Health Services Research in Brachytherapy: Current Understanding and Future Challenges.

Brachytherapy is an integral component of cancer care. Widespread concerns have been expressed though about the need for greater brachytherapy availability across many jurisdictions. Yet, health services research in brachytherapy has lagged behind that in external beam radiotherapy. Optimal brachytherapy utilisation, to help inform expected demand, have not been defined beyond the New South Wales region in Australia, with few studies having reported observed brachytherapy utilisation. There is also a relative lack of robust cost and cost-effectiveness studies, making investment decisions in brachytherapy even more uncertain and challenging to justify, despite its key role in cancer control. As the range of indications for brachytherapy expands, providing organ/function preservation for a wider range of diagnoses, there is an urgent need to redress this balance. By outlining the work undertaken in this area to date, we highlight its importance and explore where further study is required.

Contact X-ray brachytherapy for rectal cancer: Past, present, and future.

The Papillon experience and the Lyon R96-02 trial have shown that contact X-ray brachytherapy of 50kV is efficient and safe to achieve long term local control and organ preservation for cT1 and early cT2-3 rectal cancers. The OPERA trial, using the Papillon 50™ machine, brings further support to this preservation strategy for selected T2T3ab lesions. Future trials using a contact X-ray boost will try to consolidate and enlarge its place in organ preservation for rectal cancers.

No improvement in survival of older women with cervical cancer-A nationwide study.

AIM: This study aims to report trends in primary treatment and survival in cervical cancer (CC) to identify opportunities to improve clinical practice and disease outcome. METHODS: Patients diagnosed with CC between 1989 and 2018 were identified from the Netherlands Cancer Registry (N = 21,644). Trends in primary treatment and 5-year relative survival were analysed with the Cochran-Armitage trend test and multivariable Poisson regression, respectively. RESULTS: In early CC, surgery remains the preferred treatment for ages 15-74. Overall, it was applied more often in younger than in older patients (92% in 15-44; 64% in 65-74). For 75+, surgery use was stable over time (38%-41%, p=0.368), while administration of radiotherapy decreased (57%-29%, p < 0.001). In locally advanced CC, chemoradiation use increased over time (5%-65%, p < 0.001). It was applied least often for 75+, in which radiotherapy remains most common (54% in 2014-2018). In metastatic CC, chemotherapy use increased over time (11%-28%, p < 0.001), but varied across age groups (6%-40% in 2014-2018). In patients treated with primary chemoradiation, regardless of stage, brachytherapy use increased over time (p ≤ 0.001). Full cohort 5-year survival increased from 68% to 74% (relative excess risk 0.55; 95% confidence interval [0.50-0.62]). Increases were most significant in locally advanced CC (38%-60%; 0.55 [0.47-0.65]). Survival remained stable in 75+ (38%-34%; 0.82 [0.66-1.02]). CONCLUSION: Relative survival for cervical cancer increased over the last three decades. The proportion of older patients receiving preferred treatment lags behind. Consequently, survival did not improve in the oldest patients.

Uterine carcinosarcoma: Contemporary clinical summary, molecular updates, and future research opportunity.

Uterine carcinosarcoma (UCS) is a biphasic aggressive high-grade endometrial cancer in which the sarcoma element has de-differentiated from the carcinoma element. UCS is considered a rare tumor, but its incidence has gradually increased in recent years (annual percent change from 2000 to 2016 1.7%, 95% confidence interval 1.2-2.2) as has the proportion of UCS among endometrial cancer, exceeding 5% in recent years. UCS typically affects the elderly, but in recent decades patients became younger. Notably, a stage-shift has occurred in recent years with increasing nodal metastasis and decreasing distant metastasis. The concept of sarcoma dominance may be new in UCS, and a sarcomatous element >50% of the uterine tumor is associated with decreased survival. Multimodal treatment is the mainstay of UCS. Lymphadenectomy, chemotherapy, and brachytherapy have increased in the past few decades, but survival outcomes remain dismal: the median survival is less than two years, and the 5-year overall survival rate has not changed in decades (31.9% in 1975 to 33.8% in 2012). Carboplatin/paclitaxel adjuvant chemotherapy improves progression-free survival compared with ifosfamide/paclitaxel, particularly in stages III-IV disease (GOG-261 trial). Twenty-six clinical trials previously examined therapeutic effectiveness in recurrent/metastatic UCS. The median response rate and progression-free survival were 37.5% and 5.9 months, respectively, after first-line therapy, but after later therapies, the outcomes were far worse (5.5% and 1.8 months, respectively). One significant discovery was that epithelial-mesenchymal transition (EMT) plays a pivotal role in the pathogenesis of sarcomatous dedifferentiation in UCS and that heterologous sarcoma is associated with a higher EMT signature compared with homologous sarcoma. Furthermore, next-generation sequencing has revealed that UCS tumors are serous-like and that common somatic mutations include those in TP53, PIK3CA, FBXW7, PTEN, and ARID1A. This contemporary review highlights recent clinical and molecular updates in UCS. A possible therapeutic target of EMT in UCS is also discussed.

