Single-fraction brachytherapy as monotherapy for early-stage prostate cancer: The UCSF experience

PurposeHigh-dose-rate (HDR) brachytherapy as monotherapy is an effective treatment option for localized prostate cancer, but experience with single-fraction brachytherapy is limited by studies with small sample size. We report a large single-institution experience with single-fraction HDR brachytherapy as monotherapy for early-stage prostate cancer.Methods and MaterialsRetrospective chart review was performed for men treated with HDR brachytherapy as monotherapy for low- to intermediate-risk prostate cancer. Competing risk analyses were performed to estimate subdistribution hazard ratio and cumulative incidence of biochemical recurrence (BCR) and prostate cancer–specific mortality.ResultsWe identified 124 men with a median followup of 2.2 years (interquartile range 25th to 75th percentile: 1.8–3). Overall, 21.0% of patients (n = 26) were low risk, 44.4% (n = 55) were favorable intermediate risk, and 34.7% (n = 43) were unfavorable intermediate risk. At 2 years, the cumulative incidence of BCR was 3.5%: 0% for low risk, 4.0% for favorable intermediate risk patients, and 4.5% for unfavorable intermediate risk patients. In total, 12 BCRs were observed (9.7%) and approximately half occurred after median followup of 2.2 years. Compared with low-risk and favorable intermediate-risk disease, unfavorable intermediate-risk disease was significantly associated with BCR (subdistribution hazard ratio: 3.6, 95% CI: 1.1 to 11.1, p = 0.03). Prostate cancer–specific mortality was 0%. No patient experienced Grade 3 or higher acute or late genitourinary toxicity.ConclusionsSingle-fraction brachytherapy for early-stage prostate cancer was safe with promising short-term disease control rates, especially for low-risk patients. Longer term followup is needed as we observed an overall BCR rate of 9.7%.     

High-dose-rate brachytherapy with or without intensity modulated radiation therapy as salvage treatment for an isolated,gross local recurrence of prostate cancer post-prostatectomy

PurposeTo evaluate the use of high-dose-rate (HDR) brachytherapy ± intensity modulated radiation therapy (IMRT) as salvage therapy for patients with an isolated, gross local recurrence of prostate cancer after radical prostatectomy.Methods and MaterialsBetween October 2009 and May 2013, the authors treated six patients with salvage iridium-192 HDR brachytherapy ± IMRT for biopsy-proven, recurrent prostate cancer post-prostatectomy. In each patient, a pelvic MRI scan or CT scan demonstrated a nodule (range 1.6, 4.7 cm) in the prostate bed. Although prostate-specific antigen values were 0.2–9.5 ng/mL at the time of salvage brachytherapy, there was no pelvic adenopathy on CT or MRI scan, and a bone scan was negative in all cases. Five patients were treated with IMRT to 4500–5040 cGy in 25–28 fractions to the prostate bed followed by two 950 cGy HDR brachytherapy fractions separated by 1–2 weeks. A sixth patient underwent HDR brachytherapy monotherapy consisting of 3800 cGy in four fractions over 3 days. Toxicities were graded according to the Common Terminology Criteria for Adverse Events, version 4.0.ResultsMedian followup was 9 months (range 3, 40 months). All six patients have been free of androgen deprivation therapy and have an undetectable prostate-specific antigen. One patient developed late Grade 2 urinary incontinence. There was no late grade ≥2 gastrointestinal toxicity.ConclusionsHDR brachytherapy ± IMRT is a safe and effective salvage therapy option for an isolated, gross local recurrence of prostate cancer after radical prostatectomy and merits further study.     

Radioactive seed migration after transperineal interstitial prostate brachytherapy and associated development of small-cell lung cancer

