Upfront radiotherapy with brachytherapy for medically inoperable and unresectable patients with high-risk endometrial cancer

ObjectivesComprehensive surgery with adjuvant therapy is standard of care for high-risk endometrial cancers, whereas upfront radiotherapy with brachytherapy is indicated for inoperable/unresectable patients, irrespective of risk. We evaluated outcomes for inoperable/unresectable patients with high-risk endometrial cancer (HREC: stage III and/or grade 3) and low-risk endometrial cancer (LREC: stage I/II and grade 1/2) treated with upfront radiotherapy.MethodsTwenty-nine patients with inoperable/unresectable endometrial cancer were treated with upfront radiotherapy at an academic medical center from 2012 to 2019. Cancer-specific survival (CSS), overall survival (OS), and recurrence rates between patients with HREC and LREC were compared.ResultsMedian follow-up was 17.0 months (range 3.7–54.0). Twenty cancers were stage I + II and nine were stage III. Twenty-one cancers were grade 1 + 2 and eight were grade 3. Thirteen patients (45%) had HREC. Twenty-five patients received radiotherapy/chemoradiotherapy for primary treatment, while 4 patients received chemoradiotherapy before surgery. All patients underwent high dose rate brachytherapy (HDR) with 7 receiving HDR alone and 22 receiving external beam radiation and HDR. Two-year CSS was 100% for both HREC and LREC patients (log-rank p = 0.32). There was no OS difference between HREC and LREC patients (2-year: 73% vs. 77%; log-rank p = 0.33). Four HREC and 1 LREC patients recurred with one local recurrence in each group. There were no acute grade ≥3 and two late grade ≥3 gastrointestinal/genitourinary toxicities.ConclusionsUpfront radiotherapy for inoperable/unresectable HREC patients was well tolerated with high local control and CSS rates. Upfront radiotherapy with brachytherapy remains important even for high-risk inoperable and unresectable endometrial cancer patients.     

Evaluating adjacent organ radiation doses from postoperative intracavitary vaginal vault brachytherapy for endometrial cancer

PurposeTo document doses received by critical organs during adjuvant high-dose-rate (HDR) vaginal vault brachytherapy.Methods and MaterialsPatients treated with HDR vaginal vault radiation between January 1, 2009, and January 31, 2012, who had a CT simulation with the treatment cylinder in situ were included. The CT scans were retrospectively reviewed and the rectum, sigmoid, small bowel, and bladder were contoured. Standardized plans treating the upper 4 cm of the vaginal vault were used to deliver a total of 21 Gy (Gy) at 0.5 cm from the apex of the vaginal vault in three fractions.ResultsThere were 41 patients. Median age was 62 years. The median vaginal cylinder diameter was 3 cm. The mean 2cc dose to the rectum, sigmoid, small bowel, and bladder were 5.7, 4.7, 4.0, and 5.6 Gy, respectively. Bladder volume ranged from 67–797 cc. Assuming minimal interfraction organ variation, the equivalent dose in 2 Gy/fraction was extrapolated from data and may be near or beyond organ tolerance for rectum, sigmoid, and small bowel in some cases. Spearman correlation found that increased bladder volume was not associated with adjacent organs at risk dose but may be associated with a trend (p = 0.06) toward increased bladder dose (R = 0.30).ConclusionsThis study describes the dose received by adjacent critical structures during vaginal vault HDR brachytherapy. This is important information for documentation in the rare setting of treatment-related toxicity or recurrence. Bladder volume was not associated with dose to adjacent organs.     

Definitive radiotherapy for medically inoperable early-stage serous and clear cell uterine carcinoma

High-risk, early-stage endometrial cancer is optimally treated by hysterectomy followed by adjuvant radiotherapy. In 1%–9% of cases, the patient is medically unfit or personally unwilling to undergo primary surgery, and definitive radiotherapy may be offered as an alternative definitive therapy. Although several series have reported excellent intrauterine control and disease-specific survival for endometrioid histology, few outcome data are available for patients with serous or clear cell histology treated with radiotherapy alone. We herein describe one case each of early-stage, medically inoperable serous/clear cell histology endometrial cancer treated with definitive radiotherapy. Treatment was well tolerated by both patients, and neither patient required a treatment break. Acute toxicity consisted of self-limited cystitis in one patient. One patient was without evidence of disease progression at 54 months after radiotherapy.     