Methodology of dose calculation for external beam radiation combined with high dose rate brachytherapy in the era of 3-dimensional treatment planning system.

Intracavitary application of brachytherapy (BT) sources followed by external beam radiation is essential for the local treatment of carcinoma of the cervix, postate, and nasopharynx. Dose distribution of external beam radiation plus BT can be challenging for the planning system because of their dose calculation by 2 different treatment planning system (TPS). The aims of this study were to introduce a novel iterative method of dose calculation preformed in the Pinnacle plan and evaluate a combined dose distribution for external beam radiation and BT.Because it is often the goal of the planner to produce plan with uniform dose throughout the target volume and normal tissue, we present an Iridium-192 calculation program using American Association of Physicists in Medicine Task Group 43 formula and export it to other commercialized TPS though the combined dose distribution of external beam radiation and BT can be shown. To illustrate such an improved procedure, we present the treatment plans of 2 patients treated with external beam radiation plus BT.Dose distribution of the single BT source were calculated with the Plato post loading TPS and the program model, and the results of 2 methods were similar. A nasopharyngeal case and a cervical case were shown in Pinnacle with this program. The total dose distribution of BT combined with EBRT was showed in compute tomography images. And the corresponding dose volume histogram figures could be displayed correctly in Pinnacle TPS.We demonstrated a novel iterative method of dose calculation preformed in the Pinnacle plan to produce a combined dose distribution for external beam radiation and BT. We used it to evaluate the dose of target volume and normal tissues in the treatment of external beam radiation plus BT.

[Brachytherapy in France in 2020: State of the art and perspectives from the Groupe curiethérapie de la SFRO]. / Curiethérapie en France en 2020 : synthèse et perspectives du Groupe curiethérapie de la Société française de radiothérapie oncologique.

Because of its principle and its high proof level clinical results, brachytherapy represents a specific irradiation technique for the treatment of primary tumors as well as some local relapses in pre-irradiated area. After a glory period between the 80's and 90's, brachytherapy has progressively lost its attractiveness. In order to provide a practical solution to this deleterious situation, it is important that guardianships, health care payers, patient associations, specialist doctors and radiation oncologists understand the reasons leading to this harmful state as well as the risks concerned. A teaching judged insufficient, non-adapted value and an aging image of brachytherapy represent the three main reasons of this degradation and constitute the three most important challenges conditioning its maintain in the anticancer treatment arsenal. An adapted communication with radiation oncologists themselves but also with the other scientific societies remains crucial as well as with guardianship and patient associations. It is central that brachytherapy could be recognized in order to make it stronger and accessible for all the patients who could need it.

Impact of vaginal brachytherapy on survival in stage I endometrioid endometrial carcinoma.

