Endoluminal high-dose-rate brachytherapy for early stage and recurrent esophageal cancer in medically inoperable patients

PurposeThe management of superficial primary and recurrent esophageal cancer (EC) in medically inoperable patients is complex. Endoluminal high-dose-rate (HDR) brachytherapy has shown mixed results in terms of toxicity and local control. In this study, we examined the outcomes and toxicities in a set of patients with superficial primary and recurrent EC treated with a consistent HDR technique.Methods and MaterialsBetween 8/2008 and 7/2011, 14 patients were treated with HDR intraluminal brachytherapy, 10 (71.4%) with recurrent disease, and 4 (28.6%) with previously unirradiated lesions. Patients received three weekly fractions to a median dose of 12 Gy (range, 10–15 Gy); dose was prescribed to 7-mm median depth with mucosal dose limited to 8–10 Gy using a 12–14-mm applicator.ResultsMedian followup was 15.4 months. Overall freedom from failure (OFFF) and overall survival (OS) at 18 months were 30.8% (95% confidence interval [CI]: 5.2, 56.4) and 72.7% (95% CI: 45.3, 100), respectively. For patients with recurrent disease, OFFF and OS at 18 months were 11.1% (95% CI: 0, 32.1) and 55.6% (95% CI: 15.4, 95.8), respectively. For patients with previously unirradiated disease, OFFF and OS at 18 months were 75.0% (95% CI: 31.6, 100) and 100.0%, respectively. Eight (57.1%) patients had Grade 1 acute adverse effects; 6 (42.9%) patients had chronic Grade 1 adverse effects; 1 (7.1%) patient developed Grade 2 stricture. Grade 3 tracheoesophageal fistula occurred in 1 (7.1%) patient. One patient died before completion of treatment of unrelated causes.ConclusionsHDR endoluminal brachytherapy is a well-tolerated treatment for superficial primary and recurrent EC in medically inoperable patients.     

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.     

Radical radiotherapy with high-dose-rate brachytherapy for uterine cervix cancer long-term results

The aim of this is to report the results of radical radiotherapy in carcinoma of the cervix treated by high-dose rate (HDR) intracavitary brachytherapy and external beam radiotherapy (XRT) at a single centre in Singapore. This is a retrospective analysis of 106 consecutive cases with histologically proven cervical cancer, treated by HDR brachytherapy and XRT at the Mount Elizabeth Hospital from 1990 to 1993. External beam radiotherapy to the pelvis was delivered with 6 MV photons, to 45-50.4 Gy in 1.8 Gy fractions. High-dose-rate brachytherapy comprised two to three applications of an intrauterine tandem with paired ovoids, to a median dose of 18 Gy to point 'A', carried out during XRT. All 106 patients completed treatment. Their ages ranged from 32 to 80 years (median 57 years). Most patients presented with stage II or III disease (44 and 37%, respectively) and with squamous cell carcinoma (91%). Median follow-up time was 59 months (range 2-169 months). The 5-year relapse-free survival rate across all stages was 71%. The corresponding overall survival rate was 69%. Local control was achieved in 86 patients (81%); six patients had residual disease (6%), and 14 patients had local recurrence (13%). Fourteen patients developed metastatic disease (13%). On univariate analysis, tumour stage, haemoglobin level, number of brachytherapy treatments and overall treatment time were found to be prognostic factors for overall survival. Late complications were mild (Radiation Therapy Oncology Group score 1-2), except for one patient with grade 4 rectal toxicity. The complication rates were 8, 14 and 45%, respectively, for the rectum, bladder and vagina (stenosis). The use of two to three fractions of HDR intracavitary brachytherapy in addition to pelvic XRT achieves good outcomes.     