Targeting the GTV in medically inoperable endometrial cancer using brachytherapy

PURPOSEWe aimed to determine the relationship between gross tumor volume (GTV) dose and tumor control in women with medically inoperable endometrial cancer, and to demonstrate the feasibility of targeting a GTV-focused volume using imaged-guided brachytherapy.METHODS AND MATERIALSAn endometrial cancer database was used to identify patients. Treatment plans were reviewed to determine doses to GTV, clinical target volume (CTV), and OARs. Uterine recurrence-free survival was evaluated as a function of CTV and GTV doses. Brachytherapy was replanned with a goal of GTV D98 EQD₂ ≥ 80 Gy, without regard for coverage of the uninvolved uterus and while respecting OAR dose constraints.RESULTSFifty-four patients were identified. In the delivered plans, GTV D90 EQD₂ ≥ 80 Gy was achieved in 36 (81.8%) patients. Uterine recurrence-free survival was 100% in patients with GTV D90 EQD₂ ≥ 80 Gy and 66.7% in patients with EQD₂ < 80 Gy (p = 0.001). On GTV-only replans, GTV D98 EQD₂ ≥ 80 Gy was achieved in 39 (88.6%) patients. Mean D_2cc was lower for bladder (47.1 Gy vs. 73.0 Gy, p < 0.001), and sigmoid (47.0 Gy vs. 58.0 Gy, p = 0.007) on GTV-only replans compared to delivered plans. Bladder D_2cc was ≥ 80 Gy in 11 (25.0%) delivered plans and four (9.1%) GTV-only replans (p = 0.043). Sigmoid D_2cc was ≥ 65 Gy in 20 (45.4%) delivered plans and 10 (22.7%) GTV-only replans (p = 0.021).CONCLUSIONSOAR dose constraints should be prioritized over CTV coverage if GTV coverage is sufficient. Prospective evaluation of image-guided brachytherapy to a reduced, GTV-focused volume is warranted.     

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.     

乌德勒支施源器用于局部晚期宫颈癌三维近距离放疗的剂量学研究

目的 探讨在使用乌德勒支施源器治疗局部晚期宫颈癌时,不同的管道组合设计与靶区、危及器官（OAR）的剂量关系。方法 调取2017—2018年于河北省沧州中西医结合医院放疗科接受乌德勒支施源器进行近距离治疗的17例局部晚期宫颈癌患者数据,原计划为腔内联合组织间插植近距离放疗（IC/IS）,在原勾画轮廓与照射剂量不变的情况下,去除插植针完成腔内近距离放疗（IC）计划设计,对IC/IS计划和IC计划的剂量参数进行对比分析,并评价加入IS插植针对剂量的影响。结果 IC/IS和IC计划的高危临床靶区（HR-CTV）总的D₉₀分别（88.68±1.84）和（85.54±0.54）Gy,差异具有统计学意义（t=6.200,P<0.05）。此外,在靶区的CI指数上,IC/IS计划的明显高于IC计划（0.58±0.08,0.43±0.05）,差异具有统计学意义（t=1.010,P<0.05）。在两种计划中危及器官（OAR）的受照剂量差异无统计学意义（P>0.05）。结论 对于局部晚期宫颈癌的近距离治疗,使用乌德勒支施源器可满足其处方剂量覆盖,而加入IS针,提高了计划的优化空间,在满足OAR受照剂量限值的基础上,显著提高HR-CTV的受照剂量,且提升了剂量分布均匀性。     

