Combined External Beam Radiotherapy Research Articles

Assessing cumulative dose distributions in combined external beam radiotherapy and intracavitary brachytherapy for cervical cancer by treatment planning based on deformable image registration.

BackgroundThis study aimed to validate the feasibility of deformable image registration (DIR) in assessing the cumulative dose distributions in combined external beam radiotherapy (EBRT) and intracavitary brachytherapy (ICBT) for cervical cancer.MethodsThis retrospective study included 23 patients with stage IIB disease treated with combined EBRT to the whole pelvis (50.4 Gy in 28 fractions) using an intensity-modulated radiotherapy technique with 6-MV X-ray, followed by three-dimensional (3D) ICBT (28 Gy in 4 fractions). Tumor gross target volume at diagnosis (GTV-Tinit), tumor gross target volume before brachytherapy, high-risk clinical target volume (HR-CTV), intermediate-risk clinical target volume (IR-CTV), and parametrium and organs at risk were recontoured on computed tomography images of EBRT and ICBT, respectively. The dose-volume parameters were also determined. The DIR results were reviewed using MIM Maestro (Reg Review) and modified by function (Reg Refine). To evaluate the accuracy of DIR, DIR-based cumulative dose-volume histogram (DVH) parameters and simple DVH parameter addition were compared using Wilcoxon rank-sum tests.ResultsThe cumulative dose distributions of EBRT and four ICBT sessions were successfully illustrated using DIR. The mean tumor diameters were 68.35 cm3 at diagnosis and 29.63 cm3 at ICBT initiation. The mean tumor regression was 56.6%. The median minimum dose covering 90% (D90) of HR-CTV, GTV-Tinit, IR-CTV, and parametrium were 69.58±4.94, 68.81±7.98, 59.28±3.78, and 60.97±1.1 Gyα/β=10, respectively, for DIR and 69.11±5.68, 68.49±8.62, 58.89±3.59, and 61±1.49 Gyα/β=10, respectively, with conventional simple DVH parameter addition.No statistically significant differences in dosimetric parameters were observed between the two methods.ConclusionsAlthough there were limitations in the DIR accuracy, DIR-based dose accumulation was significantly beneficial in visually showing the cumulative dose distribution in the target area to clinicians in combined radiotherapy for cervical cancer in routine clinical practice.

Outcome of Definitive Treatments in Primary Vaginal Cancer Patients: An Institutional Review

To review the treatment outcome in primary vaginal cancer patients who underwent definitive treatment at our institution. A total of 43 patients with histologically proven primary vaginal cancer, who were treated between January 2005 to December 2015, were identified. All were treated with definitive radiotherapy with or without concurrent chemotherapy. Radiotherapy was delivered as a combination of external beam radiotherapy and brachytherapy to a minimum dose of 60 Gy. Four patients were FIGO stage I, 13 were stage II, 23 stage III patients and three patients were stage IVA. The median age was 60 years (range 42–76). The median follow-up was 29 months with a range of 3 to 70 months. The different variables looked into like the histology, lower third of vagina involvement and prior hysterectomy did not show any difference in survival. Addition of concurrent chemotherapy was the only factor which showed a trend towards better survival with a p value of 0.09. Even in the subset of patients with prior hysterectomy, those who received definitive treatment with concurrent chemo-radiotherapy had a better two-year progression-free survival than those who received radiotherapy alone (57.4% Vs 10.5%). A combination of EBRT and brachytherapy with concurrent chemotherapy is a reasonable option in the management of primary vaginal cancer. Further optimization of the dose and techniques of radiotherapy are warranted.

Relevance of the combination of external beam radiotherapy with the hypoxia-activated prodrug ICF05016 in an experimental model of extraskeletal myxoid chondrosarcoma.

