The role of brachytherapy in treatment of stage I esophageal cancer: A systematic review

PURPOSEDespite advancements in the early detection of esophageal cancer, optimal radiotherapy methods for treatment of early disease have not yet been determined. Moreover, the benefit of intraluminal brachytherapy on local control or survival remains controversial. We performed a systematic review to establish the role of brachytherapy as boost therapy in stage I esophageal squamous cell carcinoma, and to evaluate associated survival outcomes.METHODS AND MATERIALSA systematic search of three bibliographic databases from January 1950 to January 2019 was conducted. All studies investigating brachytherapy for curative intent were included and palliative treatment was excluded. Primary outcomes included overall survival and disease-free survival (DFS). Secondary outcomes included loco-regional control (LRC) and toxicity grades and/or complications. Two reviewers independently abstracted data and evaluated study quality using grading of recommendations assessment, development, and evaluation, pooled results were presented through risk ratios.RESULTSA total of 12 retrospective studies met inclusion criteria. The overall quality of evidence yielded a Grade 1C rating (strong recommendation, low quality evidence). Of 525 included patients, 325 patients received both external beam radiation (EBRT), and brachytherapy, 132 underwent EBRT only, and 68 received brachytherapy with and/or without chemoradiation. For patient group treated with EBRT and brachytherapy, 5-year mortality, DFS and LRC were: 43% (27–59%), 63% (49–76%) and 72% (63–80%) respectively. Rates of complications reported included 82.1% Grade 1 esophagitis for a combined external beam radiation and brachytherapy cohort, 12.3% ulcerations, and 3.3% fistulae.CONCLUSIONSBrachytherapy as a combined modality is encouraging, given its relative safety and effectiveness. Further prospective analysis using higher quality evidence is warranted to evaluate oncologic outcomes and survival advantage.     

The American Brachytherapy Society consensus statement for electronic brachytherapy

PurposeBrachytherapy is utilized in the treatment of many different malignancies; although traditionally performed with low-dose-rate or high-dose-rate techniques, more recently, electronic brachytherapy (EB) has emerged as a potential alternative. At this time, there are no evidence-based guidelines to assist clinicians in patient selection for EB and concerns exits regarding differences in dosimetry as compared to traditional brachytherapy techniques. As such, the American Brachytherapy Society appointed a group of physicians and physicists to create a consensus statement regarding the use of EB.Methods and MaterialsPhysicians and physicists with expertise in brachytherapy created a site-directed consensus statement for appropriate patient selection and utilization of EB based on a literature search and clinical experience.ResultsEB has been utilized to deliver accelerated partial breast irradiation with, thus far acceptable local control and toxicity rates including a randomized trial that used EB to deliver intraoperative radiotherapy; however, prospective data with large patient numbers and long-term follow up are needed. Increasing numbers of patients have been treated with EB for nonmelanomatous skin cancers; although, preliminary data are promising, there is a lack of data comparing EB to traditional radiotherapy techniques as well as a lack of long-term follow up. For treatment of the vaginal cuff with EB, small retrospective studies have been reported without long-term follow up.ConclusionsIn light of a randomized trial in breast showing higher rates of recurrence and the lack of prospective data with mature follow up with other sites, as well as concerns regarding dosimetry, it is not recommended that EB be utilized for accelerated partial breast irradiation, nonmelanomatous skin cancers, or vaginal cuff brachytherapy outside prospective clinical trials at this time.     

Clinical outcomes and dosimetric predictors of toxicity for re-irradiation of vaginal recurrence of endometrial cancer