3D打印个体化模具在子宫内膜癌术后三维后装治疗中的剂量学研究

目的 探讨3D打印个体化模具辅助子宫内膜癌术后三维后装治疗中的剂量学优势。方法 回顾性选取宁波大学附属第一医院21例早期子宫内膜癌术后患者的三维后装治疗计划,利用北京科霖众计划系统,在已实施的个体化模具组基础上,为每位患者设计虚拟单通道柱状施源器计划,所有计划均采用三维逆向模拟退火的算法。比较两组计划靶区90%、98%和100%体积接受的最低剂量(D₉₀、D₉₈、D₁₀₀)以及适形指数(CI)、均匀度(HI)、超剂量体积指数(OI);同时,对比两组危及器官膀胱、直肠、小肠和尿道的0.01、1、2以及5 cm³所接受的最大剂量(D_{0.01 cm³}、D_{1 cm³}、D_{2 cm³}以及D_{5 cm³})差异。结果 两组计划都能满足临床需求。在靶区所受剂量方面,两组计划靶区D₉₀、D₉₈、D₁₀₀没有明显差异,但是个体化模具组靶区剂量的CI、HI均优于单通道组靶区,而靶区OI指数小于单通道计划(t=-3.21、-5.99、6.25,P＜0.05)。在危及器官所受剂量方面,个体化模具组膀胱、直肠、尿道所受剂量D_{1 cm³}、D_{2 cm³}和D_{5 cm³}相比单通道组均有明显降低(t=3.18、3.21、3.77、7.97、8.92、10.92、2.54、3.46、4.28,P＜0.05);小肠由于距离靶区比较远,在两组计划中所受剂量差异不明显(P＞0.05)。结论 3D打印个体化模具在子宫内膜癌术后三维近距离治疗中靶区均匀度、适形指数更优,而且膀胱、直肠、尿道所受剂量更低,具有推广价值。     

Image-based intracavitary brachytherapy in the treatment of inoperable uterine cancer: individual dose specification at specific anatomical sites

PURPOSE: With advances in imaging studies, dose specification for uterine cancer can be defined at specific anatomical sites such as the myometrium or the serosal surface rather than at arbitrary points or milligram-hours. This report presents our experience with image-based brachytherapy for inoperable uterine cancer. METHODS AND MATERIALS: Eight patients with organ-confined uterine cancer (2 Stage I GI, 3 Stage I G2, 3 Stage I G3) underwent definitive radiation therapy because of poor medical condition. All the patients underwent a CT or MRI scan of the pelvis before intracavitary application. Based on the size of the uterine cavity, a single-channel intrauterine applicator was selected for a small uterus, and a multiple-channel intrauterine applicator was used for a large uterus. A CT (n=5) or MRI (n=3) scan of the pelvis was performed with the applicator in place in addition to orthogonal pelvic films. Individualized dose specification was 75Gy to the midmyometrium and limited to 50Gy to the serosal surface of the uterus based on imaging information. RESULTS: Four patients with Stage I G1-2 disease had intracavitary brachytherapy alone. Four patients with Stage I G2-3 disease were treated with a combination of external pelvic radiation and intracavitary brachytherapy. Six patients had low-dose-rate brachytherapy, and 2 patients had high-dose-rate brachytherapy. Five patients had single-channel intrauterine brachytherapy, and 3 patients had multiple-channel brachytherapy. Based on the measurements of the uterine wall thickness by the imaging studies, the dose specification was prescribed to 1.5 cm lateral to the central axis of the uterus in 4 patients, 2.0 cm in 3 patients, and 2.5 cm in 1 patient. The medium followup time after radiation treatment was 38 months. Six patients are alive without evidence of disease, and 2 patients died of other causes. All patients had local control without major side effects. CONCLUSIONS: Image-based brachytherapy based on individualized dose specification at specific anatomical sites can be done easily and provides excellent local control for inoperable uterine cancer.     

Time-driven activity-based costing of adjuvant vaginal cuff brachytherapy for uterine cancer in an integrated brachytherapy suite

PurposeAdjuvant vaginal cuff brachytherapy is well tolerated and reduces the risk of local recurrence in endometrial cancer. However, there is provider variation in the number of radiation treatments, which ranges from three to six fractions. Using time-driven activity-based costing, we calculated the cost to deliver three vs six fractions to determine the value of each regimen at our brachytherapy suite with CT-on-rails.Methods and MaterialsProcess maps were created to represent each step from initial consult to completion of therapy. Components of care included personnel, equipment, and consumable supplies. The capacity cost rate was determined for each resource and calculated for each regimen.ResultsThe total direct costs to deliver three- and six-fraction treatment courses were $1,415 and $2,227, respectively. Personnel cost accounted for 63% of overall expenditures. Computed tomography simulation and planning, required for the first fraction, cost $232 for both regimens. Duties of the procedural nurse (scheduling, patient setup, and turnover) consumed the most time at 35% of total personnel minutes.ConclusionsTime-driven activity-based cost analysis revealed a 57% relative increase, but modest absolute increase, in delivery costs for six vs three fractions of brachytherapy at our institution. This current analysis may influence considerations of the relative value between the two treatment schedules, but this methodology should not be interpreted as informative for reimbursement policy evaluation.     