Currently, there is no gold standard treatment for Extraskeletal Myxoid Chondrosarcomas (EMC) making wide margin surgical resection the most effective alternative treatment. Nevertheless, in previous preclinical studies our lab demonstrated the potential of the hypoxia-activated prodrug (HAP) ICF05016 on EMC murine model inoculated with the H-EMC-SS human cell line. The aim of this study was to assess, in vivo, the relevance of the combination of this HAP with External Beam Radiotherapy (EBR). Firstly EMC-bearing mice were treated with 6Gy or 12Gy of EBR (single 6 MV photon). Then for combination of HAP and EBR, animals received 6 doses of ICF05016 (46.8μmol/kg, intravenously) at 4-day intervals, with 6Gy EBR performed 24h after the 3rd dose of HAP. Animals were monitored throughout the study for clinical observations (tumour growth, side effects) and survival studies were performed. From tumour samples, PCNA, Ki-67 and p21 expressions were used as markers of proliferation and cell cycle arrest. Statistical significances were determined using Kruskall-Wallis and log rank tests. The radiosensitivity of the EMC model was demonstrated at 12Gy with significant inhibition of tumour growth. Then, the HAP strategy potentiated EBR efficacy at a lower dose (6Gy) by improving survival without generating side effects. Thus, results of this study showed the potential interest of ICF05016 for the combination with EBR in the management of EMC.

Definitive Radiation Therapy for Medically Inoperable Endometrial Cancer

The standard of care for patients with endometrial cancer typically involves upfront surgery. External beam radiotherapy, brachytherapy, and/or chemotherapy are implemented in the adjuvant setting based on individual risk factors. In the subset of women who are unable to receive surgery due to medical comorbidities or tumor-related factors, external beam radiation and/or uterine brachytherapy can be employed in the definitive setting. To evaluate the clinical outcomes from definitive radiation therapy in women with newly diagnosed, medically inoperable, endometrial cancer. We used an institutional endometrial cancer database to identify medically inoperable patients who received definitive radiation therapy from 1999-2018. Kaplan-Meier method was used to calculate overall survival, cause-specific survival, and locoregional recurrence free survival. Cox regression analysis was used to assess variables associated with these outcomes. Forty-four patients were identified, with a median follow up of 29.1 months. Median age was 68 years (R: 40-90) and the median body mass index (BMI) was 43 (R:23-88). Ten patients (22.7%) had FIGO grade 3 disease. One patient received external beam radiation to the pelvis alone, twenty-seven patients underwent brachytherapy alone, and sixteen patients received combined external beam radiation to the pelvis followed by consolidative uterine brachytherapy. Chemotherapy was delivered in the neoadjuvant setting in two patients, adjuvant in one patient, and concurrently in two patients. 55% of patients had PET/CT and/or MRI based treatment planning. Four patients were unable to complete their intended treatment course due to exacerbation of medical comorbidities (2), progression of disease during treatment (1), or uterine perforation (1). Locoregional recurrence free survival was 92% (95% C.I. 83.7-100%) at 2 years. Cause-specific survival and overall survival were 79.3% (95% C.I. 65.8-95.7%) and 62% (95% C.I. 48.8-78.7%) respectively at 2 years. On univariate analysis, Grade 3 disease, age, and the presence of lymphadenopathy were associated with decreased overall survival, while surprisingly, BMI was associated with improved OS. KPS less than 80, radiotherapy technique, and smoking status were not associated with OS. On multivariate analysis, only the presence of lymphadenopathy remained significant. No variables were significantly associated with locoregional recurrence. There were no acute grade 3 toxicities observed in this cohort. Grade 3 toxicity was seen in 7.8% of patients with sufficient long term follow up. Definitive radiation therapy for endometrial cancer in medically inoperable patients is associated with excellent locoregional control and cause-specific survival. Cause-specific survival was considerably longer than overall survival in this cohort, suggesting that these patients frequently succumb to other medical conditions.

Second primary tumors in retinoblastoma survivors: a study of 7 Asian Indian patients.

