. Response rate was 21% (6 partial responses), but 61% had any degree of radiographic shrinkage. The median time to partial response was 11 months (range: 5-13). Grade 2 (p = .049), smaller residual disease as estimated by bi-dimensional product (p = .027), and any radiographic shrinkage (p = .035) were associated with improved LC, but not radiation dose, use of PBT, nor objective response by the MacDonald criteria. Symptomatic radionecrosis occurred in 14% of cases. Clinical outcomes of incompletely resected grade 2-3 meningiomas remain limited despite high-dose EBRT; thus, additional novel therapy to combine with EBRT should be investigated. Radiologic response using the MacDonald criteria may not predict for LC and may not be the optimal criteria for response evaluation.

Intraoperative radiation therapy (IORT) for soft tissue sarcoma – ESTRO IORT Task Force/ACROP recommendations

PurposeTo describe guidelines for the use of intraoperative radiation therapy (IORT) in the treatment of soft-tissue sarcomas (STS). MethodsA panel of experts in the field performed a systematic literature review, supplemented their clinical experience and developed recommendations for the use of IORT in the treatment of STS. ResultsBased on the evidence from the systematic literature review and the clinical experience of the panel members, recommendations regarding patient selection, incorporation into multimodal treatment concepts and the IORT procedure itself are made. The rationale for IORT in extremity and retroperitoneal STS is summarized and results of the major series in terms of patient and treatment characteristics, oncological outcome and toxicity are presented. We define surgical factors, volumes for irradiation, technical requirements, dose prescription, recording and reporting, treatment delivery and care during the course of IORT covering the main IORT techniques used for the treatment of STS.In extremity STS, evidence originates from a few small prospective and mainly from retrospective single centre studies. Based on those reports, IORT containing-approaches result in very high local control rates with low rates of acute and late toxicity.In retroperitoneal sarcomas, evidence is derived from one prospective randomized trial, a few prospective and a large number of retrospective studies. The randomized trial compared IORT combined with moderate doses of postoperative external-beam radiation therapy (EBRT) to high-dose postoperative EBRT alone after gross total resection, clearly favouring the IORT-containing approach. These results have been confirmed by the prospective and retrospective studies, which similarly showed high local control rates with acceptable toxicity, mainly favouring combinations of preoperative EBRT and IORT. ConclusionsIORT-containing approaches result in high rates of local control with low to acceptable toxicity rates. Based on the available evidence, we made recommendations for the use of IORT in STS. Clinicians and researchers are encouraged to use these guidelines in clinical routine as well as in the design of future trials.

External Validation of Radiation-Induced Dyspnea Models on Esophageal Cancer Radiotherapy Patients.

Purpose: Radiation-induced lung disease (RILD), defined as dyspnea in this study, is a risk for patients receiving high-dose thoracic irradiation. This study is a TRIPOD (Transparent Reporting of A Multivariable Prediction Model for Individual Prognosis or Diagnosis) Type 4 validation of previously-published dyspnea models via secondary analysis of esophageal cancer SCOPE1 trial data. We quantify the predictive performance of these two models for predicting the maximal dyspnea grade ≥ 2 within 6 months after the end of high-dose chemo-radiotherapy for primary esophageal cancer.Materials and methods: We tested the performance of two previously published dyspnea risk models using baseline, treatment and follow-up data on 258 esophageal cancer patients in the UK enrolled into the SCOPE1 multi-center trial. The tested models were developed from lung cancer patients treated at MAASTRO Clinic (The Netherlands) from the period 2002 to 2011. The adverse event of interest was dyspnea ≥ Grade 2 (CTCAE v3) within 6 months after the end of radiotherapy. As some variables were missing randomly and cannot be imputed, 212 patients in the SCOPE1 were used for validation of model 1 and 255 patients were used for validation of model 2. The model parameter Forced Expiratory Volume in 1 s (FEV1), as a predictor to both validated models, was imputed using the WHO performance status. External validation was performed using an automated, decentralized approach, without exchange of individual patient data.Results: Out of 258 patients with esophageal cancer in SCOPE1 trial data, 38 patients (14.7%) developed radiation-induced dyspnea (≥ Grade 2) within 6 months after chemo-radiotherapy. The discrimination performance of the models in esophageal cancer patients treated with high-dose external beam radiotherapy was moderate, area under curve (AUC) of 0.68 (95% CI 0.55–0.76) and 0.70 (95% CI 0.58–0.77), respectively. The curves and AUCs derived by distributed learning were identical to the results from validation on a local host.Conclusion: We have externally validated previously published dyspnea models using an esophageal cancer dataset. FEV1 that is not routinely measured for esophageal cancer was imputed using WHO performance status. Prediction performance was not statistically different from previous training and validation sets. Risk estimates were dominated by WHO score in Model 1 and baseline dyspnea in Model 2. The distributed learning approach gave the same answer as local processing, and could be performed without accessing a validation site's individual patients-level data.