OBJECTIVE: To evaluate trends in use of radiation therapy and its impact on overall survival in low- and high-grade stage I endometrioid endometrial carcinoma. METHODS: Patients with stage I endometrial cancer who underwent hysterectomy from 2004 to 2013 were identified through the National Cancer Database and classified as: stage IA G1/2, stage IA G3, stage IB G1/2, and stage IB G3. Trends in use of vaginal brachytherapy and external beam radiation therapy were assessed. Overall survival was measured from surgery and estimated using the Kaplan-Meier method. The effect of radiation therapy on overall survival was assessed within each stage/grade group using Cox proportional hazards analysis in propensity-matched treatment groups. RESULTS: A total of 132 393 patients met inclusion criteria, and 81% of patients had stage IA and 19% had stage IB endometrial cancer. Adjuvant therapy was administered in 18% of patients: 52% received vaginal brachytherapy, 30% external beam radiation therapy, and 18% chemotherapy ±radiation therapy. External beam radiation therapy use decreased from 9% in 2004 to 4% in 2012, while vaginal brachytherapy use increased from 8% to 14%. Stage IA G1/2 patients did not benefit from either external beam radiation therapy or vaginal brachytherapy, while administration of vaginal brachytherapy improved overall survival in stage IB G1/2 compared with no treatment (p<0.0001). In stage IB G1/2 and stage IA G3, vaginal brachytherapy was superior to external beam radiation therapy (p=0.0004 and p=0.004, respectively). Stage IB G3 patients had improved overall survival with either vaginal brachytherapy or external beam radiation therapy versus no treatment but no difference in overall survival was seen between vaginal brachytherapy and external beam radiation therapy (p=0.94). CONCLUSIONS: The delivery of adjuvant radiation therapy in patients with stage IA G1/2 endometrial carcinoma is not associated with improvement in overall survival. Patients with stage IB G1/2 and G3 as well as stage IA G3 are shown to benefit from improved overall survival when adjuvant radiation therapy is administered. These findings demonstrate potential opportunities to reduce both overtreatment and undertreatment in stage I endometrial cancer patients.

Abscopal effect and interventional oncology: state of art and future perspectives.

OBJECTIVE: The concept of abscopal effect is currently gaining importance in modern oncology, as the link between localized irradiation and triggering of immuno-mediated systemic antitumor effects is getting clearer. An increasing number of reports documented abscopal effect mainly after external beam irradiation. Interventional radiotherapy (IR) may be used with sealed radioactive sources as brachytherapy (BT) or with unsealed radioactive sources as transarterial radioembolization (TARE). The aim of this paper is to review the existing clinical IR data and discuss the mechanisms of the abscopal effect. MATERIALS AND METHODS: A systematic research of the main bibliographic databases (PubMed, WOS, Scopus, and Google Scholar) from the earliest possible date through August 2019 was performed. The search strategy was based on the terms "abscopal effect", "interventional radiotherapy", "brachytherapy" and "TARE". RESULTS: Thirteen titles were identified. Three papers met inclusion criteria and were included in the review. All of them were case reports. CONCLUSIONS: Even though there are still scarce data in literature regarding the association of locoregional interventional treatments with the abscopal effect, this review demonstrates that the immunomodulatory theories, which have been widely used so far for external beam radiotherapy (EBRT), may be actually considered valid also in the contest of IR.

Declining brachytherapy utilization for cervical cancer patients - Have we reversed the trend?

OBJECTIVE: Studies examining temporal trends in cervical brachytherapy use are conflicting and examined different health insurance populations. This study examined brachytherapy utilization over time by health insurance type and whether reported declines in brachytherapy have reversed. METHODS: The National Cancer Database (NCDB) was queried for patients with FIGO IIB-IVA cervical cancer treated with definitive chemoradiotherapy between 2004 and 2014, identifying 17,442 patients. Brachytherapy utilization over time and by insurance type and other sociodemographic factors were compared using binary logistic regression. A sensitivity analysis was done in a sub-cohort of patients using the boost modality variable in the NCDB. RESULTS: Brachytherapy utilization declined during 2008-10 (52.6%) compared to 2004-2007 (54.4%; odds ratio [OR] 0.93, 95% confidence interval [CI] 0.86-1.01) and declines were disproportionately larger for patients with government insurance (49.4% vs 52.3%, respectively) than privately-insured patients (57.6% vs 58.9%, respectively). However, rates of brachytherapy use subsequently recovered during 2011-14 in all insurance groups (58.0%, OR 1.24, 95% CI 1.16-1.34) and was especially improved for Medicaid (OR 1.44, 95% CI 1.26-1.65) and uninsured patients (OR 1.28, 95% CI 1.03-1.57). Sensitivity analysis using the boost modality variable confirmed these trends. CONCLUSIONS: In patients with FIGO IIB-IVA cervical cancer treated with definitive chemoradiotherapy from 2004 to 2014, brachytherapy utilization declined during the late 2000s and disproportionately affected patients with government insurance, but subsequently recovered in the early 2010s. Since government insurance covers vulnerable patient populations at-risk for future declines in brachytherapy use, proposed alternative payment models should incentivize cervical brachytherapy to solidify gains in brachytherapy utilization.