OBJECTIVETo report clinical outcomes and dosimetric predictors of late toxicity for patients with vaginal recurrence of endometrial cancer treated with brachytherapy in the re-irradiation setting.METHODSOn retrospective review, 32 patients with vaginal recurrence of endometrial cancer received salvage brachytherapy with or without pelvic radiotherapy (RT) from 06/2003–12/2017. Prior RT modalities were vaginal brachytherapy (19, 59%), pelvic RT (7, 22%) or both (6, 19%). Image-guided brachytherapy was performed with CT- (25, 78%) or MR-guidance (7, 22%). Vaginal control, recurrence-free survival (RFS) and overall survival (OS) were estimated by Kaplan-Meier method. Late toxicity was graded by Common Toxicity Criteria for Adverse Events.RESULTSMedian time from prior RT to re-irradiation was 22 months (range, 4–140). Salvage RT modalities were pelvic RT and brachytherapy (25, 78%) or brachytherapy alone (7, 22%). With median follow-up of 47 months, 3/5-year vaginal control, RFS and OS rates were 64/56%, 47/41% and 68/42%, respectively. Six patients (19%) had no evidence of disease at 85–155 months. Late grade 2/3 GI, GU and vaginal toxicity rates were 13%/16%, 19%/13%, and 9%/16%. Cumulative D2cc rectum (sum of prior and salvage RT courses) was predictive of grade 2+ and grade 3 GI toxicity. Cumulative D2cc rectum for an estimated 10% risk of late grade 2+ and 3 GI toxicity was 86 Gy and 92 Gy, respectively.CONCLUSIONSSalvage image-guided brachytherapy in the re-irradiation setting results in modest local control and increased late toxicity for localized recurrent endometrial cancer. With long-term disease control, cumulative D2cc rectum may be used to reduce late GI complication risk.     

Vaginal brachytherapy alone for patients with Stage II endometrial cancer with inner half cervical stromal invasion

PurposeThe purpose of this study was to review outcomes of women with Stage II endometrial carcinoma with inner half cervical stromal invasion treated with adjuvant vaginal brachytherapy (VB) alone.Methods and MaterialsA single-institution retrospective chart review identified consecutive patients with Stage II endometrial cancer and inner half cervical stromal invasion treated with VB alone from 2011 to 2015. Patients who received chemotherapy or external beam radiotherapy were excluded. Patient and disease characteristics were collected. Association between variables and outcomes were assessed using Fisher's exact or Wilcoxon rank sum test.ResultsFifty-seven patients were identified over 5 years with a median followup of 46.8 months. Carcinoma was endometrioid Grade 1 (43.9%), 2 (36.8%), 3 (5.3%), or serous (14.0%). Depth of myometrial invasion was inner half in 75.4%. Lymphovascular invasion was seen in 28.1%, and lymph node assessment was performed in 43.9% of patients. The median depth of cervical stromal invasion was 1.25 mm (n = 48 patients). The median percentage of the cervical stromal wall invaded by tumor (obtained in 40 patients) was 16.7%. Seven (12.3%) patients recurred at a median of 16.9 months. Five-year estimates of progression-free survival and overall survival were 81.5% and 78.5%, respectively. The only factor associated with recurrence, progression-free survival or overall survival on bivariate analysis was high-grade (Grade 3 or serous) disease (p = 0.031).ConclusionsVB alone can be considered for Stage II patients with inner half cervical stromal invasion and Grade 1–2 disease. Systemic therapy may be required for patients with Grade 3 and serous histology as 75% (3/4) of these recurrences were outside the pelvis.     

Long term outcomes of Carcinoma Buccal Mucosa treated with High Dose Rate Interstitial Brachytherapy

PURPOSE: To analyze the long-term local control, overall survival and toxicity in Carcinoma Buccal Mucosa patients treated with interstitial brachytherapy.METHODS AND MATERIALS: This analysis included patients diagnosed as Carcinoma Buccal Mucosa on biopsy and treated with radical brachytherapy or External Beam Radiotherapy (EBRT) followed by brachytherapy boost. All patients received High dose rate (HDR) interstitial brachytherapy. The total dose was 35 Gy in ten fractions for brachytherapy alone. Patients who received EBRT (50–54 Gy) were boosted by brachytherapy to a dose of 18–24 Gy in 6–8 fractions. All patients were treated using CT based planning.RESULTS: Between 2007 to 2017, a total of 24 patients of Carcinoma Buccal Mucosa received HDR interstitial brachytherapy either alone or as a boost. Majority of the patients were tobacco chewers (80%). 17(71%) patients were clinical stage T2N0M0 and 7(29%) were clinically T1N0M0. At a median follow up of 7 years (3–12 years), the local control rate was 100% in stage I and 88% in stage II. The 5 year overall survival rate was 80%. Two patients developed nodal recurrence and one patient developed distant metastasis within two years of treatment. Tumor size and brachytherapy technique (radical vs. boost) did not impact local control or overall survival (p > 0.05). Majority of the acute toxicities were Grade 1 and 2. One patient developed osteoradionecrosis of the mandible.CONCLUSIONS: Interstitial brachytherapy in early-stage Buccal Mucosa cancer either alone or as a boost provides excellent long term local control and overall survival. The acute and late toxicities are acceptable with majority of the patients presenting with Grade 1 or 2 toxicity.     