Twice-daily high-dose-rate brachytherapy for medically inoperable uterine cancer

PURPOSE: Medically inoperable patients with uterine cancer pose a therapeutic challenge. We developed a twice-daily schedule of high-dose-rate brachytherapy (HDRB) after a single insertion procedure that required a hospitalization of 3 days. METHODS AND MATERIALS: Favorable patients were offered brachytherapy alone, and all other patients received HDRB after pelvic external beam radiation therapy (EBRT). The prescribed dose was 7Gyx5 fractions and 4-5Gyx4-5 fractions for those treated after EBRT. HDRB was delivered with a b.i.d. schedule (4-6-h interval). RESULTS: Twenty-two patients (21 Stage I, 1 Stage IIB) were deemed medically inoperable. Sixteen patients received EBRT followed by HDRB, and six received HDRB alone. There were no procedural complications or significant acute toxicity. No thromboembolic events occurred within 30 days of the implant. CONCLUSIONS: This technique allows patients to be treated using a single procedure for insertion, with brief hospitalization for twice-daily HDRB.     

The efficacy of hyperbaric oxygen therapy in the treatment of medically refractory soft tissue necrosis after penile brachytherapy

Purpose

Soft tissue necrosis is reported in up to 26% of patients undergoing radiotherapy for penile cancer. Management options include local irrigation, wound debridement, antibiotics, anti-inflammatory medication, and analgesics. Refractory lesions may be treated with partial penectomy. Hyperbaric oxygen therapy (HBO) has a well-defined role in the treatment of late radiation toxicities. We present experience with HBO for medically refractory soft tissue necrosis after penile brachytherapy.

Methods and Materials

From November 2001 to January 2009, 7 men of 43 treated with penile brachytherapy for squamous carcinoma developed refractory soft tissue necrosis and were treated with HBO. All had received a prescribed dose of 60 Gy through interstitial brachytherapy using Paris system guidelines. All had failed conservative medical therapies for soft tissue necrosis.

Results

Median age was 55 years (range, 35-72 years). Comorbidities potentially effecting wound healing included hypertension (2), current smokers (5), former smoker (1) but no diabetes mellitus, or peripheral vascular disease. Median time between completion of brachytherapy and appearance of soft tissue necrosis was 13 months (range, 9-24 months) and the median interval before starting HBO was 7.5 months (range, 3-13 months). The median number of “dives” per HBO course was 40 (30-53). All 7 experienced an excellent response with healing of the necrosis and resolution of symptoms, although 3 required an additional course, 2 for consolidation of healing, and 1 for a relapse 4 months later. No patient was submitted to penectomy.

Conclusions

HBO should be considered as a treatment option in patients with refractory soft tissue necrosis of the penis after brachytherapy.     

三维适形放疗食管癌所致放射性肺炎相关因素分析

目的分析三维适形放疗食管癌患者的临床物理参数，为进一步优化食管癌适形放疗计划，减少放射性肺炎的发生提供参考标准。方法回顾性总结55例食管癌患者的三维适形治疗计划及临床资料，并对相关因素进行单因素、多因素的统计分析。结果55例中发生放射性肺炎12例，其中2级9例，3级3例。与放射性肺炎相关的因素有二程放疗、总剂量、后半程射野数、总射野数、肺V10、肺V15、肺V20、肺V25、肺D平均、食管GTVV50。Logistic多元回归分析显示二程放疗、后半程射野数、肺V25为放射性肺炎发生的独立影响因素。结论食管癌二程放疗、后半程射野数、肺V25系影响放射性肺炎发生的主要因素。     

Applicator visualization using ultrashort echo time MRI for high-dose-rate endorectal brachytherapy

PurposeThe individual channels in an endorectal applicator for high-dose-rate endorectal brachytherapy are not visible on standard MRI sequences. The aim of this study was to test whether an ultrashort echo time (UTE) MRI sequence could be used to visualize the individual channels to enable MR-only treatment planning for rectal cancer.Methods and MaterialsWe used a radial three-dimensional (3D) UTE pulse sequence and acquired images of phantoms and two patients with rectal cancer. We rigidly registered a UTE image and CT scan of an applicator phantom, based on the outline of the applicator. One observer compared channel positions on the UTE image and CT scan in five slices spaced 25 mm apart. To quantify geometric distortions, we scanned a commercial 3D geometric quality assurance phantom and calculated the difference between detected marker positions on the UTE image and corresponding marker positions on two 3D T₁-weighted images with opposing readout directions.ResultsOn the UTE images, there is sufficient contrast to discern the individual channels. The difference in channel positions on the UTE image compared with the CT was on average −0.1 ± 0.1 mm (left-right) and 0.1 ± 0.3 mm (anteroposterior). After rigid registration to the 3D T₁-weighted sequences, the residual 95th percentile of the geometric distortion inside a 550-mm-diameter sphere was 1.0 mm (left-right), 0.9 mm (anteroposterior), and 0.9 mm (craniocaudal).ConclusionsWith a UTE sequence, the endorectal applicator and individual channels can be adequately visualized in both phantom and patients. The geometrical fidelity is within an acceptable range.     