To assess the incidence, types, and outcomes of second primary tumors (SPT) in cases of retinoblastoma (RB) from a referral Tertiary eye care center METHODS: Retrospective chart review of 7 cases RESULTS: All 7 (100%) cases had bilateral RB at presentation. The mean age at diagnosis of RB was 16months (median 7months; range 5-72months). Treatment of RB with intravenous chemotherapy was noted in 3 (43%) patients, 1 (14%) patient had received external beam radiotherapy (EBRT) to the orbit, 1 (14%) patient had received a combination of chemotherapy and orbital EBRT, while 4 (57%) patients had undergone primary enucleation of the worse eye and focal treatment of the better eye. The mean age at detection of SPT was 15years (median 8years; range 6-46years). The mean time interval between diagnosis of RB and SPT was 13years (median 7years; range 1-41years). The SPT's included osteosarcoma of long bone (n = 2), eyelid sebaceous gland carcinoma (n = 2), ventricular ependymoma (n = 1), orbital neuroblastoma (n = 1), and acute lymphoblastic leukemia (n = 1). All patients received treatment for the SPT with either surgical excision (n = 2), intravenous chemotherapy (n = 1), or a combination of surgery/chemotherapy/radiotherapy (n = 4). Over a mean follow-up period of 8years (median 8years; range 4-11years), one (14%) patient died, while other 6 (86%) patients are alive and well. Though the incidence of SPT's in cases of RB is rare, life-long follow-up is mandatory in at-risk patients.

Overall survival comparison between androgen deprivation therapy (ADT) plus external beam radiation therapy (EBRT) vs ADT plus EBRT with brachytherapy boost in clinically node-positive prostate cancer

PurposeOptimal therapy for clinically node-positive, nonmetastatic (cN1) prostate cancer (PC) patients remains controversial, ranging from aggressive local therapy to palliative systematic therapy alone. Despite guideline support, it is unclear if a brachytherapy (BT) boost should be considered for cN1 patients as these patients were excluded from randomized trials establishing its benefit. Herein, we compare definitive radiation therapy (RT) with or without a BT boost in cN1 PC. Methods and materialsThe National Cancer Database was used to identify men with cN1 PC treated with definitive RT and concomitant androgen deprivation therapy between 2004 and 2013. Overall survival (OS) was compared between those who received external beam RT (EBRT) or combination EBRT plus BT boost (EBRT + BT) using Kaplan–Meier with propensity score matching and Cox proportional hazards. ResultsWith a median followup of 48.5 months, 1,650 patients were eligible for this analysis, 103 (6.2%) of whom received EBRT + BT. Younger age, no medical comorbidities, and Gleason score of six were associated with higher likelihood of receiving EBRT + BT over EBRT alone. The mean (median) OS for EBRT and EBRT + BT was 99.0 (110.6) months vs 109.2 (not reached) months, respectively (p = 0.048). However, no significance difference in OS was observed between the groups after propensity score matching. On multivariable analysis, EBRT + BT was not significantly associated with improved OS (adjusted HR 0.67, 95% CI, 0.41–1.07, p = 0.098). ConclusionsIn this retrospective, observational study of patients with cN1 PC treated with definitive RT and concomitant androgen deprivation therapy, EBRT + BT had an unadjusted improvement in OS compared with EBRT alone that lost statistical significance after multivariable adjustment and propensity score matching.

Perioperative high-dose-rate brachytherapy (PoHDR) in the multidisciplinary management of adult soft tissue sarcomas: a realistic alternative for a moderate radiotherapy dose escalation

Conservative surgery in combination with local radiation therapy is considered a standard approach for soft tissue sarcomas (STS) leading to high local control rates and widely replacing the need for amputations. A close relationship exists between total radiation dose and local control probability. Combination of external beam radiotherapy and perioperative brachytherapy represents a moderate dose escalation that could contribute to improve local control. From May 2015 to October 2018, 23 patients with histologically proven STS of various locations were prospectively entered into a data registry of perioperative HDR brachytherapy (PoBT) combined with external beam radiotherapy (EBRT). Multidisciplinary treatment comprised wide surgical excision, PoBT (16.5 Gy delivered in 3 fractions of 5.5 Gy twice daily with a gap time of at least 6 h between fractions), and EBRT delivered either pre- or postoperatively (median dose 47 Gy, range 40–57.5 Gy) up to a total accumulated radiotherapy equivalent dose for tumor of 69.5 to 86.5 Gy (median, 76.1 Gy), representing a moderate total dose escalation over the 66 Gy traditionally used. With a median follow-up of 13.4 months (range, 1–35.4 months), 22 patients (96%) remain alive without evidence of local or distant recurrence, 1 patient (4%) is alive with local relapse, and no patient has died because of tumor progression. Treatment-related adverse effects were mild or moderate. No cases of grades 4–5 late toxicity have been observed during the follow-up period. HDR PoBT is safe, feasible, and well tolerated and allows for a moderate radiation dose escalation with acceptable rates of tumor control. Further follow-up is necessary to confirm impact on final outcomes.