PurposeWe report a case of lung carcinoma developing in the location of a migrated prostate brachytherapy seed.Methods and MaterialsA 57-year-old male nonsmoker was originally diagnosed with prostate adenocarcinoma Group IIB in October 1999. Treatment was completed at an outside local hospital and consisted of hormone suppression, pelvic external beam radiation, and transperineal interstitial permanent prostate brachytherapy with loose iodine-125 seeds.ResultsThe treatment was unremarkable for any complications, and immediate postimplant evaluation did not reveal any loose seeds. The patient remained clinically without evidence of disease and was asymptomatic until an isolated episode of hematuria in December 2009. Radiographic evaluation noted an incidental right lower lobe lung mass with a 4-mm hyperdensity slightly off-center. Biopsy confirmed Stage IB limited-stage small-cell lung cancer, and he underwent thoracic radiation with concurrent systemic chemotherapy. The mass remained mildly avid on a positron emission tomographic scan after treatment, and he underwent surgical evaluation with final pathology demonstrating no residual tumor but a metal rod-like implant consistent with a migrated radioactive brachytherapy seed.ConclusionsTo our knowledge, this is the first case of a long-term adverse sequela seen in the location of a migrated brachytherapy seed. Although reported incidence of pulmonary seed emboli remains low with little measurable consequence on pulmonary function, we must appreciate that a theoretical risk for secondary malignancy remains not only locally within the periprostatic region but also at any site of seed migration.     

Prostate brachytherapy seed embolization to the right renal artery

PurposeWe report three cases of seed embolization to the right renal artery after iodine-125 (I-125) transperineal interstitial permanent prostate brachytherapy.Methods and materialsCase 1: A 65-year-old man presented with right flank and back pain less than 4 months after prostatic seed implantation. CT evaluation for renal stone showed a seed embedded in the lower aspect of the right kidney. Case 2: A 73-year-old man complained of painless hematuria 3 years after prostatic seed brachytherapy. CT and subsequent abdominal angiography showed a seed embolization to a lower branch of the right renal artery. Case 3: An 84-year-old man presented with gross hematuria 7 months after prostatic seed implantation. Excretory urogram and subsequent CT demonstrated the right lower renal seed migration.ResultsProstatic seed embolization to the right renal artery may cause pain and hematuria. This pattern of seed migration may be easily overlooked by imagers because it mimics renal lithiasis on cross-sectional imaging. Knowledge of prior history of permanent interstitial prostate brachytherapy and careful radiologic interpretation may help to achieve the correct diagnosis of rare renal seed migration.ConclusionsWe present an additional atypical site of brachytherapy seed relocation in the right renal artery in 3 patients. This type of migration is probably secondary to pulmonary arteriovenous malformation or right-to-left cardiac shunts. Awareness of the propensity of seeds to dislodge and vigilance in imaging interpretation of prostatic brachytherapy recipients are necessary for the correct diagnosis of seed embolization.     

Prostatic Artery Embolization for Control of Gross Hematuria in Patients with Benign Prostatic Hyperplasia: A Single-Center Retrospective Study in 20 Patients

PurposeTo evaluate the efficacy and safety of prostatic artery embolization (PAE) performed to treat gross hematuria secondary to benign prostatic hyperplasia (BPH).Materials and MethodsBetween February 2014 and December 2017, 20 patients with gross hematuria secondary to BPH refractory to medical treatment underwent PAE in our institution. Technical success was defined as bilateral PAE. International Prostate Symptom Score (IPSS), quality of life (QoL), and clinical review were assessed before PAE and at 3 and 12 months after procedure. Short- and medium-term clinical successes were defined as resolution of gross hematuria with no recurrence at 3 and 12 months, respectively.ResultsTechnical success rate was 100%. No major adverse events were recorded. Minor complications included gluteal pain, nausea, and fever in 7 patients. At 3 months, there were improvements in IPSS (21.1 ± 6.6 to 9.8 ± 4.7, P < .001) and QoL (5.1 ± 1.7 to 2.4 ± 1.3, P < .001). At 12 months, there were improvements in IPSS (8.1 ± 2.5, P < .001) and QoL (2.1 ± 1.0, P < .001). At 3 months, recurrent hematuria was reported in 3 of 20 patients (85% short-term clinical success rate). One of the remaining 17 patients had developed recurrent hematuria by 12 months (80% medium-term clinical success rate).ConclusionsPAE is a safe and effective means of treating gross hematuria caused by BPH refractory to medical treatment. PAE offers a reasonable option for such patients who are not suitable for surgical therapy.     