Modified Immune Cells (Autologous Dendritic Cells) and a Vaccine (Prevnar) After High-Dose External Beam Radiation Therapy in Treating Patients With Unresectable Liver Cancer

Modified Immune Cells (Autologous Dendritic Cells) and a Vaccine (Prevnar) After High-Dose External Beam Radiation Therapy in Treating Patients With Unresectable Liver Cancer

Rectum-spacer related acute toxicity \u2013 endoscopy results of 403 prostate cancer patients after implantation of gel or balloon spacers

BackgroundRectal spacers are used to limit dose to the anterior rectal wall in high dose external beam radiation therapy of the prostate and have been shown to reduce radiation induced toxicity. Here we report the complication rate and toxicity of the implantation procedure in a large cohort of patients who have either received a gel- or balloon-type spacer.MethodsIn total, 403 patients received rectal spacing, 264 with balloon, 139 with gel. Allocation was non-randomized. Two hundred seventy-six patients were treated with normofractionated regimen, the remaining 125 patients in moderate hypofractionation. Spacer related acute and late rectal toxicity was prospectively assessed by endoscopy using a mucosa scoring system (Vienna Rectoscopy Score) as well as CTCAE V.4. For the balloon subgroup, position and rotation of balloon spacers were additionally correlated to incidence and grade of rectal reactions in a post-hoc analysis of post-implant planning MRIs.ResultsOverall rectal toxicity was very low with average VRS scores of 0.06 at the day after implantation, 0.10 at the end of RT, 0.31 at 6 months and 0.42 at 12 months follow up. Acute Grade 3 toxicity (rectum perforation and urethral damage) directly related to the implantation procedure occurred in 1.49% (n = 6) and was seen exclusively in patients who had received the spacer balloon. Analysis of post implant MR imaging did not identify abnormal or mal-rotated positions of this spacer to be a predictive factors for the occurrence of spacer related G3 toxicities.ConclusionsSpacer technology is an effective means to minimize dose to the anterior rectal wall. However, the benefits in terms of dose sparing need to be weighed against the low, but possible risks of complications such as rectum perforation.

The role of external beam radiotherapy for hepatocellular carcinoma patients with lymph node metastasis: a meta-analysis of observational studies.

PurposeLymph node metastasis of hepatocellular carcinoma is categorized as advanced in Barcelona Clinic of Liver Cancer staging, and sorafenib is a sole treatment recommended. However, appliance of local treatment including external beam radiotherapy (EBRT) has not been uncommon. We performed a meta-analysis and systemically reviewed current literature to evaluate the efficacy and safety of EBRT.MethodsPubMed, Medline, Cochrane library, and Embase were systemically searched until December 17, 2017. The primary endpoint of analyses was response rate (RR), and 1-year overall survival and complication rates of grade ≥3 were secondary endpoints. Complications were primarily assessed descriptively.ResultsA total of 8 studies comprising 521 patients were included. The pooled RR was 73.1% (95% confidence interval [CI]: 63.6–80.9), and high-dose EBRT groups had better RR than the low-dose group (82.2% [95% CI: 74.4–88.1] vs 51.1% [95% CI: 40.3–61.7]; P=0.001]. The pooled 1-year overall survival rate was 41.0% (95% CI: 32.9–49.6). Six studies assessed the survival benefit according to RR, and 5 (83.3%) of these 6 studies reported statistically significant survival benefit. The most common grade ≥3 toxicities were thrombocytopenia and gastrointestinal complication, with pooled rates of 3.4% (95% CI: 1.2–9.5) and 3.5% (95% CI:1.7–7.2), respectively.ConclusionEBRT showed a pooled RR of 73.1% and was safely performed. EBRT might palliate symptoms through tumor reductions and improve survival. Use of sorafenib combined or sequentially with EBRT can be recommended rather than monotherapy.