Outcomes and toxicity after salvage radiotherapy for vaginal relapse of endometrial cancer

ObjectivesStudies of salvage radiotherapy in locally recurrent endometrial cancer remain limited. The aim of this study was to evaluate the efficacy of salvage radiotherapy for vaginal relapse of endometrial cancer...

Acute patient-reported bowel quality of life and rectal bleeding with the combination of prostate external beam radiation, low-dose-rate brachytherapy boost, and SpaceOAR

PurposeThis study evaluates acute patient-reported bowel quality of life (QOL) and rectal bleeding in prostate cancer patients treated with combination external beam radiation (EBRT), low-dose-rate brachytherapy (LDR-BT), and SpaceOAR. Materials and MethodsA retrospective review of prostate cancer patients treated with EBRT (45 Gy), cesium-131 LDR-BT (85 Gy), and SpaceOAR was conducted. Patient-reported acute (≤3 months after LDR-BT) bowel QOL and rectal bleeding was analyzed from Expanded Prostate Cancer Index Composite (EPIC) questionnaires. Five-point changes in mean bowel QOL scores were considered clinically significant. Clinically significant rectal bleeding was bleeding occurring more than “rarely” (“about half the time,” “usually,” or “always”), and clinically significant bleeding bother was considering bleeding a “small, moderate, or big problem.” Outcomes were analyzed using descriptive statistics and paired t-tests. Results69 patients were identified. Bowel summary, function, and bother scores clinically and significantly decreased 2 weeks after LDR-BT (79.9 ± 15.6, 80.5 ± 15.4, and 79.4 ± 18.1, respectively) compared with pre-EBRT scores (92.3 ± 9.1, 93.3 ± 9.0, and 92.6 ± 11.9, respectively) and pre-LDR-BT scores (91.1 ± 11.0, 91.6 ± 9.8, and 90.6 ± 13.3, respectively), but returned to clinical and statistical baseline pre-EBRT values at 3 months (88.7 ± 12.4, 88.8 ± 11.1, and 88.7 ± 14.5, respectively). The 3-month cumulative incidence of clinically significant rectal bleeding and bleeding bother was 4.35% and 2.90%, respectively. ConclusionsWith combination EBRT, LDR-BT, and SpaceOAR, bowel QOL returned to the baseline 3 months after LDR-BT. Clinically significant rectal bleeding was <5%. Further followup will confirm if low acute rectal toxicity translates to reduced late toxicity.

Cesium-131 prostate brachytherapy: A single institutional long-term experience

AimsTo report on the PSA outcomes in men undergoing prostate seed implant (PSI) with Cesium-131 at a single institution. Materials and MethodsAll patients who underwent prostate brachytherapy with Cesium-131 (131Cs) at our institution and had the potential for at least 24 months of follow up were included in this study. Results are reported for the by NCCN risk group (low, low/high-intermediate, and high), as well as by treatment received (monotherapy, combination external beam radiation + PSI, or trimodal therapy with androgen deprivation). The Phoenix definition (absolute nadir plus 2 ng/mL) was used to define biochemical freedom from disease (BFD). ResultsEight hundred and six men have undergone prostate brachytherapy with Cesium-131 at our institution, and 669 men were included in analysis. Median follow up was 60.0 months (range: 0–144 months). According to NCCN risk categories, 29.9% were low-, 55.6% intermediate-, and 14.5% high-risk. Using the Phoenix criteria, 5/10-year BFD was 97.1/95.3% for patients in the low-risk category, 94.0/90.1% for patients in the intermediate-risk category, and 86.2/56.6% for patients in the high-risk category. PSA ≤0.2 ng/dL at 4 years was predictive of 10 year biochemical control: 96.3% vs 70.4%, p < 0.001. ConclusionsThe present study demonstrates that prostate brachytherapy with 131Cs achieves excellent long-term biochemical control.