Comparison of intracavitary brachytherapy and stereotactic body radiotherapy dose distribution for cervical cancer

PurposeTo compare the dose distribution characteristics of stereotactic body radiotherapy (SBRT) with intracavitary high-dose-rate (HDR) brachytherapy in patients with cervical carcinoma.Methods and MaterialsHDR intracavitary brachytherapy treatment plans for 11 women with cervical carcinoma were evaluated in this analysis. The total HDR brachytherapy dose was 28 Gy given in four fractions. HDR brachytherapy was delivered with the microSelectron HDR therapy unit (Nucletron B. V., Veenendaal, The Netherlands). SBRT plans for each patient were generated with MultiPlan for CyberKnife Robotic Radiosurgery System (Accuray Inc., Sunnyvale, CA). The dose distributions, dose–volume histograms, and maximum dose points of the target and critical organs were recorded for both plans.ResultsSBRT yielded significantly better target coverage; the median target coverage for the 100% isodose line was 50.7% for HDR brachytherapy plans, whereas it was 99.1% for SBRT plans. The dose distributions for critical organs were similar in both types of plans. The exceptions were the 25% isodose being significantly better in brachytherapy plans for rectum, and the 100% isodose exposure being higher in brachytherapy plans for rectum, bladder, and sigmoid colon. Some significant differences were also found in maximum doses received by a 2-cc volume of bladder in favor of SBRT plans. In addition, maximum bone marrow doses were significantly higher in SBRT plans.ConclusionSBRT plans achieved better target coverage and better dose distributions to critical organs except bone marrow compared with HDR brachytherapy plans in patients with locally advanced cervical cancer.     

Toward four-dimensional image-guided adaptive brachytherapy in locally recurrent endometrial cancer

PurposeTo evaluate clinical outcome and feasibility of a four-dimensional image-guided adaptive brachytherapy concept in patients with locally recurrent endometrial cancer.Methods and MaterialsForty-three patients with locally recurrent endometrial cancer were included. Treatment consisted of conformal external beam radiotherapy followed by a boost using pulsed-dose-rate brachytherapy (BT). Large tumors were treated with MRI-guided interstitial BT. Small tumors were treated with CT-guided intracavitary BT. The planning aim (total external beam radiotherapy and BT) for high-risk clinical target volume was D₉₀ > 80 Gy, whereas constraints for organs at risk were D_2cc ≤ 90 Gy for bladder and D_2cc ≤ 70 Gy for rectum, sigmoid, and bowel in terms of equivalent dose in 2 Gy fractions.ResultsMedian high-risk clinical target volume was 18 cm³ (range, 0–91). D₉₀ was 82 Gy (range, 77–88). D_2cc to bladder, rectum, and sigmoid were 67 Gy (range, 50–81), 67 Gy (range, 51–77), and 55 Gy (range, 44–68), respectively. Median followup was 30 months (6–88). Two-year local control rate was 92% (standard error [SE], 5). Disease-free survival rate and overall survival rate was 59% (SE, 8) and 78% (SE, 7), respectively. Patients with low- to intermediate-risk for recurrence had a 2-year disease-free survival rate of 72% (SE, 9) compared with 42% (SE, 12) in patients with high risk for recurrence (p = 0.04). Late morbidity Grade 3 was recorded in 5 (12%) patients.ConclusionsFour-dimensional image-guided adaptive brachytherapy is feasible in locally recurrent endometrial cancer. Local control rate is good. Systemic control remains a problem in patients with high risk for recurrence.     

局部晚期宫颈癌腔内放疗联合组织间插植的剂量学研究

目的 比较局部晚期宫颈癌单纯腔内放疗与腔内联合组织间插植放疗的剂量学差异。方法 2016年5月—2017年3月局部晚期宫颈癌患者共35例,均行根治性放疗,治疗方法为外照射+腔内联合组织间插植放疗。调强放射治疗处方剂量为46.8~50.4 Gy/26~28次,1.8 Gy/次。腔内联合组织间插植放疗剂量为7 Gy/次,1次/周,共4次。同一患者首先置入三管式后装放疗施源器,采集CT图像制定治疗计划,取出三管式施源器后,置入宫腔管并植入插植针,再次采集图像制定放疗计划。分别评价比较两组计划中靶区及危及器官的受照剂量差别。结果 共制定212次后装放疗计划,其中单纯腔内治疗计划106例,腔内联合组织间插植治疗计划106例。腔内联合组织间插植放疗组计划较单纯腔内放疗组的靶区剂量明显升高,高危临床靶区（CTV）的D₉₀、中危CTV的D₉₀均显著增高（t=-6.01、-2.73,P<0.05）,膀胱、直肠、乙状结肠的D_{2 cm³}显著降低（t=3.07、4.52、2.91,P<0.05）。结论 局部晚期宫颈癌应用腔内联合插植放疗可以明显提高靶区剂量,并降低危及器官膀胱、直肠和乙状结肠的受照剂量。     