Brachytherapy Future Directions.

Brachytherapy has advanced dramatically in the last decade due largely to improvements in applicators, imaging, treatment planning, and use of clinical trials. In addition, current research in brachytherapy technology continues to change how we deliver this treatment modality. The future of brachytherapy lies in the ability of new technologies to overcome real or perceived barriers. The focus for this manuscript is on specific tools that have or are near to being introduced in the clinic. First, we explore the impact electromagnetic tracking technologies can have on brachytherapy implants and planning workflow. This is followed by an overview of the use of 3D printing and its ability to help tailor brachytherapy implants. Next, we discuss advances in self-shielded applicators and intensity-modulated brachytherapy technology. The manuscript closes out with 2 sections on treatment planning. First is a discussion of biological optimization and its potential as compared with current techniques (eg, based on physical dosimetry). And lastly, a section on optimization treatment planning efficiencies in which we explore the potential for machine learning in brachytherapy. As recent clinical evidence continues to show excellent outcomes, this is an exciting time to practice brachytherapy. With the new technologies presented here, the future is even brighter.

Contemporary prostate cancer treatment choices in multidisciplinary clinics referenced to national trends.

BACKGROUND: The purpose of this study was to assess treatment choices among men with prostate cancer who presented at The University of Texas MD Anderson Cancer Center multidisciplinary (MultiD) clinic compared with nationwide trends. METHODS: In total, 4451 men with prostate cancer who presented at the MultiD clinic from 2004 to 2016 were analyzed. To assess nationwide trends, the authors analyzed 392,710 men with prostate cancer who were diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. The primary endpoint was treatment choice as a function of pretreatment demographics. RESULTS: Univariate analyses revealed similar treatment trends in the MultiD and SEER cohorts. The use of procedural forms of definitive therapy decreased with age, including brachytherapy and prostatectomy (all P < .05). Later year of diagnosis/clinic visit was associated with decreased use of definitive treatments, whereas higher risk grouping was associated with increased use (all P < .001). Patients with low-risk disease treated at the MultiD clinic were more likely to receive nondefinitive therapy than patients in SEER, whereas the opposite trend was observed for patients with high-risk disease, with a substantial portion of high-risk patients in SEER not receiving definitive therapy. In the MultiD clinic, African American men with intermediate-risk and high-risk disease were more likely to receive definitive therapy than white men, but for SEER the opposite was true. CONCLUSIONS: Presentation at a MultiD clinic facilitates the appropriate disposition of patients with low-risk disease to nondefinitive strategies of patients with high-risk disease to definitive treatment, and it may obviate the influence of race.

Disparities in the Use of Adjuvant External Beam Radiation Therapy in Node-positive Cervical Cancer Patients Following Hysterectomy.