MP35-18 DORSAL ONLAY URETHROPLASTY FOR RADIATION-INDUCED URETHRAL STENOSIS; A MULTI-INSTITUTIONAL RETROSPECTIVE REVIEW

You have accessJournal of UrologyTrauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I (MP35)1 Apr 2020MP35-18 DORSAL ONLAY URETHROPLASTY FOR RADIATION-INDUCED URETHRAL STENOSIS; A MULTI-INSTITUTIONAL RETROSPECTIVE REVIEW Michael Hughes*, Connor Policastro, Francisco Martins, Jay Simhan, Nicolaas Lumen, Krishnan Venkatesan, Javier Angulo, Shubham Gupta, Paul Rusilko, Erick Alejandro Ramírez Pérez, Alan Quach, Michael Altwell, Kirk Redger, Brian Flynn, Stephen Blakely, and Dmitriy Nikolavsky Michael Hughes*Michael Hughes* More articles by this author , Connor PolicastroConnor Policastro More articles by this author , Francisco MartinsFrancisco Martins More articles by this author , Jay SimhanJay Simhan More articles by this author , Nicolaas LumenNicolaas Lumen More articles by this author , Krishnan VenkatesanKrishnan Venkatesan More articles by this author , Javier AnguloJavier Angulo More articles by this author , Shubham GuptaShubham Gupta More articles by this author , Paul RusilkoPaul Rusilko More articles by this author , Erick Alejandro Ramírez PérezErick Alejandro Ramírez Pérez More articles by this author , Alan QuachAlan Quach More articles by this author , Michael AltwellMichael Altwell More articles by this author , Kirk RedgerKirk Redger More articles by this author , Brian FlynnBrian Flynn More articles by this author , Stephen BlakelyStephen Blakely More articles by this author , and Dmitriy NikolavskyDmitriy Nikolavsky More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000879.018AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Management of recurrent post-radiation urethral stenosis is notoriously difficult due to poorer success rates and the risk of de-novo stress urinary incontinence (SUI) following reconstruction. Although many prior reports describe outcomes of anastomotic or ventral buccal mucosa graft (BMG) augmentation techniques, dorsal onlay BMG urethroplasty (D-BMGU) has not been sufficiently assessed. Here we report patency and continence outcomes following dorsal onlay BMG urethroplasty in a large multi-institutional cohort undergoing treatment of post-radiation urethral stenosis. METHODS: Men with a history of radiotherapy for prostate cancer treatment who underwent D-BMGU for posterior urethral stenosis from 10 institutions between 2010-2019 were reviewed. Patients with a minimum of 8 months follow up were included. Preoperative patient characteristics and continence status were reviewed. Postoperative outcomes including urethroplasty failure, SUI, uroflow, post-void residual volume and PROM questionnaires were analyzed. RESULTS: Of 86 men with post-radiation stenosis treated with D-BMGU, 67 (78%, mean age 69, (range 52-85)) met inclusion criteria with a mean length of stenosis 3.9 cm (1.5-18). Radiation modalities included: 30 (45%) external beam radiotherapy (EBRT), 10 (15%) brachytherapy (BT), 9 (13%) combination EBRT and BT; and 18 EBRT and radical prostatectomy (27%). At a mean follow up of 27 months (8-88), 13 patients (19%) had urethral stenosis recurrence. Of 31 patients who had no SUI prior to surgery, only 2 men (6.4%) developed de-novo SUI following dorsal onlay urethroplasty. All 27 patients (27/67, 40%) with SUI prior to surgery remained incontinent post operatively. Of the remaining 9/67 (13.4%) men whose baseline continence status was unknown, 4/9 (44%) were incontinent post operatively. CONCLUSIONS: With comparable success rates to previously reported techniques, dorsal onlay urethroplasty with BMG is a feasible management option in patients with post-radiation posterior urethral stenosis. This non-transecting approach demonstrates diminished rates of de-novo stress incontinence compared to historically reported rates with excisional urethroplasty. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e519-e520 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael Hughes* More articles by this author Connor Policastro More articles by this author Francisco Martins More articles by this author Jay Simhan More articles by this author Nicolaas Lumen More articles by this author Krishnan Venkatesan More articles by this author Javier Angulo More articles by this author Shubham Gupta More articles by this author Paul Rusilko More articles by this author Erick Alejandro Ramírez Pérez More articles by this author Alan Quach More articles by this author Michael Altwell More articles by this author Kirk Redger More articles by this author Brian Flynn More articles by this author Stephen Blakely More articles by this author Dmitriy Nikolavsky More articles by this author Expand All Advertisement PDF downloadLoading ...