Esophageal brachytherapy: Institut Gustave Roussy's experience

PurposeEsophageal cancer is characterized by its propension to local evolution, which conditions prognosis and quality of life. Brachytherapy may be a therapeutic option for all stages of esophageal cancer.Methods and MaterialsThis retrospective unicentric study included all consecutive patients treated for an esophageal high-dose-rate brachytherapy in our institution from 1992 to 2018.ResultsNinety patients were included. They were treated in four distinct indications: exclusive (7 patients), boost after external beam radiotherapy (41), reirradiation (36), or palliative aim (6). Most frequently prescribed schemes were 3 × 5 Gy (boost) or 6 × 5 Gy (exclusive treatment and reirradiation) at applicator's surface or at 5 mm. At the end of follow-up, 50% of patients had presented with local recurrence. Seventeen percent of patients had a metastatic relapse. Median overall survival was 15 months in the whole cohort: 22 months in the boost setting, 25 months for exclusive brachytherapy, 15 months for reirradiation, and only 2 months for palliative treatment. Tumor length at brachytherapy, brachytherapy dose, and interfraction response were significantly associated to overall survival. 40% of patients presented with grade 2+ toxicity, mostly esophagitis, including three toxic deaths.ConclusionsAlthough local control outcomes are still poor, one must remember that patients are unfit for any curative therapeutic option and that palliative chemotherapy offers mediocre results. The most promising setting probably is reirradiation because brachytherapy offers a remarkable dose gradient allowing best organ at risk sparing, with an encouraging rate of long survivors (19% at 2 years). Esophageal brachytherapy deserves to be further investigated because some patients, even unfit, may benefit from it, with acceptable toxicity.     

The impact of brachytherapy boost and radiotherapy treatment duration on survival in patients with vaginal cancer treated with definitive chemoradiation

PurposeVaginal cancer is a rare tumor that is optimally treated with a combination of chemotherapy (CHT) and radiation therapy. Because of the rarity of this cancer, the benefit of a brachytherapy boost (BT) and the relevance of radiotherapy time to treatment completion (TTC) are unclear.MethodsPatients diagnosed between 2004 and 2015 with non-metastatic vaginal cancer treated with definitive CHT and external beam radiotherapy with or without BT but with no surgery were identified in the National Cancer Database. Overall survival (OS) was assessed with Kaplan-Meier curves, and differences between groups were compared with the log-rank test. A Cox model was constructed to evaluate survival after controlling for confounders. A Cox model using a penalized spline function was constructed to evaluate how the length of radiation therapy correlated with OS among patients receiving BT.ResultsA total of 1094 patients who met the inclusion criteria were identified. The utilization of BT was associated with improved 5-year OS (62.9% vs. 49.3%, p = 0.0126) on propensity score-weighted analyses. TTC of 63 days or less was associated with improved 5-year OS (67.8% vs. 54.5%, p = 0.0031) in patients who underwent BT. Other factors associated with improved OS in patients who received CHT, external beam radiotherapy, and BT were younger age, absent comorbidity score, and negative lymph nodes.ConclusionsA brachytherapy boost and shorter TTC were associated with a survival benefit in a cohort of patients with non-metastatic vaginal cancer treated with definitive chemoradiotherapy.     

