Quality of Radiotherapy Workforce Training within the USA.

The training, competency requirements and scope of practice of professionals within a radiation oncology department vary across countries. The purpose of this review is to shed light on the current status of radiotherapy training in the USA by discussing current benchmarks for medical residency, physics residency, radiation therapy and dosimetry training programmes. Although there are notable strengths, the US radiotherapy workforce training system also faces several challenges when it comes to standardising education to develop a competent workforce that meets societal needs. Continued efforts are needed at a systemic level to improve training in areas such as brachytherapy and proton therapy, promote research involvement and develop trainees who are equipped to form a competent radiation therapy workforce.

The role of adjuvant treatment for early-stage uterine clear cell carcinomas.

BACKGROUND: Uterine clear cell carcinoma is a rare and aggressive subtype of endometrial carcinoma. Prospective clinical trials have not been feasible for this rare tumor, and data regarding the optimal adjuvant treatment regimen for early-stage uterine clear cell carcinomas is limited. Our study's objective was to determine if adjuvant chemotherapy or radiation therapy improves patients' outcomes in stage I and II uterine clear cell carcinoma. METHODS: Patients with stage I and II uterine clear cell carcinoma were identified at a single institution. All cases were reviewed by a gynecologic pathologist. Both pure and mixed non-serous uterine clear cell carcinomas were included. Primary outcomes were recurrence free survival and overall survival. RESULTS: A total of 71 patients were identified including 39 (55%) pure and 32 (45%) mixed clear cell carcinoma. Most patients were FIGO stage IA (77.5%). Most patients (n = 58, 82%) received adjuvant therapy, including 43 (61%) receiving chemotherapy, 50 (70%) receiving radiation therapy, and 35 (49%) receiving both. Recurrence free survival was not significantly different among patients receiving no or <6 cycles of chemotherapy versus patients receiving 6 cycles of chemotherapy (p = 0.39). However, median OS was significantly different among patients receiving no or <6 cycles of chemotherapy versus 6 cycles of chemotherapy (p = 0.004). On univariable analysis, 6 cycles of chemotherapy was significantly associated with improved OS (HR 0.1, 95% CI 0.01-0.07). Presence of LVSI, mutated p53, number of pelvic and para-aortic lymph nodes assessed, adjuvant chemotherapy (any number of cycles), and >2 medical co-morbidities were not significant predictors of OS on univariable analysis. On multivariable analysis, 6 cycles of adjuvant chemotherapy remained a significant predictor of improved OS (HR 0.1, 95% CI 0.01-0.8). CONCLUSIONS: In this study, administration of 6 cycles of chemotherapy appears to significantly improve OS. This finding suggests consideration of 6 cycles of adjuvant chemotherapy in patients with early-stage uterine clear cell carcinoma, however clinical trials are needed to confirm these findings.

Is Substantial Lymphovascular Space Invasion Prognostic for Clinical Outcomes in Type II Endometrial Cancer?

AIMS: Substantial lymphovascular space invasion (LVSI) compared with none or focal LVSI is predictive of lymph node involvement and worse clinical outcomes in endometrioid-type endometrial carcinoma. We aimed to quantify the incidence of substantial LVSI in type II (clear cell and serous) endometrial cancer and correlate the extent of LVSI with clinical outcomes. MATERIALS AND METHODS: A retrospective review was conducted on type II endometrial cancer patients who underwent surgical management from July 2017 to December 2019 using the three-tier LVSI scoring system. Binary logistic regression and Cox regression were used to analyse predictors of lymph node involvement or survival outcomes, respectively. The Kaplan-Meier method and Log-rank test were used to analyse differences in locoregional disease-free survival (LR-DFS), distant metastasis disease-free survival (DM-DFS) and overall survival between patients with substantial versus none/focal LVSI. RESULTS: In 79 patients with type II endometrial carcinoma, no LVSI, focal LVSI and substantial LVSI was present in 48.1%, 15.2% and 36.7% of patients, respectively. Lymph nodes were involved in 0.0% with no LVSI, 20.0% with focal LVSI and 60.0% with substantial LVSI (P < 0.001). The median follow-up was 22.2 months. In patients with none/focal versus substantial LVSI, the 2-year LR-DFS and DM-DFS rates were 91.5% versus 71.4% (P = 0.01) and 90.2% versus 63.8% (P = 0.005), respectively. On univariate analysis, myometrial invasion ≥50%, tumour size ≥3.6 cm, substantial versus none/focal LVSI, lymph node involvement and omission of adjuvant radiotherapy were significant predictors for worse LR-DFS and DM-DFS (P < 0.05). DISCUSSION: Substantial LVSI has a high incidence in type II pathology at our institution and predicts for lymph node involvement and worse clinical outcomes.