Impact of CT-based brachytherapy in elderly patients with cervical cancer

PurposeThree-dimensional image-guided brachytherapy (3D-IGBT) has become the standard therapy for patients with cervical cancer. However, in this population, the impact of 3D-IGBT in elderly individuals remains unknown. This study assessed the efficacy of 3D-IGBT for elderly patients with cervical cancer.Methods and MaterialsWe performed a retrospective chart review of 105 consecutive patients with cervical squamous cell carcinoma aged ≥70 years who received radiotherapy alone between January 2001 and September 2014. All patients were treated with external beam radiotherapy and high-dose-rate intracavitary brachytherapy. We assessed the treatment outcomes in all patients. We then compared outcomes between two groups: patients treated by changing the Point A dose at brachytherapy (Group A, n = 71) and those treated with 3D-IGBT at least twice (Group B, n = 34).ResultsThe median followup period was 59 (range, 6–203) months; the median age was 77 years. The 5-year local control and cause-specific survival rates were 89% and 78%, respectively. The 5-year cumulative rates of late toxicities of the rectum and bladder of Grade ≥3 were 2.0% and 4.2%, respectively. No statistically significant differences were observed in the local control and cause-specific survival rates, or in the incidence of rectal toxicities between groups. The 3-year cumulative rates of urinary toxicity of Grade ≥1 were 20.4% and 6.9% in Group A and Group B, respectively (p = 0.035).ConclusionIn elderly patients with cervical cancer, 3D-IGBT could be performed safely and effectively and contributed to decreasing urinary toxicity incidence rates.     

Permanent seed brachytherapy for locally recurrent prostate cancer after radical prostatectomy: A case report and review of the literature

PurposeTo describe the management of a patient with locally recurrent prostate cancer in the prostate bed, 10 years after a radical prostatectomy.Methods and MaterialsA 71-year-old man had a radical prostatectomy for a Gleason 7 clinical T2a carcinoma of the prostate in 2000. Final pathologic stage was pT3a pN0. Postoperatively his prostate-specific antigen was undetectable, but by 2008 it was 1.0 ng/mL and in 2011 it reached to 1.43 ng/mL. He was referred for consideration of salvage radiotherapy. Staging workup was negative but transrectal ultrasound revealed a 15 cc recurrence in the prostate bed. A combination of external beam radiation therapy (4600/23/4.5 weeks to the pelvis) and a brachytherapy boost (115 Gy) was selected for definitive management. Androgen ablation was not used.ResultsThe treatment was well tolerated. The brachytherapy boost was planned in a similar fashion to a de novo implant for an intact prostate. The postimplant dosimetry was evaluated using magnetic resonance imaging-computed tomography (MR–CT) fusion and appeared satisfactory. Acute toxicity was minimal. Six months after brachytherapy, the prostate-specific antigen had fallen from 1.43 to 0.05 ng/mL.ConclusionsDose escalation with combined external beam and brachytherapy may be feasible if recurrent disease can be visualized using transrectal ultrasound and encompassed in an implanted volume. Although longer followup and a larger series of patients are required to demonstrate safety and efficacy, consideration should be given this approach.     

Cost-effectiveness of prostate boost with high-dose-rate brachytherapy versus intensity-modulated radiation therapy in the treatment of intermediate-high risk prostate cancer