Brachytherapy focal dose escalation using ultrasound based tissue characterization by patients with non-metastatic prostate cancer: Five-year results from single-center phase 2 trial

PURPOSEThis prospective trial investigates side effects and efficacy of focal dose escalation with brachytherapy for patients with prostate cancer.METHODS AND MATERIALSIn the Phase II, monocentric prospective trial 101 patients with low-/intermediate- and high-risk prostate cancer were enrolled between 2011 and 2013. Patients received either PDR-/HDR-brachytherapy alone with 86–90 Gy (EQD2, α/β = 3 Gy) or PDR-/HDR-brachytherapy as boost after external beam radiation therapy up to a total dose of 91–96 Gy (EQD2, α/β = 3 Gy). Taking place brachytherapy all patients received the simultaneous integrated focal boost to the intra-prostatic tumor lesions visible in computer-aided ultrasonography (HistoScanning?) - up to a total dose of 108–119 Gy (EQD2, α/β = 3 Gy). The primary endpoint was toxicity. Secondary endpoints were cumulative freedom from local recurrence, PSA-free survival, distant metastases-free survival, and overall survival. This trial is registered with ClinicalTrials.gov, number NCT01409876.ResultsMedian follow-up was 65 months. Late toxicity was generally low with only four patients scoring urinary grade 3 toxicity (4/101, 4%). Occurrence of any grade of late rectal toxicities was very low. We did not register any grade ≥2 of late rectal toxicities. The cumulative 5 years local recurrence rate (LRR) for all patients was 1%. Five years- biochemical disease-free survival estimates according Kaplan-Meier were 98,1% and 81,3% for low-/intermediate-risk and high-risk patients, respectively. Five years metastases-free survival estimates according Kaplan-Meier were 98,0% and 83,3% for all patients, low-/intermediate-risk and high-risk patients, respectively.ConclusionsThe 5 years-results from this Phase II Trial show that focal dose escalation with computer-aided ultrasonography and brachytherapy for patients with non-metastatic prostate cancer is safe and effective.     

Role of brachytherapy in stage III endometrial cancer treated with adjuvant chemotherapy: Identifying factors predictive of a survival benefit

OBJECTIVESTo determine which patients with stage III endometrial cancer receiving adjuvant chemotherapy derive benefit from the addition of vaginal brachytherapy, as stage III is a highly heterogeneous population with substantial variations in practice.METHODSPatients with FIGO stage III endometrial carcinoma diagnosed 2004–2016 who underwent at least total hysterectomy and adjuvant multiagent chemotherapy were identified in the National Cancer Database. The primary outcome was overall survival according to receipt of brachytherapy, stratified by histologic type, pathological features, and status of pelvic external beam radiotherapy (EBRT), and analyzed using the Kaplan-Meier method and Cox multivariable regression.RESULTSIn total, 9369 patients were identified (24% stage IIIA, 5% stage IIIB, 71% stage IIIC; 61% endometrioid, 39% nonendometrioid histology), and 28% received brachytherapy. In the endometrioid cohort, brachytherapy was associated with a 5% absolute increase in 3-year overall survival (87% vs. 82%, p < 0.0001), which persisted in multivariable analysis (adjusted hazard ratio 0.74, 95% confidence interval 0.64–0.84, p < 0.0001). The benefit of brachytherapy was greater in patients not also receiving EBRT, and in patients with vaginal/parametrial extension, grade 3 disease, lymphovascular invasion, and/or deep myometrial invasion. In the nonendometrioid cohort, brachytherapy was associated with a significant survival benefit in univariable but not multivariable analysis, regardless of EBRT status or pathological features.CONCLUSIONSFactors predictive of brachytherapy benefit were endometrioid histology and pathological risk factors for local recurrence. Additionally, brachytherapy appeared more beneficial in patients not already receiving pelvic EBRT. Further research is warranted to determine which stage III patients may be best served by brachytherapy, EBRT, or both.     