Image-based three-dimensional conformal brachytherapy for medically inoperable endometrial carcinoma

PurposeDefinitive radiotherapy is a viable option for medically inoperable patients with early stage endometrial cancer. We present our experience using image-based brachytherapy (BT).Methods and MaterialsPatients with medically inoperable clinical Stage I endometrial adenocarcinoma received definitive BT with or without external beam radiotherapy. High-dose-rate BT was delivered using MRI- or CT-based planning for each fraction. For patients with an MRI, gross tumor volume (GTV) was contoured although dose was still prescribed to the clinical treatment volume (CTV), including the entire uterus, cervix, and upper 1–2 cm of vagina. Equivalent 2 Gy doses (EQD₂) were calculated.ResultsThirty-eight patients were treated from 2007 to 2013, 20 receiving BT alone with a median dose of 37.5 Gy in five to six fractions. For combined therapy, median external beam and BT doses were 45 and 25 Gy in four to five fractions. With 15-month median followup, the 2-year actuarial local control and overall survival were 90.6% and 94.4%. No Grade 2–5 late toxicities were observed. Mean CTV D₉₀ EQD₂ for BT alone and combined therapy was 48.6 ± 5.6 and 72.4 ± 6.0 Gy, whereas mean GTV D₉₀ EQD₂ was 172.3 ± 59.6 and 138.0 ± 64.6 Gy.ConclusionsImage-based BT is feasible for medically inoperable early stage endometrial cancer with excellent early results. Despite low CTV doses, high doses delivered to GTV with BT likely accounts for high local control. Endometrial cancer guidelines for image-based planning are needed to define target volumes based on risk with differential dose delivery.     

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.     

Three-dimensional image-based high-dose-rate interstitial brachytherapy for vaginal cancer

PurposeTo evaluate dosimetric and clinical outcomes of three-dimensional (3D) image–based high-dose-rate (HDR) interstitial brachytherapy (HDRB) in patients with vaginal cancers.Methods and MaterialsThirty patients with vaginal cancers were treated with HDRB using Syed-Neblett template. CT scan was done after placement of needles for confirmation of placement and treatment planning. The target volume and organs at risk, including clinical target volume (CTV), rectum, bladder, and sigmoid colon, were contoured on CT scans. Twenty-eight (93.3%) patients received external beam radiation therapy at a median 45 (24.0–50.4) Gy in 12–28 fractions, followed by HDRB at 3.75–5.0 Gy per fraction in five fractions. Total doses for CTV and organs at risk from external beam radiation therapy and HDRB were summated and normalized to a biologically equivalent dose of 2 Gy per fraction.ResultsSeventeen patients (56.7%) with primary vaginal cancer and 13 patients (43.3%) with recurrent vaginal cancers were treated with 3D HDRB. The mean CTV was 39.3 ± 25.7 cm³, and the median tumor diameter was 3.3 (1.3–8.0) cm. The median biologically equivalent dose of 2 Gy per fraction for 2 cc of bladder, rectum, and sigmoid was 55.0, 56.3, 50.0 Gy, respectively. The median D₉₀ for high-risk CTV was 74.3 (36.3–81.1) Gy. The mean volume receiving 100%, 150%, and 200% of prescribed dose was 90.7 ± 10.0%, 41.3 ± 14.6%, and 17.7 ± 8.3%, respectively. With a median followup of 16.7 months, the respective 1-/2-year locoregional and overall survival rates were 84.4%/78.8% and 82.1%/70.2%, respectively. There were no Grade ≥3 gastrointestinal complications. Late complications of Grade 3 vaginal ulceration and Grade 4 vaginal necrosis were seen in two cases.ConclusionsInitial results of 3D HDRB using our fractionation schedule in the treatment of vaginal cancers showed good local response with acceptable morbidities.     

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.     