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

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

Intensity modulated radiation therapy boost in locally-advanced cervical cancer in the absence of brachytherapy

ObjectiveStandard treatment in locally-advanced cervical cancer is external beam radiotherapy concomitant with platinum-based chemotherapy, followed by brachytherapy. The goal of our study was to determine whether an intensity modulated radiation...

Long-term results of multimodal peptide receptor radionuclide therapy and fractionated external beam radiotherapy for treatment of advanced symptomatic meningioma

BackgroundThe combination of somatostatin receptor-directed peptide receptor radionuclide therapy (PRRT) in combination with external beam radiotherapy (EBRT) might prove a feasible treatment option in patients with advanced meningioma. Patients and methodsFrom May 2010 to May 2011, 10 patients with unresectable meningioma (6 × WHO grade I, 2 × WHO grade II, 2 × WHO grading not available) were treated with one cycle of PRRT followed by EBRT. Long-term toxicity and efficacy were assessed according to Common Terminology Criteria for Adverse Events version 5.0 and magnetic resonance imaging-based Response Assessment in Neuro-Oncology Working Group criteria, respectively. ResultsDuring long-term follow-up of a median of 105.0 months (range, 38.2–111.4 m), combined PRRT and EBRT was well-tolerated with no severe acute or chronic toxicity. Kidney or bone marrow function was not affected in any patient. Combination of PRRT and EBRT resulted in disease stabilization in 7 of the 10 patients with a median progression-free survival of 107.7 months (range, 47.2–111.4 m) vs. 26.2 months (range, 13.8–75.9 m) for the patients with meningioma progression. ConclusionsThe combination of PRRT and EBRT is a feasible and safe therapeutic option in meningioma patients. In this pilot cohort, the multimodality treatment demonstrated good disease stabilization.

The Impact of High-Dose-Rate Brachytherapy: Measuring Clinical Outcomes in the Primary Treatment of Cervical Cancer

PurposeRadical concurrent chemoradiotherapy with combined external beam radiotherapy (EBRT) and brachytherapy is used to treat locally advanced cervical cancer. Our institution has transitioned to high-dose-rate (HDR) intracavitary brachytherapy (ICBT) from low-dose-rate (LDR) brachytherapy in 2008, and a review was conducted on the effect of this change on patient outcomes. Methods and MaterialsA single-arm retrospective chart review was performed on locally advanced (Fédération Internationale de Gynécologie et d’Obstétrique stage IB-IVA) patients with cervical cancer treated with combined external beam radiation therapy and HDR-ICBT with curative intent between 2008 and 2014. Clinical outcomes were evaluated, and multivariate analysis was performed to identify prognostic factors. ResultsOf the 76 patients selected, median age was 47.9 years and median follow-up was 5.2 years. Thirteen patients (17.1%) developed locoregional recurrence and 23 patients (30.3%) patients developed distant recurrence. Five-year progression-free survival and overall survival were 63.7% and 69.3%, respectively. A significant survival difference was found between stages (P < .001). Multivariate analysis found nodal involvement was strongly associated with poorer survival (P = .007). ConclusionsOur experience with the transition to HDR-ICBT as part of concurrent chemoradiotherapy in treatment of locally advanced cervical cancer resulted in acceptable long-term outcomes and toxicity to that of LDR brachytherapy. Potential further improvement of treatment outcomes for patients may be possible with image guided brachytherapy and the addition of effective systemic therapy.

Adjuvant chemotherapy in endometrial cancer.