Cost-effectiveness analysis of tumor molecular classification in high-risk early-stage endometrial cancer.

PURPOSE: Tumor molecular analyses in endometrial cancer (EC) includes 4 distinct subtypes: (1) POLE-mutated, (2) mismatch repair protein (MMR) deficient, (3) p53 mutant, and (4) no specific molecular profile. Recently, a sub-analysis of PORTEC-3 demonstrated notable differences in treatment response between molecular classification (MC) groups. Cost of testing is one barrier to widespread adoption of MC. Therefore, we sought to determine the cost-effectiveness of MC in patients with stage I and II high-risk EC. METHODS: A Markov decision model was developed to compare tumor molecular classification (TMC) vs. no testing (NT). A healthcare payor's perspective and 5-year time horizon were used. Base case data were abstracted from PORTEC-3 and the molecular sub-analysis. Cost and utility data were derived from public databases, peer-reviewed literature, and expert input. Strategies were compared using the incremental cost-effectiveness ratio (ICER) with effectiveness in quality-adjusted life years (QALYs) and evaluated with a willingness-to-pay threshold of $100,000 per QALY gained. Sensitivity analyses were performed to test model robustness. RESULTS: When compared to NT, TMC was cost effective with an ICER of $25,578 per QALY gained; incremental cost was $1780 and incremental effectiveness was 0.070 QALYs. In one-way sensitivity analyses, results were most sensitive to the cost of POLE testing, but TMC remained cost-effective over all parameter ranges. CONCLUSIONS: TMC in early-stage high-risk EC is cost-effective, and the model results were robust over a range of parameters. Given that MC can be used to guide adjuvant treatment decisions, these findings support adoption of TMC into routine practice.

Utility of Prophylactic Cranial Irradiation for Limited Stage Small Cell Lung Cancer in the Modern Era with Magnetic Resonance Imaging Surveillance.

AIMS: To retrospectively analyse the impact of prophylactic cranial irradiation (PCI) on survival and intracranial progression in patients with limited stage small cell lung cancer (LS-SCLC) in the modern era of widespread magnetic resonance imaging brain screening. MATERIALS AND METHODS: Patients with LS-SCLC treated within our network between 2009 and 2020 who responded to initial therapy were stratified by receipt of PCI and stage of disease. A propensity score match analysis was carried out for stage II-III patients. Overall and neurological survival were defined as time to death and presumed death due to uncontrolled intracranial disease, respectively. Brain metastasis-free survival and symptomatic brain metastasis-free survival were defined as freedom from intracranial progression and symptomatic intracranial progression, respectively. The effect of PCI on these outcomes was assessed using Kaplan-Meier and Cox proportional hazards models. RESULTS: In total, 243 (69.6%) of 349 patients received PCI. On multivariate analysis in the propensity matched stage II-III cohort, PCI was a significant predictor of improved neurological survival (hazard ratio 0.23, 95% confidence interval 0.08-0.65; P = 0.01), brain metastasis-free survival (hazard ratio 0.25, 95% confidence interval 0.12-0.51; P < 0.01) and symptomatic brain metastasis-free survival (hazard ratio 0.21, 95% confidence interval 0.08-0.55; P < 0.01), but not improved overall survival. Two-year neurological survival estimates within the propensity matched cohort were 96.8% (95% confidence interval 87.6-99.2%) with PCI and 77.2% (95% confidence interval 63.0-86.4%) without PCI and 1- and 2-year estimates of incidence of brain metastases were 3.9% (95% confidence interval 1.3-11.7%) and 11.7% (95% confidence interval 5.6-23.5%) in the PCI group and 31.6% (95% confidence interval 22.1-43.9%) and 40.4% (95% confidence interval 29.2-54.0%) in the no PCI group, respectively. CONCLUSIONS: In the modern era of magnetic resonance imaging screening, PCI was associated with reduced incidence of intracranial progression in patients with stage II-III LS-SCLC who respond to initial therapy. This, importantly, translated to a decreased risk of neurological death within our propensity matched cohort, without significant improvement in overall survival.