High-dose-rate interstitial brachytherapy for vaginal endometrial cancer recurrence after prior surgery and radiotherapy

PurposeCharacterize the clinical outcomes of endometrial cancer vaginal recurrences after previous surgery and radiation therapy treated with reirradiation including image-guided interstitial high-dose-rate (HDR) brachytherapy.Methods and materialsA single-institution retrospective study identifying women receiving reirradiation for vaginal recurrence of endometrial cancer between 2004 and 2017.ResultsTwenty-three women had vaginal recurrences of endometrial cancer, median 13.7 months (range 3.5–104.9) from initial radiation. All received reirradiation with interstitial HDR brachytherapy, and seven also received external beam radiation. Median reirradiation EQD2_10 was 48 Gy (range 24.0–68.81), and median cumulative EQD2_10 was 106.25 Gy (range 62.26–122.0). Median follow-up after reirradiation was 40.2 months (range 4.5–112.7). At 3 years, overall survival was 56%, cancer-specific survival was 61%, and disease-free survival was 46%. 14 patients experienced disease recurrence; 10 including distant sites, one at a regional node only. Three patients experienced local recurrences, two of whom did not complete the prescribed course of reirradiation. The overall crude local control rate was 87%. Three patients experienced Grade 3 vaginal toxicity. There was no bladder or rectal toxicity with Grade >2.ConclusionsReirradiation including interstitial HDR brachytherapy is a promising option for vaginal recurrences of endometrial cancer after prior radiation, with high rate of local control and acceptable toxicity. However, distant failure is common. Further studies are needed to determine cumulative radiation dose limits and the role of systemic therapy in this scenario.     

碳离子治疗前列腺癌的Meta分析

目的 采用Meta分析的方法定量评价碳离子治疗前列腺癌的有效性。方法 检索PubMed、Cochrane library、EMBASE、中国期刊全文数据库、中国生物医学文献数据库、万方数据库,同时追溯纳入研究的参考文献,收集碳离子治疗前列腺癌的临床试验,提取数据,检索时限均为建库至2015年12月。采用MetaAnalyst Beta 3.13和STATA 12.0进行Meta分析。结果 共纳入6个研究（8个临床试验）,Meta分析结果显示,3、4、5和8年的总生存率分别为95.7%、90.9%、91.8%和83.9%,4年和5年肿瘤特异生存率分别为97.1%和97.6%,4、5和8年无生化复发率分别为88%、86.3%和79.1%,3、4和5年的局部控制率分别为98.1%、97.1%和98.4%,总死亡率、前列腺癌死亡率和并发症死亡率分别为7%、2.4%和7%。不同T分期对5年总生存率、无生化复发率和肿瘤特异生存率产生影响。结论 碳离子是一种安全、有效、可行的前列腺癌治疗方法,具有临床应用的前景,但是否优于其他放射治疗,尚需在前列腺癌患者中进行高质量前瞻性、随机对照临床研究。     

Association of Brachytherapy Boost with Overall Survival for Gleason 9-10 Prostate Cancer: The Impact of Primary versus Secondary Pattern 5

PURPOSEThe addition of a brachytherapy (BT) boost to external beam radiotherapy (EBRT) reduces recurrence risk in men with high-risk prostate cancer (PCa) and may reduce PCa-mortality for Gleason grade group 5 (GG5). Whether the extent of pattern five, a risk factor for distant metastases, impacts the benefit of a BT boost is unclear.METHODSMen with localized GG5 PCa treated with (1) EBRT or (2) EBRT+BT between 2010 and 2016 were identified in the National Cancer Database. EBRT monotherapy group received conventionally fractionated (1.8−2.0 Gy per fraction) ≥74 Gy or moderately hypofractionated (2.5−3.0 Gy per fraction) ≥60 Gy. EBRT + BT group received conventionally fractionated ≥45 Gy or moderately hypofractionated ≥37.5 Gy, and either LDR or HDR BT. All patients received concomitant ADT; none received chemotherapy, immunotherapy, or surgery. OS was compared using Kaplan-Meier, log-rank test, and multivariable Cox proportional hazards in the overall cohort, followed by subgroups based on primary versus secondary pattern 5. Propensity score- and exact-matching was used to corroborate results.RESULTSA total of 8260 men were eligible: EBRT alone (89%) versus EBRT + BT (11%). 5-year OS for EBRT versus EBRT + BT was 76.3% and 85.0%, respectively (p = 0.002; multivariable adjusted HR 0.84, 95% CI 0.65−0.98; p = 0.04). These results remained consistent after propensity score and exact matching. The OS advantage of a BT boost was more prominent in men with Gleason 4 + 5 PCa (p = 0.001) and not observed in men with Gleason 5 + 5 or 5 + 4 PCa.CONCLUSIONSExtent of pattern five may be useful in appropriately selecting men for EBRT+BT and should be considered as a pre-randomization stratification variable for future clinical trial design.     