Thoracic reirradiation with SBRT for residual/recurrent and new primary NSCLC within or immediately adjacent to a prior high-dose radiation field

PurposeLocal failure following concurrent chemoradiation and in-lobe failures following stereotactic body radiation therapy (SBRT) are common. We evaluated our institutional experience using SBRT as salvage in this setting. Methods and materialsSeventy-two patients were reirradiated with SBRT for residual, locally recurrent, or new primary non-small cell lung cancer within or adjacent to a high-dose external beam radiation therapy or SBRT field. Kaplan-Meier analysis with log-rank test were used to estimate endpoints and differentiate cohorts. ResultsMedian follow-up was 17.9 months. Patients had residual or recurrent disease (54.2%); 45.8% had new lung primaries. Median reirradiated T size was 2.5 cm (range, 0.8-7.8 cm). Median pre-retreatment maximum standardized uptake value (SUVmax) was 7.15 (range, 1.2-37.6). The most common SBRT reirradiation regimen was 48 Gy in 4 fractions (range, 17-60 Gy in 1-5 fractions). Median progression-free survival was 15.2 months, and median overall survival was 20.8 months. Two-year local failure was 21.6%. Patients with SUVmax at reirradiation <7.0 had a 2-year local control of 93.1% versus 61.1% above the median (P < .001). The 2-year rate of distant metastases was 10.4% versus 54.1% in patients treated for a new primary versus residual or recurrent disease (P < .001). Median progression-free survival was 31.9 months versus 8.4 months, respectively (P = .037). Median survival of patients treated for new primary was 25.2 months versus 16.2 months with residual or recurrent disease (P = .049), and median survival for patients with reirradiation SUVmax below the median was 42.0 months versus 9.8 months above the median (P < .001). Acute any-grade toxicity was seen in 29.2% of patients, acute grade 3 toxicity in 11.1%, and late grade 3 toxicity in 1.4% with no treatment-related deaths. ConclusionsSBRT appears to be a safe and effective means of salvaging recurrent, residual, or new primary NSCLC in or adjacent to a previous high-dose radiation field.

Case: Testicular oligometastasis from prostate cancer - Report of rare isolated recurrence after radiotherapy and intermittent androgen-deprivation therapy.

Testicular oligometastasis secondary to prostate cancer is rare. We present a case where a patient with locally advanced prostate cancer was treated with high-dose external beam radiotherapy and two years of androgen-deprivation therapy, followed by intermittent androgen suppression. Three and a half years after initial diagnosis, he was found to have a painless testicular mass. Orchiectomy was performed and histopathology demonstrated metastatic prostatic adenocarcinoma. He remains in clinical remission on intermittent androgen suppression eight years following initial treatment, and over four years after presentation with testicular metastasis.

Corneal complications after orbital radiotherapy for primary epithelial malignancies of the lacrimal gland

PurposeTo review the long-term corneal complications after high-dose external beam orbital radiotherapy given to patients for lacrimal gland carcinomas. The impact of prophylactic measures to improve long-term ocular surface health...

Definitive Radiotherapy for Primary Squamous Cell Carcinoma of the Vagina: Are High-Dose External Beam Radiotherapy and High-Dose-Rate Brachytherapy Boost the Best Treatment? Experience of Two Italian Institutes

Introduction: We assessed the clinical outcome and survival of 70 patients with primary vaginal squamous cell carcinoma undergoing radiotherapy (RT) at the Divisions of Radiotherapy, University of Pisa and ASST Cremona between January 1995 and June 2016. Methods: 58 patients received external beam RT (EBRT) to the entire vagina, para-vaginal area and pelvic nodes (total dose: 45-50.4 Gy). 29 patients (41.4%) received concomitant weekly cisplatin 40 mg/m². 35 patients received an additional (15-36 Gy) high-dose-rate (HDR) brachytherapy (BT) boost and 13 received an additional (9-25 Gy) EBRT boost to the primary tumor site. 12 women exclusively received HDR-BT up to a total dose of (30-58 Gy). Results: Median overall survival (OS) was 85 months. A total RT dose of > 60 Gy was significantly associated with a better OS (p = 0.015). There was a trend for a better OS for patients aged < 70 years and for those undergoing EBRT to the entire vagina and pelvis plus BT boost. The most common grade 1-2 acute toxicities were diarrhea (24.1%) and cystitis (20.7%); grade 3 cystitis only occurred in 2 patients (3.4%). Conclusions: EBRT followed by BT boost seems to be the best treatment for vaginal carcinoma. The total dose of RT should be > 60 Gy.

Heterogeneity in high-risk prostate cancer treated with high-dose radiation therapy and androgen deprivation therapy

BackgroundOur aim was to assess the heterogeneity of high-risk (HR) prostate cancer managed with high-dose external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT).MethodsWe identified 547 patients who were treated with modern EBRT from 1997 to 2013, of whom 98% received ADT. We analyzed biochemical relapse-free survival (bRFS) and distant metastases-free survival (DMFS).ResultsMedian EBRT dose was 74 Gy, and median ADT duration was 8 months. At 5 years, the DMFS was 85%. On multivariate analysis, significant predictors of shorter bRFS were biopsy Gleason score (bGS) of 8 to 10, higher prostate-specific antigen (PSA) level, shorter duration of ADT and lower radiation dose while predictors of shorter DMFS were bGS of 8 to 10, higher PSA level, and lower radiation dose. We identified an unfavorable high-risk (UHR) group of with 2–3 HR factors based on 2015 National Comprehensive Cancer Network (NCCN) criteria and a favorable high-risk (FHR) group, with 1 HR feature. Comparing very-HR prostate cancer, UHR & FHR, 5 year bRFS rates were 58.2%, 66.2%, and 69.2%, and 5 year DMFS rates were 78.4%, 81.2%, and 88.0%.ConclusionPatients with multiple HR factors have worse outcome than patients with 1 HR factor. Future studies should account for this heterogeneity in HR prostate cancer.