Endobronchial brachytherapy and optimization of local disease control in medically inoperable non-small cell lung carcinoma: a matched-pair analysis

PURPOSE: External beam radiation therapy (EBRT) alone for early stage, medically inoperable non-small cell lung cancer (MILC) can produce local disease control and sometimes cure. We have previously reported that higher EBRT doses result in improved disease control and, for patients with tumors > or =3.0 cm, improved survival. This report describes the impact of dose escalation with endobronchial brachytherapy boost during or following EBRT upon local disease control. METHODS AND MATERIALS: Medical records of 404 patients with MILC treated with radiotherapy alone were reviewed. Thirty-nine patients received a planned endobronchial brachytherapy boost during or following a course of EBRT. A matched-pair analysis of disease control and survival was performed by matching each brachytherapy patient to 2 EBRT patients from a reference group of the remaining patients. RESULTS: Endobronchial brachytherapy boost significantly improved local disease control over EBRT alone (58% vs. 32% at 5 years). The local control benefit for brachytherapy was found to be limited to patients with T(1-2) disease or tumors < or =5.0 cm. Among these patients treated with endobronchial boost, EBRT doses of > or =6500 cGy were necessary to optimize local disease control. No overall survival differences were observed at 3 years. Excess toxicity with brachytherapy was not observed. CONCLUSION: Endobronchial brachytherapy boost enhances local disease control rates in MILC treated with EBRT. Local control outcome is optimized when radical EBRT doses are used in conjunction with brachytherapy.     

Adjuvant electronic brachytherapy for endometrial carcinoma: A 4-year outcomes report

PurposeThe purpose of the study was to report the outcomes of a single-center adjuvant electronic brachytherapy (e-BT) experience for patients with endometrial carcinoma.Methods and MaterialsPatients were retrospectively assessed. Intracavitary e-BT was applied through a cylindrical applicator (diameters 2.5–3.5 cm). e-BT single doses ranged between 4 and 7 Gy (EQD2 ∼ 6–12, α/β of 10 Gy and an relative biological effectiveness of 1.3) at 5-mm depth. Adverse events are reported at first week, 1–3 months, 3–12 months, 12–24 months, and >24 months. The overall survival, disease-free survival, distant disease control rate, and local control rate were estimated using the Kaplan–Meier method.ResultsTwenty-nine patients were assessed. The median age was 68 [48–86] years. External beam radiotherapy was added in n = 8 (27.6%) patients. Staging was 13.8% for T1a, 51.7% for T1b, 24.1% for T2, 6.9% for T3a, and 3.4% for T3b. Grading was G3 in 51.7% (n = 15), G2 in 20.7% (n = 6), and G1 in 27.6% (n = 8). Median followup was 47 months [5–88]. Overall Grade 1, 2, and 3 toxicity was 89.7% (n = 26), 17.2% (n = 5), and 6.9% (n = 2), respectively. No Grade 3 cystitis or proctitis or any Grade 4 or 5 toxicity occurred during followup. No local recurrences were detected. Estimated distant disease control rate was 92.1% (n = 2, distant metastasis at 7 and 11 months). Estimated 4-year overall survival was 84.8% (n = 4 events, two unrelated to disease) and disease-free survival was 84.6%.ConclusionsOur data suggest that e-BT resembles a very-low-toxicity profile and a high local control rate in the adjuvant scenario for patients with endometrial carcinoma.     

Changes in insurance coverage for cancer patients receiving brachytherapy before and after enactment of the Affordable Care Act

Purpose

The Patient Protection and Affordable Care Act called for expansion of Medicaid in 2014. As some states elected to expand Medicaid and others did not, the goal of this study was to determine the effect of Medicaid expansion on the insurance status at cancer diagnosis of brachytherapy patients.