Template-based high-dose-rate interstitial brachytherapy in gynecologic cancers: A single institutional experience

PurposeTo report the outcome and toxicities of radical external beam radiotherapy (EBRT) and template-based high-dose-rate interstitial brachytherapy (ISBT) in patients diagnosed with cervical cancer undergoing inadvertent surgery, vault cancers, and vaginal cancers at our institution.Methods and MaterialsBetween January 2000 and December 2008, 113 patients (37 patients of cervical cancer post-inadvertent surgery, 57 patients with vault cancers, and 19 patients with primary vaginal cancers) were treated with Martinez Universal Perineal Interstitial Template brachytherapy boost after EBRT. The median EBRT dose was 50 Gy, median ISBT dose was 20 Gy, whereas median total dose was 73 Gy equivalent dose at 2 Gy per fraction in all three groups.ResultsMedian followup of surviving patients for the whole group was 43 months (interquartile range, 19–67 months). The 3-year actuarial disease-free survival and overall survival for three groups was 61%, 61%, 59% and 64%, 64%, and 56%, respectively. Grade III/IV rectal toxicity was seen in 11 (10%) patients, bladder toxicity in 5 (4.5%) patients, whereas 7 (6%) patients developed Grade III small bowel toxicity. Residual disease at brachytherapy had significant impact on DFS and OS. Other factors such as age, disease volume, parametrial extension, and vaginal extension did not impact the survivals.ConclusionsMartinez Universal Perineal Interstitial Template–based high-dose-rate ISBT boost in gynecologic cancer results in a reasonable outcome in terms of survivals with acceptable late toxicities. The use of template-based ISBT is associated with a definite learning curve.     

Change in vaginal length and sexual function in women who undergo surgery ± radiation therapy for endometrial cancer

PURPOSEEndometrial Cancer (EC) is the most common gynecologic malignancy in the United States. Standard treatment is TAH/BSO with radiation therapy (RT) and chemotherapy given based on risk. Treatment can cause significant vaginal changes, including shortening, narrowing, loss of elasticity, atrophy, and dryness. These are not life threatening, but affect a woman's physical, psychological, and social functioning. Adjuvant vaginal dilator use is often advised, but there are inconsistent recommendations on use. This prospective study compared vaginal length changes and sexual function in women compliant with dilation versus not after surgery and RT.METHODS AND MATERIALSEnrolled patients underwent surgery for Stage I-IIIC EC ±RT. Vaginal dilator use was recommended for women receiving RT (external beam or brachytherapy). Vaginal length was measured with a vaginal sound and the Female Sexual Function Index (FSFI) was used to assess sexual function.RESULTSForty-one enrolled patients had sufficient data for analysis. Dilation significantly increased FSFI scores (p = 0.02) while RT without dilation showed a significant decrease (p = 0.04). Dilation helped maintain vaginal length for all patients (0 cm vs. 1.8 cm loss (p = 0.03)). Individual arms did not show statistically significant changes in length with dilation, though the trend showed RT without dilation had an average loss of 2.3 cm as compared to only 0.2 cm for regular dilation. Notably, there was no difference in length change with dilation for surgery alone versus surgery and RT (p = 0.14).CONCLUSIONThis data provides novel, prospective evidence of the benefit of vaginal dilation for maintaining vaginal length and improving sexual health after any pelvic treatment for EC. This evidence also supports that the addition of RT after surgery does not appear to significantly worsen vaginal shortening. This study has important implications for providing a strong foundation for future studies and helping to establish solid clinical management criteria for the prevention of vaginal stenosis and promotion of female sexual health.     