The role of adjuvant chemotherapy (CT) is controversial in endometrial carcinoma (EC). Surgery alone is usually curative for women who are at a low risk of disease recurrence. The treatment of EC following surgical staging is based on the risk of relapse, which is defined by the cancer stage at diagnosis, histology of the tumor and other prognostic factors such as grade differentiation, the presence of substantial lymphovascular invasion (LVSI), or depth of myometrial invasion (MI). External beam radiotherapy (EBRT) and/or vaginal brachytherapy (VBT) improved local control and are used as adjuvant treatment for early-stage disease. The role of adjuvant CT is controversial in early-stage EC, and there is no uniform approach to the treatment of women with stage III EC or early-staged non-endometrioid EC. Available evidence did not support the indication of adjuvant CT in stage I-II endometroid EC. In those cases at higher risk of relapse, defined as grade 3 tumors with substantial (no focal) LVSI, specifically with deep MI or cervical involvement, could be considered. Adjuvant CT should be administered to stage III EC patients. When RT is indicated (extensive lymph node involvement or deep MI), sequential treatment with RT or "sandwich" regimen may be considered rather than concurrent CRT. The patients with stage IA MI or IB USC may be offered adjuvant CT alone or in combination with VBT, whereas in stage II uterine serous carcinoma patients adding EBRT may be reasonable. Management approach for patients with stage IA without MI USC who underwent a comprehensive surgery remains controversial, and surveillance alone or CT plus VBT is an appropriate option. Early-stage clear-cell carcinoma patients might not benefit for adjuvant CT, but stage III patients might benefit from the combination of CT and EBRT. Stage I-III uterine carcinosarcoma patients might be offered adjuvant CT followed by RT or as a "sandwich" régimen.

Inter-observer and intra-observer variability in reporting vaginal dose points for cervical cancer in high-dose-rate brachytherapy.

PurposeThe ICRU 89 recommends reporting a set of vaginal dose points for cervical cancer treatments in order to quantify the goodness of implant. This vaginal dose reporting method for combined external beam radiotherapy and brachytherapy has been adopted by the EMBRACE II study protocol. Large variations in dose between patients and centers have been reported. The aim of this study was to determine possible discrepancies with consensus observers from the same institution. Therefore, the inter- and intra-observer variability were analyzed.Material and methodsFor five patients, five experienced observers reported dose at the proposed vaginal points twice. The effect of inter- and intra-observer variations on total dose was analyzed by estimating biologically equivalent dose EQD2 (α/β = 3 Gy). Coefficient of variation (CV) was used to provide a measure of data dispersion as a proportion to the mean.ResultsThe maximum inter-observer deviation among all patients and all points ranged from 0.5 Gy to 24.1 Gy in EQD2. The higher inter-observer discrepancies were found at points at 3 o’clock and at 6 o’clock, with respect to ovoids. In case of the maximum intra-observer deviation, it ranged from 0.5 Gy to 14.2 Gy, with higher deviation points at 12 o’clock and 9 o’clock, with respect to ovoids.ConclusionsThere is a need to ensure consistency in vaginal points reporting. The impact of the dosimetric inter- and intra-observer variability should also be considered when dealing with dose tolerances and limits due to the potential dose gradient.

Prostate Carcinosarcoma Developing After Combined Pelvic External Beam Radiation Therapy and Androgen Deprivation Therapy

Carcinosarcoma of the prostate is a very rare disease, which consists of carcinomatous and sarcomatous components. The prognosis of patients with prostatic carcinosarcoma is poor. An 80-year-old man who had been suffering from urinary retention and constipation with rectal pain visited a hospital. A patient with a history of combined pelvic external beam radiation therapy (EBRT) and androgen deprivation therapy (ADT) for prostate adenocarcinoma 7 years ago was diagnosed with secondary malignancy such as prostate carcinosarcoma by prostate biopsy. This is also a rare case occurring after combined EBRT and ADT for adenocarcinoma in a short interval. Then, he underwent chemotherapy for one cycle. Chemotherapy was stopped because of rapid clinical aggravation, and the patient died 5 months later. It is important to keep in mind the possibility of carcinosarcoma in the case that prostate-specific antigen maintains stable level but extent of tumor is gradually increased after EBRT or ADT. Key Words: Prostate; Carcinosarcoma; Prognosis.