OBJECTIVE: The objective of this study was to investigate the use of adjuvant external beam radiation therapy (EBRT) among patients with early-stage cervical carcinoma metastatic to regional lymph nodes (LNs). MATERIALS AND METHODS: The National Cancer Database was accessed and patients with early-stage cervical carcinoma diagnosed between 2004 and 2015 were identified. Those with regional LN metastases who had a hysterectomy were selected and administration of adjuvant EBRT was evaluated. Travel distance from the reporting facility was categorized into short (<12.5 miles), intermediate (12.5 to 49.9 miles) and long (>49.9 miles). RESULTS: A total of 3436 patients met the inclusion criteria; the rate of EBRT use was 69.7%. Black women were less likely to receive EBRT compared with white (64.2% vs. 70.6%, P=0.037), while patients who had radical hysterectomy were more likely to receive EBRT compared with those who had simple hysterectomy (72.6% vs. 66%, P<0.001). Rates of EBRT administration for patients who traveled short distance was 74.3% compared with 68.9% and 56.9% for those who traveled intermediate and long distance, respectively (P<0.001). On multivariate analysis, patients who traveled long (odds ratio: 0.44, 95% confidence interval [CI]: 0.36, 0.54) or intermediate (OR: 0.73, 95% CI: 0.61, 0.86) distances were less likely to receive EBRT. After controlling for age, race, insurance, presence of comorbidities, stage, histology, and type of hysterectomy, omission of EBRT was associated with worse survival (hazard ratio: 1.53, 95% CI: 1.32, 1.78). CONCLUSIONS: A large percentage of patients with early-stage cervical cancer and positive LNs did not receive EBRT following hysterectomy. Black women were less likely to receive EBRT than white women. Travel burden may negatively influence appropriate treatment.

Quality of life outcomes after low dose-rate brachytherapy for localized prostate cancer: Current status and future perspectives.

The present review summarizes data from studies reporting on health-related quality of life after brachytherapy and competing modalities. There are various therapeutic modalities for localized prostate cancer, including radical surgery, external beam radiotherapy and active surveillance. Advances in surgical and radiation treatment have entered clinical practice in the form of robot-assisted surgery or intensity-modulated radiotherapy. Brachytherapy remains the main treatment option for patients with localized prostate cancer, with 10-year survival data showing favorable outcomes. Because each treatment modality has achieved favorable survival outcomes, focus in determining appropriate treatment has shifted toward health-related quality of life, where each treatment has a different profile and/or adverse symptoms. The development of health-related quality of life assessment tools has allowed the creation of a pool of specific health-related quality of life data across many studies. The present article reviews the impact of brachytherapy and other modalities on quality of life, as well as future directions.

[Brachytherapy: When needs overtake care offer]. / Curiethérapie : quand les indications dépassent l'offre de soins.

Brachytherapy has the unique characteristic of being able to deliver high doses to a very localized volume, and remains one of the radiotherapy techniques that has an unparalleled therapeutic index. However, its use has been declining in the past years. Globally, only 55 to 88 % of patients with locally advanced cervical cancer benefit from utero-vaginal brachytherapy, despite the fact that it is proven to enhance both progression-free and overall survival. A decline in the use of low dose rate brachytherapy has likewise been described in the treatment of low-risk and favorable intermediate-risk prostate cancers. Several factors could explain this. First, the radiation oncologists who have the proficiency to perform brachytherapy seems to be inadequate, as it is a technique that requires training and expertise for optimal applications. In many cancer care centers, the caseload is insufficient to provide this experience. Second, the increasing use of technically advanced external beam radiation therapy, such as intensity modulated radiation therapy, offers an easier substitute with more lucrative benefits, resulting in decreased utilization of brachytherapy. However, when brachytherapy is not delivered, a poorer survival rate is reported in locally advanced cervical cancer, and is suggested in intermediate and high-risk prostate cancer. The increasing level of evidence of treatment with brachytherapy necessitates an improvement in its accessibility by having more radiation oncologists as well as cancer centers equipped to perform the procedure.

Brachytherapy: A critical component of primary radiation therapy for cervical cancer: From the Society of Gynecologic Oncology (SGO) and the American Brachytherapy Society (ABS).

Brachytherapy is well-established as an integral component in the standard of care for treatment of patients receiving primary radiotherapy for cervical cancer. A decline in brachytherapy has been associated with negative impacts on survival in the era of modern EBRT techniques. Conformal external beam therapies such intensity modulated radiation therapy (IMRT) or stereotactic body radiation therapy (SBRT) should not be used as alternatives to brachytherapy in patients undergoing primary curative-intent radiation therapy for cervical cancer. Computed tomography or magnetic resonance image-guided adaptive brachytherapy is evolving as the preferred brachytherapy method. With careful care coordination EBRT and brachytherapy can be successfully delivered at different treatment centers without compromising treatment time and outcome in areas where access to brachytherapy maybe limited.