PurposeThe recently published ASCENDE-RT randomized clinical trial demonstrated improved biochemical control, albeit with increased toxicity, for a prostate boost with brachytherapy versus external beam radiation therapy alone in patients with intermediate-high risk prostate cancer. In this study, we investigated the cost-effectiveness of these two modalities in the treatment of intermediate-high risk prostate cancer.Methods and materialsA multistate Markov model was created to model a patient with intermediate-high risk prostate cancer. The two treatment options modeled were (1) 23 fractions of intensity-modulated radiation therapy (IMRT) and two fractions of high-dose-rate prostate brachytherapy (brachytherapy boost) and (2) 44 fractions of IMRT (IMRT alone). Each patient received 1 year of hormone therapy, per the ASCENDE-RT protocol. Model assumptions, including clinical outcomes, toxicity, and utilities were derived from the medical literature. Costs of radiation therapy were estimated using Medicare reimbursement data.ResultsThe estimated expected lifetime cost of brachytherapy boost was $68,696, compared to $114,944 for IMRT alone. Brachytherapy boost significantly lowered expected lifetime treatment costs because it decreased the incidence of metastatic castration-resistant prostate cancer, cutting the use of expensive targeted therapy for metastatic castration-resistant prostate cancer. Brachytherapy boost had an expected quality-adjusted life years of 10.8 years, compared to 9.3 years for IMRT alone. One-way sensitivity analyses of our results found brachytherapy boost to be cost-effective over a wide range of cost, utility, and cancer progression rate assumptions.ConclusionsIMRT with high-dose-rate brachytherapy boost is a cost-effective treatment for intermediate-high risk prostate cancer compared to IMRT alone.     

Novel use of ViewRay MRI guidance for high-dose-rate brachytherapy in the treatment of cervical cancer

PurposeTo characterize image quality and feasibility of using ViewRay MRI (VR)–guided brachytherapy planning for cervical cancer.Methods and MaterialsCervical cancer patients receiving intracavitary brachytherapy with tandem and ovoids, planned using 0.35T VR MRI at our institution, were included in this series. The high-risk clinical target volume (HR-CTV), visible gross tumor volume, bladder, sigmoid, bowel, and rectum contours for each fraction of brachytherapy were evaluated for dosimetric parameters. Typically, five brachytherapy treatments were planned using the T2 sequence on diagnostic MRI for the first and third fractions, and a noncontrast true fast imaging with steady-state precession sequence on VR or CT scan for the remaining fractions. Most patients received 5.5 Gy × 5 fractions using high-dose-rate Ir-192 following 45 Gy of whole-pelvis radiotherapy. The plan was initiated at 5.5 Gy to point A and subsequently optimized and prescribed to the HR-CTV. The goal equivalent dose in 2 Gy fractions for the combined external beam and brachytherapy dose was 85 Gy. Soft-tissue visualization using contrast-to-noise ratios to distinguish normal tissues from tumor at their interface was compared between diagnostic MRI, CT, and VR.ResultsOne hundred and forty-two fractions of intracavitary brachytherapy were performed from April 2015 to January 2017 on 29 cervical cancer patients, ranging from stages IB1 to IVA. The median HR-CTV was 27.78 cc, with median D₉₀ HR-CTV of 6.1 Gy. The median time from instrument placement to start of treatment using VR was 65 min (scan time 2 min), compared to 105 min using diagnostic MRI (scan time 11 min) (t-test, p < 0.01). The contrast-to-noise ratio of tumor to cervix in both diagnostic MRI and VR had significantly higher values compared to CT (ANOVA and t-tests, p < 0.01).ConclusionsWe report the first clinical use of VR-guided brachytherapy. Time to treatment using this approach was shorter compared to diagnostic MRI. VR also provided significant advantage in visualizing the tumor and cervix compared to CT. This presents a feasible and reliable manner to image and plan gynecologic brachytherapy.     

Role of brachytherapy in post-operative cervical cancer patients with risk factors other than positive stump

OBJECTIVEThis study aimed to determine the effectiveness of brachytherapy in post-operative cervical cancer patients with risk factors other than positive stump, and to identify the candidates most likely to benefit.METHODSNewly diagnosed, non-metastatic cervical cancer patients treated in our hospital between January 2012 and November 2015 were retrospectively reviewed. Early stage patients receiving radical surgery and needing adjuvant external radiotherapy were included, but those with positive stump were excluded. All patients received external radiotherapy. They were divided into two groups: one group received vaginal brachytherapy and the other did not. The 5-year local-regional recurrence free survival (LRRFS) and overall survival (OS) rates in the two groups were compared.RESULTSTwo hundred and twenty-five patients were included in this study; while 99 received brachytherapy, 126 did not. The brachytherapy group had significantly superior 5-year LRRFS (87.7% vs. 72.5%, p = 0.004), but did not show a significant overall survival benefit (78.4% vs. 75.3%, p = 0.055). In multivariate analysis, brachytherapy, pathological type, high-risk factors, duration of radiotherapy, and transfusion were independent prognostic factors for 5-year LRRFS. In stratified analysis, the brachytherapy group showed superior LRRFS in those meeting Sedlis criteria (p = 0.017).CONCLUSIONThe combination of external beam radiation therapy and brachytherapy can improve LRRFS in post-operative cervical cancer patients with risk factors other than positive stump. Therefore, brachytherapy should be considered for these patients.     