Regional Control and Chemoradiotherapy Dose Response for Clinically Involved Lymph Nodes in Patients with Locally Advanced Endometrial Cancers Who are Not Candidates for Upfront Surgical Staging Extrafascial Hysterectomy.

AIMS: There are limited data in endometrial cancer for nodal control and appropriate treatment volume for non-surgically resected nodes treated with chemoradiotherapy (CRT) for patients who are not candidates for upfront extrafascial hysterectomy. MATERIALS AND METHODS: Patients (n = 105) with clinical stage ≥ II endometrial cancer who were not candidates for upfront extrafascial hysterectomy treated with preoperative CRT were retrospectively reviewed. CRT included pelvic nodes to the common iliac for node-negative disease and para-aortic nodes to the renal vessel for any node-positive disease. Involved nodes most commonly received a boost of 55 Gy in 25 fractions ± additional 4-6 Gy sequential boost for nodes >2 cm. RESULTS: Of the included 95 patients, 55 patients were node positive, with a total of 300 positive nodes. At a median follow-up of 25 months (interquartile range 9-46), the 3-year regional control was 91%. The 3-year involved nodal control rate was 96%. Involved nodal control was significantly higher in type I histology, nodes <2 cm and by radiation dose (75% for <55 Gy, 98% for 55 Gy in 25 fractions and 89% for >55 Gy, P = 0.03). The 3-year para-aortic failure rate for node negative patients treated with pelvis-only CRT was significantly higher with positron emission tomography/computed tomography (PET/CT) versus computed tomography (CT)-based staging (0% versus 20%). CONCLUSION: This is the largest study examining regional control rates of involved lymph nodes with CRT for patients who were not candidates for upfront extrafascial hysterectomy. Nodal failure was low following CRT and dose ≥55 Gy in 25 fractions seems to be adequate for involved nodes.

Early outcomes after definitive chemoradiation therapy with Vienna/Venezia hybrid high-dose rate brachytherapy applicators for cervical cancer: A single-institution experience.

PURPOSE: The Vienna and Venezia (Elekta) are hybrid intracavitary/interstitial brachytherapy (BT) applicators for cervical cancers unsuitable for intracavitary BT alone to improve target coverage or reduce critical organ dose. There is limited outcome data with the use of these applicators outside published experience of the EMBRACE group. We report feasibility and early outcomes with the use of these hybrid applicators at our institution. METHODS AND MATERIALS: Hybrid applicators were used to treat 61 patients with cervical cancer from November 2011 to December 2019. Indications for hybrid applicator use were involvement of the vagina in 10 patients (16%), residual central or parametrial disease in 46 patients (75%), and a narrow introitus in 5 patients (9%). Toxicities were graded using the CTCAE v4.0. Outcomes were assessed with the Kaplan-Meier method. RESULTS: Median follow-up was 16 months (IQR 9-32 mos). Median HRCTV volume was 31.6 cm3 (IQR 25-48 cm3). Median HRCTV D90 was 86.1 Gy (IQR 84.3-88.0 Gy). In 54 patients with follow-up PET/CT at 3 months, complete initial imaging response locally was seen in 46 patients.Estimated 12-month Kaplan-Meier overall survival, locoregional control, distant control, and recurrence-free survival estimates were 86.9%, 80.6%, 73.8%, and 65.9%, respectively. The 12-month incidence of Grade 3+ GI/GU chronic toxicities was 5.7%, consisting of vesicovaginal fistula, rectovaginal fistula, and ureterovesical fistula. CONCLUSIONS: Our single-institution data support the use of the hybrid applicators, as an alternative to traditional BT applicators when clinically warranted. Use of hybrid applicators is feasible with adequate coverage of disease in the vagina and parametrium.

Is the risk of substantial LVSI in stage I endometrial cancer similar to PORTEC in the North American population? - A single-institution study.