Reirradiation using high-dose-rate brachytherapy in recurrent carcinoma of uterine cervix

PurposeTo assess the feasibility of reirradiation with image-based high-dose-rate brachytherapy in previously irradiated patients with recurrent carcinoma of uterine cervix.Methods and MaterialsThirty previously irradiated patients diagnosed with central recurrence were treated with reirradiation. Martinez Universal Perineal Implant Template was used in 24 patients and Vienna applicator in 6 patients. Median interval between two radiation schedules was 25 months. Median delivered dose was 42 Gy equivalent dose at 2 Gy (EQD2; interquartile range, 37–46 Gy EQD2).ResultsAll 30 patients tolerated reirradiation well. Complete response was seen in 23 (76%) patients. With a median followup of 25 months, 2-year local control, disease-free survival, and overall survival were 44%, 42%, and 52%, respectively. Fifteen patients developed local recurrences; Local control rate was significantly higher with doses >40 Gy EQD2 (52% vs. 34%; p = 0.05). Disease-free survival was better for patients with longer interval (>25 months) between two radiotherapy schedules. Grade III radiation proctitis and cystitis was seen in 3 patients each, and Grade II small bowel toxicity was seen in 3 patients.ConclusionsReirradiation using high-dose-rate brachytherapy is feasible with acceptable outcomes in isolated local recurrence deemed unsuitable for surgery. The outcome is better with higher doses.     

Dosimetry of anal radiation in high-dose-rate brachytherapy for prostate cancer

PURPOSE: The objective of this study is to determine the radiation dose to the anus during brachytherapy using high-dose-rate Ir-192 sources. METHODS AND MATERIALS: Thermoluminescence dosimeters were used for measuring the dose to the distal part of the anus in 10 patients, and in a prostate phantom to measure the radiation dose during the transport of the radiation source. RESULTS: The measured dose to the anus in vivo was on average 0.85 Gy (range, 0.48-1.37 Gy) per treatment. The transport dose using 15 and 19 needles in the prostate phantom was 0.07 and 0.08 Gy, respectively. CONCLUSIONS: The dose delivered to the anus using high-dose-rate brachytherapy with Ir-192 sources is quite low. There is a contribution to the anal radiation dose during the transport of the Ir-192 source into the needles. However, in clinical practice when using 15-20 needles, the dose from transporting the Ir-192 source can be ignored.     

Endoluminal high-dose-rate brachytherapy for locally recurrent or persistent esophageal cancer

PurposeManagement of locally recurrent or persistent esophageal cancer (EC) after standard chemoradiation is challenging. This study updates our experience of treating medically inoperable EC patients with endoluminal high-dose-rate brachytherapy (EHDRBT) including the patients treated with a novel multiballoon channel centering esophageal applicator.Methods and MaterialsThirty-three consecutive patients with early-stage primary (n = 7), posttreatment persistent (n = 7), and recurrent (n = 19) EC treated with EHDRBT at our institution were included. Median dose and treatment lengths were 14 Gy (range 10–17.5 Gy) and 6 cm (3.5–9.0 cm), respectively. Endoscopy and biopsy were performed 3 months after EHDRBT and then every 3–6 months thereafter.ResultsMedian followup was 17.4 months (range 5.0–88.3). Grade 1 and 2 toxicities were observed in 13 (44.8%) and 11 (37.9%) patients, respectively. Grade 3 toxicity (tracheoesophageal fistula) was observed in 1 patient who had previously received two courses of external beam radiotherapy as well as a stent insertion. Median overall survival (OS) for entire cohort was 20.9 months, and 1-year OS was 78%. Complete response was achieved in 58.6% of patients with median time to failure and 1-year disease-free survival of 10.3 months (range 5.4–28.2) and 27%, respectively.ConclusionsFor medically inoperable patients with early-stage primary or local posttreatment residual or recurrent EC, EHDRBT is a well-tolerated treatment option with minimal Grade ≥3 toxicity. Brachytherapy in our hands continues to be a safe treatment option. Although 58.6% of patients achieved a complete response and the OS of this cohort is relatively good, long-term local control and cure remains a challenge.     