The impact of brachytherapy boost for anal canal cancers in the era of de-escalation treatments

PURPOSETo analyze clinical outcomes of high-dose-rate (HDR) interstitial brachytherapy boost (ISBT) after external beam radiation therapy (EBRT) or chemoradiotherapy (CRT) for the treatment of anal canal cancers (ACC).METHODS AND MATERIALSA total of 78 patients with ACC were treated at our institution by ISBT. Local Control (LC), disease-free survival (DFS), overall survival (OS), colostomy-free survival (CFS) and toxicity rates were analyzed.RESULTSWith a median followup (FU) of 59.8 months (95% CI [55.8–64.2]), six (7.7%) local recurrences with 2 patients (2.6%) having persistent disease at 3 months were observed. The 5-year rate of LC for the entire population was 92% [83–96%]. The 5-year DFS rate was 86% [76–93%]. The 5-year OS was 96% [88–99%]. In the univariate analysis, chemotherapy was significantly associated with morbidity grade ≥2. Late digestive toxicity grade ≥3 was reported in 8.9% patients, 1 patient underwent colostomy due to toxicity. The 5-year CFS rate was 88% [79–94%].CONCLUSIONSHDR interstitial brachytherapy boost provide excellent rates of tumor control and colostomy-free survival with a favorable profile of GI toxicity. Continence in anal cancer survivors is a challenge and the boost technique must be discussed in a multidisciplinary approach as part of de-escalation treatments.     

Intra-Arterial Therapy for Unresectable Colorectal Liver Metastases: A Meta-Analysis

PurposeTo evaluate the efficacy of hepatic arterial infusion (HAI), conventional transarterial chemoembolization, drug-eluting embolic transarterial chemoembolization (DEE-TACE), transarterial radioembolization, and their combinations with systemic chemotherapy (SCT) for unresectable colorectal liver metastases.MethodsA search was conducted on Embase, Scopus, PubMed, and Web of Science for prospective nonrandomized studies and randomized controlled trials (RCTs) from inception to June 20, 2020. Survival data of patients were recovered from original Kaplan-Meier curves by exploiting a graphical reconstructive algorithm. One-stage meta-analyses were conducted for the median overall survival (OS), survival rates (SRs), and restricted mean survival time (RMST), whereas two-stage meta-analyses of proportions were conducted to determine response rates (RRs) and conversion to resection rates (CRRs).ResultsA total of 71 prospective nonrandomized studies and 21 RCTs were identified, comprising 6,695 patients. Among patients treated beyond the first-line, DEE-TACE + SCT (n = 152) had the best survival outcomes of median OS of 26.5 (95% confidence interval [CI], 22.5–29.1) months and a 3-year RMST of 23.6 (95% CI, 21.8–25.5) months. Upon further stratification by publication year, DEE-TACE + SCT appeared to consistently have the highest pooled SRs at 1 year (81.9%) and 2 years (66.1%) in recent publications (2015–2020). DEE-TACE + SCT and HAI + SCT had the highest pooled RRs of 56.7% (I² = 0.90) and 62.6% (I² = 0.87) and pooled CRRs of 35.5% (I² = 0.00) and 30.3% (I² = 0.80), respectively.ConclusionsAlbeit significant heterogeneity, the paucity of high-quality evidence, and the noncomparative nature of all analyses, the overall evidence suggests that patients treated with DEE-TACE + SCT have the best oncological outcomes and greatest potential to be converted for resection.     