OBJECTIVES: A pooled analysis of PORTEC-1 & 2 identified substantial lymphovascular space invasion (LVSI) in 4.8% of patients, which predicted for pelvic recurrence, distant metastasis, and overall survival. Our institution implemented the PORTEC three-tier system of LVSI reporting (absent, focal, or substantial). We aimed to quantify the incidence of substantial LVSI in a North American population and to correlate extent of LVSI with lymph node (LN) involvement. METHODS: A retrospective review was conducted on patients with clinically uterine-confined, endometrioid type endometrial cancer who underwent surgical staging and were found to have pT1a-b disease. Binary logistic regression was used to assess predictors of LN involvement (defined as ITC, micrometastases, or macrometastases). RESULTS: In total, 438 patients with pT1a-b disease were identified. In the overall cohort and in the subset meeting PORTEC-1 inclusion criteria (n = 195), no LVSI was present in 67.4% and 50.8%; focal LVSI was present in 16.7% and 24.1%; and substantial LVSI was present in 16.0% and 25.1%, respectively. Among patients who underwent surgical LN assessment (79.2%, n = 347), LNs were involved in 3.3% without LVSI, 7.5% with focal LVSI (OR 2.4), and 15.2% with substantial LVSI (OR 5.3) (p = .005), with a similar trend in the PORTEC-1 cohort. Extent of LVSI correlated with disease burden in LN metastases. CONCLUSION: Our incidence of substantial LVSI was three to five times higher than reported by PORTEC and correlated with LN involvement. This questions the reproducibility of the three-tier LVSI reporting system and emphasizes the need for multi-institutional data outside PORTEC for confirmation of our findings.

Human papillomavirus infection mediates response and outcome of vulvar squamous cell carcinomas treated with radiation therapy.

PURPOSE: Human papillomavirus (HPV) is implicated as a causative factor in vulvar squamous cell carcinoma (VSCC). This study evaluates if p16-positivity, a surrogate for HPV, predicts for better response rates to chemoradiation therapy and survival. MATERIALS AND METHODS: We conducted a retrospective chart review of women treated with neoadjuvant or definitive chemoradiation (CRT) therapy from 2000 to 2016 for VSCC. p16 stain-positivity was defined as diffuse strong "block" immunoreactivity within invasive tumor. RESULTS: Seventy-three women with median follow-up of 13.4 months were analyzed. Thirty-three (45.2%) had p16+ tumors. Median age was 73 years (range: 37-89); with p16+ tumors, the median age was 60 years vs 73 years for women with p16- tumors (p < 0.001). The distribution of tumor size and stage by p16-status were similar. The complete clinical response (cCR) rate for p16+ tumors was 63.6% vs 35.0% for p16- tumors (p = 0.014). The pathologic complete response (pCR) rate for women treated neoadjuvantly was 53.8% vs 31.4% for p16+ vs p16-, respectively (p = 0.067). The combined complete response (cCR orpCR [CCR]) rate was 63.6% for p16+ and 30.0% for p16- (p = 0.004). Two-year vulvar control (VC) for women with p16+ tumors was 75.5% vs. 49.5% for p16- (p = 0.008). In women with p16+ tumors who achieved CCR, 2-year VC was 92.3% vs 52.1% for CIR (p = 0.009). For p16- tumors, 2-year VC was 67.3% vs 41.1% for CCR and CIR (p = 0.072). No woman with a p16+ tumor developed distant metastases vs. 7 with p16- tumor (p = 0.013). OS was not statistically different between p16+ cohorts, but was improved for p16- patients with CR vs CIR, 72.9% vs 18.8% (p = 0.026). CONCLUSIONS: p16-positive tumors appear to have better clinical and pathologic response rates and clinical outcomes.

Cost-effectiveness Analysis of Stereotactic Radiosurgery Alone Versus Stereotactic Radiosurgery with Upfront Whole Brain Radiation Therapy for Brain Metastases.

AIMS: Stereotactic radiosurgery (SRS) alone or upfront whole brain radiation therapy (WBRT) plus SRS are the most commonly used treatment options for one to three brain oligometastases. The most recent randomised clinical trial result comparing SRS alone with upfront WBRT plus SRS (NCCTG N0574) has favoured SRS alone for neurocognitive function, whereas treatment options remain controversial in terms of cognitive decline and local control. The aim of this study was to conduct a cost-effectiveness analysis of these two competing treatments. MATERIALS AND METHODS: A Markov model was constructed for patients treated with SRS alone or SRS plus upfront WBRT based on largely randomised clinical trials. Costs were based on 2016 Medicare reimbursement. Strategies were compared using the incremental cost-effectiveness ratio (ICER) and effectiveness was measured in quality-adjusted life years (QALYs). One-way and probabilistic sensitivity analyses were carried out. Strategies were evaluated from the healthcare payer's perspective with a willingness-to-pay threshold of $100 000 per QALY gained. RESULTS: In the base case analysis, the median survival was 9 months for both arms. SRS alone resulted in an ICER of $9917 per QALY gained. In one-way sensitivity analyses, results were most sensitive to variation in cognitive decline rates for both groups and median survival rates, but the SRS alone remained cost-effective for most parameter ranges. CONCLUSIONS: Based on the current available evidence, SRS alone was found to be cost-effective for patients with one to three brain metastases compared with upfront WBRT plus SRS.