Salvage low-dose-rate brachytherapy for local recurrences after prostatectomy and adjuvant or salvage external beam irradiation: Feasibility study on five patients and literature review

PurposeTo assess the feasibility and tumor outcome of re-irradiation with low-dose-rate brachytherapy for macroscopic local recurrences after radical prostatectomy (RP) followed by adjuvant or salvage external beam radiation therapy (EBRT).Methods and MaterialsBetween 2011 and 2018, five men with histologically proven local failure within the prostate (4) or seminal vesicle bed (1) after RP and adjuvant or salvage EBRT (median dose: 67.5 Gy) underwent a salvage brachytherapy (S-BT). The median delay after EBRT was 86 months (range 75–234). Two patients were castration-resistant at the time of S-BT. The gross tumor volume was defined on a multiparametric MRI and transrectal US imaging. Echo-guided transperineal implants of Iodine-125 seeds were optimized with a per-operative dosimetry and delivered with the seed-selectron.ResultsA high conformity was achieved with a high dose to the CTV (D_95% > 145 Gy in all but one) and very low dose to the rectum, urethra, and bladder. With a median followup of 21 months, all but one patient experienced nodes and/or bone metastases. Local control was achieved in 3/4 of evaluable patients (local failure distant to the treated volume in one). To date, no Grade 2 or more late toxicities were observed.ConclusionFor selected patients, focal local recurrence brachytherapy after PR and EBRT appears technically feasible and safe, but the efficacy remains uncertain as the majority of patients quickly relapsed at other sites. Large prospective studies are still required to better select patients who will benefit from this strategy.     

宫颈癌二维近距离后装治疗中危及器官参考点剂量与三维体积剂量的相关性研究

目的 利用宫颈癌二维近距离后装治疗中危及器官（OARs）点剂量预测其三维体积剂量,评估在特定条件下,二维计划OARs体积剂量能否满足三维后装剂量限值要求。方法 回顾性分析基于CT图像的10例宫颈癌患者近距离后装治疗计划,将处方参考点剂量定为600 cGy,膀胱和直肠参考点剂量<360 cGy,设计并优化得到二维后装治疗计划。采用Pearson相关分析法对膀胱、直肠参考点剂量及OARs体积受量做相关性分析,利用线性回归方法得出膀胱、直肠参考点与其体积剂量的线性方程。结果 膀胱、直肠参考点剂量分别与其D_{1 cm³}、D_{2 cm³}、D_{5 cm³}和平均剂量显著正相关（r=0.559~0.668,P<0.05）;膀胱、直肠参考点剂量分别是其D_{2 cm³}的1.404和1.181倍;内外照射完成后膀胱、直肠D_{2 cm³}的相当于200 cGy分次等效生物剂量（EQD2）分别为8 410.0和6 827.0 cGy,均低于二者体积剂量限值。结论 利用膀胱、直肠参考点剂量能在一定程度上预测其体积剂量,对于满足膀胱、直肠参考点剂量低于处方剂量60%二维近距离后装计划,可将膀胱、直肠体积受量控制在相对安全的剂量范围内。而由于缺乏对小肠、乙状结肠剂量检测,二维后装计划在临床使用上仍然具有很大局限性。     

Low-Dose-Rate versus High-Dose-Rate intracavitary brachytherapy in cervical cancer - Final Results of a Phase III randomized trial