Psychological factors and future performance of football players: A systematic review with meta-analysis

ObjectivesThis systematic review had 3 key objectives: (1) to investigate whether psychological factors were associated with future football performance (e.g., progression to professional football, better game statistics during the next season); (2) to critically review the methodological approaches used in the included studies and summarize the evidence for the current research question; (3) to provide guidelines for future studies.DesignSystematic review.MethodsElectronic databases (SPORTDiscus, PubMed and PsycINFO) and previously published systematic and scoping reviews were searched. Only prospective studies were considered for inclusion.ResultsEleven published studies that reported 39 effect sizes were included. Psychological factors; task orientation, task-oriented coping strategies and perceptual-cognitive functions had small effects on future performance in football (ds = 0.20–0.29). Due to high risk of bias there were low certainty of evidence for psychological factors relationship with future football performance.ConclusionsPsychological factors investigated showed small effects on future football performance, however, there was overall uncertainty in this evidence due to various sources of bias in the included studies. Therefore psychological factors cannot be used as a sole deciding factor in player recruitment, retention, release strategies, however it would appear appropriate to include these in the overall decision-making process. Future, studies with more appropriate and robust research designs are urgently needed to provide more certainty around their actual role.     

Intraoperative high-dose-rate brachytherapy using dose painting technique: Evaluation of safety and preliminary clinical outcomes

PurposeIntraoperative radiation therapy (IORT) allows delivery of tumoricidal doses of radiation to areas of potential residual microscopic disease while minimizing doses to normal tissues. IORT using high-dose-rate (HDR) brachytherapy allows dose modulation and delivery of concomitant boosts to high-risk areas. This study describes a novel technique of HDR-IORT with dose painting (DP) (HDR-IORT-DP) and evaluates the clinical outcomes.Methods and MaterialsSixteen patients with recurrent cancers received HDR-IORT-DP at the time of radical resection. Of these patients, 13 had colorectal cancer, 2 had head and neck cancer, and 1 had a gynecologic malignancy. All received external beam radiation previously. Negative margin (R0) was obtained in 12 patients (75%) and microscopically positive margins (R1) in 4 patients (25%).ResultsThe median total target and boost area were 45 and 8.5 cm², and HDR-IORT and boost dose were 1500 and 1750 cGy, respectively. Median followup was 14.9 months. The 2-year local control and overall survival were 80% and 20%, respectively. Eleven patients (69%) developed distant metastasis and were deceased at the time of the last followup. A total of 13 patients (19%) developed Grade 3 toxicity related to HDR-IORT; no grade 4+ toxicities were observed.ConclusionsHDR-IORT-DP technique is feasible, safe, and allows for dose escalation in locally advanced or recurrent previously irradiated tumors. To our knowledge, this is the first clinical report on HDR-IORT-DP. Further studies are warranted to evaluate efficacy in a larger patient cohort. Local control was encouraging in our patients.     

Vaginal cuff brachytherapy in the adjuvant setting for patients with high-risk early-stage cervical cancer

PurposeTo evaluate local control and survival of high-risk patients with early-stage cervical cancer submitted or not to vaginal cuff brachytherapy in the postoperative setting.Methods and MaterialsIn this retrospective cohort of patients treated from 2010 to 2017, patients were eligible if they had confirmed histological diagnosis of cervical cancer treated with surgery and adjuvant radiotherapy with or without chemotherapy. Vaginal cuff brachytherapy (VCB) was indicated according to the radiation oncologist discretion.ResultsSeventy-nine patients were selected, with a median age at diagnosis of 47.5 years (26–77). Brachytherapy was delivered to 59 patients (74.7%). There were no significant differences between the VCB and the no-VCB groups. A total of 13 (16.5%) patients presented one or more events, 5 (25%) and 8 (13.5%) events in the no-VCB and VCB group, respectively. Most recurrences were pelvic and/or vaginal: 7/20 (35%) in the no-VCB group and 9/59 (10.2%) in the VCB group. There were eight systemic relapses with eight deaths. With a median followup of 45 months, mean overall survival and disease-free survival were, respectively, 85.1 and 83.8 months. No variables were correlated with overall survival. The only factor positively correlated to disease-free survival was VCB, with a mean of 86.9 and 68.4 months for patients who did and did not receive brachytherapy, respectively (p = 0.043). Vaginal recurrence was lower in the brachytherapy group, but with no statistical significance (p = 0.065).ConclusionVCB was associated with a reduced recurrence rate in the postoperative setting of high-risk patients with early-stage cervical cancer.