Brachytherapy boost for prostate cancer: Trends in care and survival outcomes.

PURPOSE: Androgen suppression combined with elective nodal and dose-escalated radiation therapy recently demonstrated an improved biochemical failure-free survival in men who received external beam radiation therapy (EBRT) plus a brachytherapy boost (BB) compared with dose-escalated external beam radiotherapy (DE-EBRT). We sought to analyze the factors predictive for use of EBRT + BB as compared with DE-EBRT and report resulting survival outcomes on a national level using a hospital-based registry. METHODS AND MATERIALS: We identified 113,719 men from the National Cancer Database from 2004 to 2013 with intermediate- or high-risk prostate cancer who were treated with EBRT + BB or DE-EBRT. We performed univariate and multivariate analyses of all available factors potentially predictive of receipt of treatment selection. Survival was evaluated in a multivariable model with propensity adjustment. RESULTS: For intermediate-risk patients, utilization of BB decreased from 33.1% (n = 1742) in 2004 to 12.5% (n = 766) in 2013 and for high-risk patients, utilization dropped from 27.6% (n = 879) to 10.8% (n = 479). Numerous factors predictive for use of BB were identified. Cox proportional hazards analysis was performed-adjusting for age, Charlson-Deyo comorbidity score, T stage, prostate-specific antigen, Gleason score, and sociodemographic factors-and demonstrated BB use was associated with a hazard ratio of 0.71 (95% confidence interval, 0.67-0.75; p < 0.0005) and 0.73 (95% confidence interval, 0.68-0.78; p < 0.0005) for intermediate- and high-risk patients, respectively. CONCLUSIONS: There has been a concerning decline in the utilization of BB for intermediate- and high-risk prostate cancer patients despite an association with improved on overall survival. Numerous factors predictive for use of BB have been identified.

Oncologic outcomes and patient-reported quality of life in patients with oropharyngeal squamous cell carcinoma treated with definitive transoral robotic surgery versus definitive chemoradiation.

OBJECTIVE: It has been postulated that treatment outcomes are similar between transoral robotic surgery (TORS) and definitive chemoradiation (CRT) for oropharyngeal squamous cell carcinomas (OPSCC). We compared oncologic and quality of life (QOL) outcomes between definitive CRT and definitive TORS. MATERIALS AND METHODS: An observational comparison study was performed on 92 patients treated with TORS±adjuvant therapy and 46 patients treated with definitive CRT between July 2005 and January 2016. The Kaplan Meier method was used for survival analyses, and the Mann-Whitney test was used to compare QOL scores between groups. RESULTS: All patients had T0-T2 and N0-N2 disease, although CRT patients had higher clinical staging (p<0.001). HPV+ disease was present in 79% (n=73) of TORS patients and 91% (n=19) of tested CRT patients. Median follow-up was 22.1months (range: 0.33-83.4). There were no significant differences in locoregional control or overall survival between CRT and TORS groups. Definitive TORS resulted in better saliva-related QOL than definitive CRT at 1, 6, 12, and 24months (p<0.001, p=0.025, p=0.017, p=0.011). Among TORS patients, adjuvant therapy was associated with worse QOL in the saliva domain at 6, 12, and 24months (p<0.001, p<0.001, p=0.007), and taste domain at 6 and 12months (p=0.067, p=0.008). CONCLUSION: Definitive CRT and definitive TORS offer similar rates of locoregional control, overall survival, and disease-free survival in patients with early stage OPSCC. TORS resulted in significantly better short and long-term saliva-related QOL, whereas adjuvant therapy was associated with worse saliva and taste-related QOL compared to TORS alone.

Stage II Testicular Seminoma: Patterns of Care and Survival by Treatment Strategy.