PURPOSEIntracavitary brachytherapy using High-Dose-Rate (HDR) and Low-dose-rate (LDR) in cervical cancer has been utilized. We report the long-term final results of a large randomized trial in terms of toxicities and efficacy.METHODS AND MATERIALSBetween 1996 to 2005, 816 patients were randomized to LDR (n = 441 patients) or HDR brachytherapy (n = 369 patients) stratified by FIGO Stage grouping. Patients with Stage I-II received external irradiation of 40 Gy in 20 fractions (with midline block (MLB)) followed by either 2 LDR Intracavitary applications of 30 Gy to point A (2–3 weeks apart) or 5 HDR Intracavitary applications of 7 Gy to point A once weekly. Patients with Stage III received 50 Gy in 25 fractions (with MLB after 40 Gy) followed by either one application of LDR 30 Gy to point A or three applications of HDR 7 Gy to point A once weekly.RESULTSWith a median follow-up was 64 months (interquartile range [IQR]: 21 - 111), moderate to severe rectal and bladder complications were higher in LDR arm as compared to HDR arm (9.7% vs. 3.6%; p = 0.02) and (10.5% vs. 5.5%; p = 0.06) for Stage I-II. No difference in rectal or bladder complications for Stage III patients. Disease free and overall survivals were similar in both the arms for all stages.CONCLUSIONSHDR intracavitary brachytherapy with 7 Gy per fraction weekly is superior to LDR in terms of late rectal and bladder complications. Local control rates and survivals are similar irrespective of stages.     

Concurrent chemoradiation for cervical cancer: Comparison of LDR and HDR brachytherapy

PurposeTo compare clinical outcomes between low-dose-rate (LDR) brachytherapy and high-dose-rate (HDR) brachytherapy for cervical cancer patients.Methods and MaterialsAll consecutive newly diagnosed cervical cancer patients undergoing pretreatment 18-fluorodeoxyglucose positron emission tomography imaging and treated with curative-intent definitive chemoradiation from 1997 to 2016 at a U.S. academic center were included. Brachytherapy boost was LDR or HDR 2D treatment planning from 1997 to 2005 and HDR with MR-based 3D planning from 2005 to 2016. Local control (LC), cancer-specific survival (CSS), and late bowel/bladder complications were evaluated.ResultsTumor stages were International Federation of Gynecology and Obstetrics IB1-IIB (n = 457; 75%) and III-IVA (n = 152; 25%). Brachytherapy was LDR for 104 patients and HDR for 505 patients. Concurrent weekly cisplatin was administered to 536 patients (88%). With median followup of 9.4 years, there was no difference in LC (p = 0.24) or CSS (p = 0.50) between LDR and HDR brachytherapy. Cox multivariable regression showed that only International Federation of Gynecology and Obstetrics stage III-IVA (HR=2.4, p = 0.004) was associated with worse LC. A propensity-matched cohort (90 LDR vs. 90 HDR) was created, and the 5-year LC rates were 88% LDR and 82% HDR, p = 0.26; 5-year CSS rates were 66% LDR and 58% HDR, p = 0.19; 5-year grade ≥3 bowel/bladder toxicities were 23% LDR and 16% HDR, p = 0.44. For all patients, the 5-year late toxicity in stage III-IVA patients was higher with LDR 47% vs. HDR 15%, p = 0.03, with no difference in LC, 86% and 75%, respectively (p = 0.09).ConclusionsThere was no difference in LC with either LDR or HDR brachytherapy. The late complication rate was reduced with HDR and 3D-planned brachytherapy compared to LDR and 2D-planned brachytherapy.     

Image-guided brachytherapy following external-beam radiation therapy for patients with inoperable endometrial cancer

ObjectiveTo investigate the outcomes of definitive external-beam radiation therapy (EBRT) plus image-guided brachytherapy (IGBT) in patients with endometrial cancer (EC) unsuitable for surgery.MethodsA total of 50 patients with inoperable EC were included. The patients received EBRT in a median dose of 45 Gy to the pelvis over 5 weeks. Thereafter, the patients received brachytherapy using tandem and ovoid applicators. High-risk clinical target volume (HR-CTV) and gross tumor volume in brachytherapy (GTVp) were defined by the assistance of patients’ pre-IGBT magnetic resonance imaging.ResultsThe medical records of the 50 patients were analyzed. The main causes of inoperability were anesthesia contraindications, namely medical comorbidities and obesity. The median cumulative D90s (the minimum dose delivered to 90% of the volume) in EQD2 (equivalent dose in 2-Gy fractions) to the HR-CTV and GTVp were 72.9 Gy10 (range, 64.9 to 80.3) and 166.2 Gy10 (range, 123.0 to 189.8), respectively. Over a median follow-up period of 27 months, 8 of the patients died of cancer. The 2-year overall and cancer-specific survival rates were 75% and 83%, respectively. The cumulative incidences of pelvic and distant failure were 4% (n = 2) and 16% (n = 8), respectively. Gastrointestinal complications of grade 2 or above were noted in 2 patients (4%), and a grade 2 genitourinary complication was noted in one.ConclusionsFor patients with inoperable EC, EBRT followed by IGBT is an effective approach for achieving high local control without a high risk of complications.     