Gemcitabine potentiates the anti-tumour effect of radiation on medullary thyroid cancer.

Patients with medullary thyroid cancer (MTC) are often diagnosed with spread tumour disease and the development of better systemic treatment options for these patients is important. Treatment with the radiolabelled somatostatin analogue 177Lu-octreotate is already a promising option but can be optimised. For example, combination treatment with another substance could increase the effect on tumour tissue. Gemcitabine is a nucleoside analogue that has been shown to sensitise tumour cells to radiation. The aim of this study was to investigate potentially additive or synergistic effects of combining radiation with gemcitabine for treatment of MTC. Nude mice transplanted with patient-derived MTC tumours (GOT2) were divided into groups and treated with radiation and/or gemcitabine. Radiation treatment was given as 177Lu-octreotate or external beam radiotherapy (EBRT). The volume of treated and untreated tumours was followed. The absorbed dose and amount of gemcitabine were chosen to give moderate tumour volume reduction when given as monotherapy to enable detection of increased effects from combination treatment. After follow-up, the mice were killed and tumours were immunohistochemically (IHC) analysed. Overall, the animals that received a combination of EBRT and gemcitabine showed the largest reduction in tumour volume. Monotherapy with EBRT or gemcitabine also resulted in a clear detrimental effect on tumour volume, while the animals that received 177Lu-octreotate monotherapy showed similar response as the untreated animals. The GOT2 tumour was confirmed in the IHC analyses by markers for MTC. The IHC analyses also revealed that the proliferative activity of tumour cells was similar in all tumours, but indicated that fibrotic tissue was more common after EBRT and/or gemcitabine treatment. The results indicate that an additive, or even synergistic, effect may be achieved by combining radiation with gemcitabine for treatment of MTC. Future studies should be performed to evaluate the full potential of combining 177Lu-octreotate with gemcitabine in patients.

External Beam Radiation Therapy (EBRT) and High-Dose-Rate (HDR) Brachytherapy for Intermediate and High-Risk Prostate Cancer: The Impact of EBRT Volume

Whole pelvis radiation therapy (WPRT) may improve clinical outcomes over prostate-only radiation therapy (PORT) in high-risk prostate cancer patients by sterilization of micrometastatic nodal disease, provided there is optimal control of the primary site. A prospective multicenter cohort study of eligible patients (stage ≥T2c, Gleason score ≥7 or presenting prostate-specific antigen ≥10) treated between 2009 and 2013 were enrolled in a United Kingdom national protocol delivering combined external beam radiation therapy and high-dose-rate brachytherapy. Centers elected to deliver WPRT, 46 Gy in 23 fractions or PORT 37.5 Gy in 15 fractions with 15 Gy single dose high-dose-rate brachytherapy. The primary endpoint was biochemical progression-free survival (bPFS). Secondary endpoints were overall survival, genitourinary, and gastrointestinal toxicity. This was not a randomized comparison and was subject to bias; the findings are therefore hypothesis generating, but not conclusive. Eight hundred and twelve patients were entered; 401 received WPRT and 411 received PORT. With a median follow-up of 4.7 years, 5-year bPFS rates for WPRT versus PORT arms were 89% versus 81% (P = .007) for all patients and 84% versus 77% (P = .001) for high-risk patients. Differences in bPFS remained significant after accounting for Gleason score, presenting prostate-specific antigen, T stage, and androgen deprivation therapy duration as covariates. There was no difference in overall survival. The overall post treatment toxicities across both cohorts were low with no greater than 1.5% of ≥grade 3 toxicities at any follow-up time point. WPRT increased both prevalence and cumulative incidence of acute genitourinary toxicity (P = .004) and acute gastrointestinal toxicity (P = .003). No difference in late radiation toxicity was observed. A significant improvement in 5-year bPFS was seen in intermediate and high-risk prostate cancer treated with WPRT compared with PORT in a combined external beam radiation therapy and brachytherapy schedule with no increase in late radiation toxicity.