AIMS: Stage II testicular seminoma is highly curable with radiotherapy or multi-agent chemotherapy (MACT). These modalities have not been compared in a randomised manner. MATERIALS AND METHODS: Using the US National Cancer Data Base, we identified 2437 stage II seminoma patients (IIA = 960, IIB = 812, IIC = 665) treated with orchiectomy and either radiotherapy or MACT from 1998 to 2012. Factors affecting treatment modality (radiotherapy versus MACT) were studied using multivariable logistic regression. Propensity scores for treatment selection were incorporated into multivariable Cox regression analyses of overall survival. RESULTS: The median follow-up was 65 months (interquartile range 34-106). Rates of radiotherapy utilisation were: IIA = 78.1%, IIB = 54.4%, IIC = 4.2%. Rates of MACT utilisation were: IIA = 21.9%, IIB = 45.6%, IIC = 95.8%. For both IIA and IIB patients, later year of diagnosis, academic treatment facility and pathological confirmation of lymph node positivity were associated with increased utilisation of MACT. Also predictive for preferential utilisation of MACT were comorbidity score ≥ 1 and non-private insurance for IIA patients and T stage ≥ 2 for IIB patients. For IIA patients, survival was improved with radiotherapy compared with MACT with a 5 year survival of 99.0% (95% confidence interval 98.2-99.8) versus 93.0% (95% confidence interval 89.0-97.0). This advantage persisted on propensity-adjusted multivariate analysis (hazard ratio 0.28; 95% confidence interval 0.09-0.86; P = 0.027). For IIB patients, 5 year survival was 95.2% (95% confidence interval 92.8-97.6) for radiotherapy and 92.4% (95% confidence interval 89.2-95.6) for MACT (Log-rank P = 0.041), with no significant difference on multivariable analysis. CONCLUSIONS: Radiotherapy is associated with improved survival over MACT for IIA patients, with no significant survival difference for IIB patients.

Survival advantage associated with multimodal therapy in women with node-positive (stage-IIIC) uterine papillary serous carcinoma: a National Cancer Database study.

OBJECTIVE: Uterine papillary serous carcinoma (UPSC) is an aggressive subtype of endometrial cancer. Adjuvant chemotherapy (CT) has become standard care in treatment of women with advanced-stage UPSC, but the role of consolidative radiotherapy (RT) is unclear. This study aims to evaluate survival outcomes of multimodal therapy. DESIGN: Retrospective cohort study using a National Cancer Database (NCDB). SETTING: United States of America. SAMPLE: A total of 1816 women diagnosed with UPSC. METHODS: All women diagnosed with surgically staged FIGO (International Federation of Gynecology and Obstetrics) stage-IIIC UPSC were identified in the NCDB from January 1998 to December 2010. Overall survival (OS) was estimated using the Kaplan-Meier method. Univariate and multivariable analyses were performed to identify and control for prognostic factors. MAIN OUTCOME MEASURE: Overall survival. RESULTS: A total of 398 057 cases of uterine cancer were identified, 22 106 of which were UPSC. Of these women, 14 093 underwent lymph-node examination, 2902 (20.6%) were found to have stage-IIIC disease, and 1816 received chemotherapy. Younger age and higher number of total lymph nodes examined were independently predictive of receiving multimodality (CT + RT) therapy, compared with CT only. Median OS was 33.6 and 42.6 months, for the CT and CT + RT groups, respectively (P < 0.0005). Exploratory univariate analyses found age, comorbidity index, tumour size, and number of dissected and positive lymph nodes to be also associated with survival. Multivariable analysis controlling for the above found the use of consolidative radiotherapy to be independently predictive of improved OS, with a hazard ratio of 0.69 (95% confidence interval, 95% CI 0.56-0.84). CONCLUSIONS: Patients with stage-IIIC UPSC may benefit from multimodal treatment that includes adjuvant radiotherapy in addition to chemotherapy. TWEETABLE ABSTRACT: In this study of 1816 women with uterine papillary serous cancer, adjuvant radiotherapy increased survival.

Five year prostate-specific antigen outcomes after caesium prostate brachytherapy.

AIMS: To report 5 year prostate-specific antigen outcomes in men undergoing prostate brachytherapy with caesium 131 at a single institution. MATERIALS AND METHODS: All patients who underwent prostate brachytherapy with caesium 131 at our institution and had at least 24 months of follow-up were included in this study. The results are reported by risk group (low, intermediate and high) as well as by treatment received (monotherapy, combination therapy or trimodal therapy). The Phoenix definition (absolute nadir plus 2 ng/ml) was used to define biochemical freedom from disease (BFD). RESULTS: Four hundred and eighty-five patients underwent prostate brachytherapy with caesium 131 at our institution and 367 patients had at least 24 months of follow-up and were included in this analysis. Using the Phoenix criteria, 5 year actuarial BFD was 96.0% for patients in the low-risk category, 92.7% for patients in the intermediate-risk category and 82.9% for patients in the high-risk category. By treatment category, 95.7% of men treated with monotherapy had BFD, 84.9% of men treated with combination therapy had BFD and 92.0% of men treated with trimodal therapy had BFD. CONCLUSIONS: The present study showed that prostate brachytherapy with caesium 131 achieves excellent oncological outcomes at 5 years.