Evaluation of an MR-only interstitial gynecologic brachytherapy workflow using MR-line marker for catheter reconstruction

PurposeMagnetic resonance imaging (MRI) offers excellent soft-tissue contrast enabling the contouring of targets and organs at risk (OARs) during gynecological interstitial brachytherapy procedure. Despite its benefit, one of the main challenges toward MRI-only workflows is that the implanted catheters are not reliably visualized on MR images. This study aims to evaluate the feasibility of MR-only workflow using an in-house MR line marker during interstitial gynecological high-dose-rate (HDR) brachytherapy.Methods and MaterialsTen patients diagnosed with locally advanced cervical cancer treated with HDR brachytherapy were included in this study. The hybrid CT/MR-treated plan was used as the study reference plan. Five users manually reconstructed the catheter's path on MR images (3D T1- and T2-weighted). Subsequently, the dwell positions from the users’ plans were superimposed on the reference plans to evaluate the dosimetric impact of the using MR-only for catheter reconstruction in comparison with hybrid CT/MR approach. Variability of dwell positions between users and reconstruction time was also evaluated.ResultsMore than 96.90% of catheter reconstruction variations were < 2 mm. No statistical differences were reported between MR-only and hybrid CT/MR in gross tumor volume D₉₈ and high-risk clinical target volume D₉₀, respectively. For the OARs (bladder, sigmoid, rectum, and bowel), no significant changes were observed in any dose metrics between MR-only and hybrid CT/MR. The average reconstruction time was 51 ± 10 minutes across all ten patients.ConclusionThe feasibility of MR-only workflow using MR line marker during interstitial gynecological HDR brachytherapy has been validated in this study. The results show that the MR-only workflow is equivalent to the conventional hybrid CT/MR approach in terms of gross tumor volume and high-risk clinical target volume coverage and respecting of OARs dose limits.     

Impact of suboptimal tandem implantation on local control and complications in intracavitary brachytherapy for cervix cancer

PURPOSECorrect tandem implantation for cervix cancer intracavitary brachytherapy may be challenging. We investigated whether suboptimal implantation can be related to patient and disease characteristics and may result in subsequent underutilization of brachytherapy in cervical cancer.METHODS AND MATERIALSConsecutive cervix cancer patients referred for intracavitary brachytherapy after external beam radiation therapy performed in several general hospitals from 2013 to 2017 were included.ResultsIn 172 patients having 301 procedures, 95 implantations were suboptimal (15% inadequate tandem insertions, 10% subserosal insertion, and 6% uterine perforation on postimplant CT scan). Risk factors were age, myometrium invasion, and uterine retroversion. Median followup was 21 months. Three-year local control and survival rates were 72% and 85%, respectively. Forty-seven patients (27%) failed to receive brachytherapy. Failure to perform brachytherapy was associated with poorer local control (OR = 0.34 [0.17–0.67], p = 0.001). By contrast, suboptimal implantation did not increase local failure or toxicity rates in patients undergoing brachytherapy. No peritoneal carcinomatosis occurred after uterine perforation in our cohort.CONCLUSIONSSuboptimal implantation was frequent. In the absence of image guidance during implantation, conversion to other treatment modalities (including external beam radiation therapy) due to insertion difficulties resulted in worse local control. With optimization, however, suboptimal brachytherapy implantation did not result in suboptimal dose coverage or poorer local control. Failure to perform a brachytherapy boost correlates with increased local failure risk in patients with cervix cancer, whereas tandem malposition does not. Real-time intraoperative ultrasound guidance may be useful to reduce uterine perforation rates and thus increase brachytherapy use.