Clinical registry of dental outcomes in head and neck cancer patients (OraRad): rationale, methods, and recruitment considerations

BackgroundMost head and neck (H&N) cancer patients receive high-dose external beam radiation therapy (RT), often in combination with surgery and/or chemotherapy. Unfortunately, high-dose RT has significant adverse effects on the oral and maxillofacial tissues, some of which persist for the life of the patient. However, dental management of these patients is based largely on individual and expert opinion, as few studies have followed patients prospectively to determine factors that predict adverse oral sequelae. In addition, many previous studies were conducted before wide-spread adoption of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy. The objective of this multi-center study is to systematically evaluate the oral health of subjects for 2 years after commencement of RT, with the goal of identifying risk factors that predict adverse oral outcomes post-RT.MethodsThis is a prospective multi-center longitudinal cohort study of H&N cancer patients who receive high-dose RT with curative intent. Planned enrollment is 756 subjects at 6 primary clinical sites (and their affiliated sites) in the USA. A baseline visit is conducted prior to the beginning of RT. Follow-up visits are conducted at 6, 12, 18 and 24 months from the start of RT. The primary outcome measure is the 2-year rate of tooth loss in patients who have received at least one session of external beam RT for H&N cancer. Secondary outcome measures include the incidence of exposed intraoral bone; incidence of post-extraction complications; change in Decayed Missing and Filled Surfaces (DMFS); change in periodontal measures; change in stimulated whole salivary flow rates; change in mouth opening; topical fluoride utilization; chronic oral mucositis incidence; changes in RT-specific quality of life measures; and change in oral pain scores.DiscussionThis study will contribute to a better understanding of the dental complications experienced by these patients. It will also enable identification of risk factors associated with adverse outcomes such as tooth loss and osteoradionecrosis. These findings will support the development of evidence-based guidelines and inform the planning of future interventional studies, with the goal of advancing improvements in patient care and outcomes.Trial registrationClinicalTrials.gov Identifier NCT02057510, registered 5 February 2014.

Palliative Radiotherapy and Hormonal Deprivation for Prostate Cancer Induced Urinary Obstruction at a Sub-Saharan Tertiary Hospital

The occurrence of bladder outlet obstruction (BOO) in men with prostate cancer is common. Although relieving the obstruction may not change prognosis, it is highly valued by patients and is generally associated with improvement in general functioning and wellbeing in the short-term. The aim of this study was to assess the efficacy of high-dose external beam radiation therapy (EBRT) combined with bilateral subcapsular orchidectomy (BSO) to relieve BOO due to prostate cancer. A retrospective study design was employed and conducted at the Mulago National Referral Hospital. Records of all patients with high-risk prostate cancer who presented with urinary obstructive symptoms and treated with the BSO and EBRT were retrieved. The study variables were age, clinical stage, and pathological Gleason score. The endpoint of the study was for patients to be able to pass urine after removing the urethral catheter, analysed as follows: complete failure to pass urine; partial emptying with a post-void volume &gt;100 mL, and passing urine with complete emptying and a post-void volume &lt;100 mL. In total, 46 patients were analysed in the period of January 2011–December 2012. Mean age was 71 years (range: 63–93). Eight patients failed to pass urine, while six passed urine incompletely (partial emptying). Thirty-two passed urine with a good stream and emptied the bladder completely. The success rate was 32/46 (70%). All patients had T3 and T4 stage disease with Gleason scores &gt;8. In conclusion, orchidectomy combined with EBRT was found to be an effective and feasible option for relieving BOO due to prostate cancer.

Rhabdomyosarcoma of the External Ear Canal Treated with Brachytherapy

Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. RMS of the ear usually involves the middle ear cavity. Treatment usually involves surgery, multi drug chemotherapy regimen, and high dose external beam radiotherapy (EBRT). We present a case of a 17-month-old Caucasian female with an unusual presentation of RMS localized to her external ear canal only, which was initially believed to be an otitis media. Treatment consisted of a regimen involving brachytherapy as the radiation modality rather than EBRT. The goal of brachytherapy use is to decrease morbidity associated with radiation of the head and vital organs in developing children.