The impact of ionizing radiation on placental trophoblasts.

INTRODUCTION: Exposure to low-dose radiation is widespread and attributable to natural sources. However, occupational, medical, accidental, and terrorist-related exposures remain a significant threat. Information on radiation injury to the feto-placental unit is scant and largely observational. We hypothesized that radiation causes trophoblast injury, and alters the expression of injury-related transcripts in vitro or in vivo, thus affecting fetal growth. METHODS: Primary human trophoblasts (PHTs), BeWo or NCCIT cells were irradiated in vitro, and cell number and viability were determined. Pregnant C57Bl/6HNsd mice were externally irradiated on E13.5, and placentas examined on E17.5. RNA expression was analyzed using microarrays and RT-qPCR. The experiments were repeated in the presence of the gramicidin S (GS)-derived nitroxide JP4-039, used to mitigate radiation-induced cell injury. RESULTS: We found that survival of in vitro-irradiated PHT cell was better than that of irradiated BeWo trophoblast cell line or the radiosensitive NCCIT mixed germ cell tumor line. Radiation altered the expression of several trophoblast genes, with a most dramatic effect on CDKN1A (p21, CIP1). Mice exposed to radiation at E13.5 exhibited a 25% reduction in mean weight by E17.5, and a 9% reduction in placental weight, which was associated with relatively small changes in placental gene expression. JP4-039 had a minimal effect on feto-placental growth or on gene expression in irradiated PHT cells or mouse placenta. DISCUSSION AND CONCLUSION: While radiation affects placental trophoblasts, the established placenta is fairly resistant to radiation, and changes in this tissue may not fully account for fetal growth restriction induced by ionizing radiation.

Evaluation of set-up uncertainties with daily kilovoltage image guidance in external beam radiation therapy for gynaecological cancers.

AIMS: To assess the set-up uncertainty for gynaecological cancer patients treated with external beam radiation therapy using daily kilovoltage image guidance and to estimate set-up margins for treatment and factors that would predict higher set-up uncertainty. MATERIALS AND METHODS: Alignment data from daily two-dimensional kilovoltage planar images and three-dimensional kilovoltage cone beam images for 52 patients treated on a Varian 2300iX linear accelerator with On Board Imaging (OBI; version 1.4) capability were analysed. The mean displacements of translational shifts, population systematic errors and random errors were calculated. Using van Herk's formula, the clinical target volume (CTV) to planning target volume (PTV) margins for set-up uncertainties were calculated. The differences in set-up error were calculated with respect to the type of cancer, imaging type and body mass index (BMI). RESULTS: Population systematic and random errors were 1.1 mm, 2.3 mm, 2.3 mm and 3.9 mm, 5.0 mm, 3.5 mm in the anterior-posterior (AP), medial-lateral (ML) and superior-inferior (SI) directions, respectively, for the entire patient population. Using van Herk's formula, the CTV to PTV margins for set-up uncertainties were found to be 5.5, 9.1 and 8.3 mm in the AP, ML and SI directions respectively. The mean displacements in the AP, ML and SI directions for BMI ≥ 30 (28 patients) versus <30 (24 patients) were -0.1 mm, 0.9 mm and 1.0 mm versus -0.1 mm, 0.1 mm and 0.4 mm, respectively, (P = 0.02). CONCLUSIONS: Daily imaging helps to assess set-up uncertainty. The set-up margin for CTV to PTV was larger for patients with BMI ≥ 30 without image guidance and these patients would benefit more from daily image guidance.

Concurrent chemotherapy and intensity-modulated radiation therapy for anal carcinoma--clinical outcomes in a large National Cancer Institute-designated integrated cancer centre network.

AIMS: To report the clinical outcomes of patients with anal carcinoma treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy in a large integrated academic-community cancer centre network. MATERIALS AND METHODS: Seventy-eight patients were treated with IMRT for anal carcinoma at 13 community cancer centres. IMRT planning for all centres was carried out at one central location. Sixty-five patients (83%) were T1-T2, 64% were N0, 9% were M1; five patients were HIV positive. All but one patient received concurrent chemotherapy. The median dose to the pelvis including inguinal nodes was 45 Gy. The primary site and involved nodes were boosted to a median dose of 55.8 Gy. All acute and late toxicities were scored according to the Common Terminology Criteria for Adverse Events, version 3.0. RESULTS: The median follow-up for the entire cohort was 16 months (range 0-72 months). Acute grade ≥3 toxicity included 27.7% gastrointestinal and 29.0% dermatological. Acute grade 4 haematological toxicity occurred in 12.9% of patients. Sixty-four (88.9%) patients experienced a complete response. The 2 year colostomy-free survival, overall survival, freedom from local failure and freedom from distant failure rates were 81.2, 86.9, 83.6 and 81.8%, respectively. CONCLUSIONS: Early results seem to confirm that IMRT used concurrently with chemotherapy for treatment of anal carcinoma is effective and well tolerated. This complex treatment can be safely and effectively carried out in a large integrated healthcare network.

Three-dimensional high dose rate intracavitary image-guided brachytherapy for the treatment of cervical cancer using a hybrid magnetic resonance imaging/computed tomography approach: feasibility and early results.

AIMS: To evaluate the feasibility and outcome of image-guided brachytherapy (IGBT) for treating cervical cancer using magnetic resonance imaging (MRI)-based planning for the first fraction followed by computed tomography (CT)-based planning for subsequent fractions. MATERIALS AND METHODS: Forty-four patients with cervical cancer were treated with three-dimensional high dose rate IGBT. The brachytherapy dose was 5.0-6.0 Gy × five fractions. All but five patients received concurrent weekly cisplatinum at 40 mg/m(2). All patients received external beam radiotherapy (EBRT) with a median dose of 45Gy over 25 fractions. Total doses for the high-risk clinical target volume (HRCTV) and organs at risk, including the rectum, bladder and sigmoid, from EBRT and brachytherapy were summated and normalised to a biologically equivalent dose of 2Gy per fraction (EQD(2)). At 3 months after therapy, any early response was assessed with positron emission tomography (PET)/CT imaging. RESULTS: The mean D(90) for the HRCTV was 83.3 (3.0) Gy. The mean 2 cm (3) dose to the bladder, rectum and sigmoid colon organs was 79.7 (5.1), 57.5 (4.4) and 66.8 (5.7) Gy, respectively. All but one (2.3%) patient had a complete response. Follow-up PET/CT was carried out in 41 (93.0%) patients, of whom 38 (92.5%) had a complete response. Of the 38 patients with a complete response on PET/CT, two had local recurrences at 6 and 8 months, respectively. Actuarial 2 year local control, disease-specific and overall survival rates were 88, 85 and 86%, respectively. CONCLUSION: This is the first report of three-dimensional high dose rate IGBT for the treatment of cervical cancer using a hybrid MRI/CT approach. Early results have shown the feasibility of this approach with excellent local control. Additional studies are needed to assess long-term outcomes of local control and associated morbidities.

PET/CT-guided radiation therapy planning: from present to the future.

Molecular imaging using 18F-fluoro-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has been successfully used in the diagnosis, initial staging, and response assessment of various malignant tumors. Advances in radiation therapy planning and delivery have ushered in the era of high-precision conformal radiotherapy allowing generation of dose distributions that conform closely to the shape of the target volume while minimizing high-dose regions in the surrounding normal tissues. Traditionally, radiation therapy planning has relied heavily on CT imaging, but recent times have witnessed tremendous enthusiasm for the use of PET/CT-guidance in radiotherapy planning. This has been largely stimulated by widespread availability and integration with treatment planning systems. However, several issues need to be addressed and challenges overcome to realize the full potential of this exciting technology. Integrating PET/CT fusion imaging into routine clinical practice can be challenging due to technical, administrative, financial, geographic, and personnel issues. Concerted efforts are urgently needed for the development of guidelines for appropriate application of this technology using standardized methodology. There is accumulating evidence that incorporating PET/CT imaging in radiotherapy planning for lung cancer, head and neck cancer and cervical cancer has a significant impact. This review highlights the promises and pitfalls of PET/CT imaging in radiotherapy treatment planning with a critical appraisal of the current best evidence for its application in the modern radiotherapy clinic, and provides a sneak preview into the future of such technology.