Needle applicator displacement during high-dose-rate interstitial brachytherapy for prostate cancer

PurposeTo introduce an effective ambulatory technique in high-dose-rate interstitial brachytherapy (HDR-ISBT) for prostate cancer, we investigated the displacement distance using our novel calculation method.Methods and MaterialsSixty-four patients treated with HDR-ISBT as monotherapy were examined. Of these, 4, 17, and 43 patients were administered treatment doses of 38 Gy (3 days), 49 Gy (4 days), and 54 Gy (5 days), respectively. For dose administration, we used 776 flexible applicators with a removable template (ambulatory technique).Using CT images, we calculated the relative coordinates of the metal markers and applicators. From these coordinates, to analyze displacement during treatment, we measured the distance between the tip of the needle applicator and the center of gravity of the markers along the average applicator vector.ResultsThe median displacement distance for all applicators was 7 mm (range, ?14 to 24), and that of each treatment schedule was 4, 6, and 9 mm for 38, 49, and 54 Gy, respectively. Of the 776 applicators, displacement of >10 mm was seen in 198 (26%) applicators and >15 mm in 57 (7%) applicators.Body height (p < 0.0001) and anticoagulant usage (p < 0.0001) were significant factors influencing displacement.ConclusionsWe investigated needle applicator displacement using our unique method. Additional cranial margins are necessary if there is no repositioning of the dwell position. CT scanning should be performed daily during treatment for checking the position of the applicator to detect and rectify the issue of displacement.     

Workflow and efficiency in MRI-based high-dose-rate brachytherapy for cervical cancer in a high-volume brachytherapy center

PurposeWe report the clinical workflow and time required for MRI-based image-guided brachytherapy (MR-IGBT) of cervical cancer patients in a high-volume brachytherapy center with 10 years of experiences to provide a practical guideline for implementing MR-IGBT into clinical use.Methods and MaterialsWe recorded the time and workflow of each procedure step within the 40 consecutive ring and tandem applicator fractions of MR-IGBT by our multidisciplinary team. We divided the entire procedure into four sections based on where the procedure was performed: (1) applicator insertion under sedation, (2) MR imaging, (3) planning, and (4) treatment delivery. In addition, we compared the current procedure time to the initial procedure time when first implementing MR-IGBT in 2007–2008 via a retrospective review.ResultsMean total procedure time was 149.3 min (SD 17.9, ranges 112–178). The multidisciplinary team included an anesthesia team, radiologist, radiation oncologist, nurses, radiation therapists, MRI technicians, dosimetrists, and physicists. The mean procedure time and ranges for each section (min) were as follows: (1) 56.2 (28.0–103.0), (2) 31.0 (19.0–70.0), (3) 44.3 (21.0–104.0), and (4) 17.8 (9.0–34.0). Under current setting, the combined mean procedure time for MR imaging and planning was 63.2 min. In comparison, the same procedure took 137.7 min in 2007–2008 period, which was significantly longer than the current workflow (p < 0.001).ConclusionsA skilled and dedicated multidisciplinary team is required for an efficient clinical workflow and delivery of MR-IGBT. Over the years, we have improved efficiency with clinical experience and continuous efforts in staff education.     

Urethral dosimetry and toxicity with high-dose-rate interstitial brachytherapy for vaginal cancer

PurposeThe tolerance and complication rates of the urethra are unknown for the interstitial high-dose-rate brachytherapy (HDR-BT) for vaginal cancer.Methods and MaterialsPatients with vaginal cancer near/involving the urethra who were treated with HDR-BT between 2008 and 2011 were included. Patients received mean external beam dose of 48.0 Gy followed by mean HDR-BT dose of 4.5 Gy/fraction for five fractions. With CT-based planning, the urethra was contoured from the bladder neck to the meatus. Doses were converted to the biologically equivalent dose in 2 Gy/fraction (EQD₂).ResultsA total of 16 patients were included, and the EQD₂ D₉₀ was 74.9 Gy. The urethral volume was 1.31 cm³, and the EQD₂ to 0.1 and 1 cm³ were 76.2 and 48.9 Gy, respectively. Two of the 6 patients with urethral involvement developed urethral necrosis. The D₉₀ for these 2 patients was 76.8 Gy, and the urethral doses to 0.1 and 1 cm³ were 95.1 and 45.8, respectively. Those who developed severe urethral toxicity had a trend to urethral EQD₂ (95.1 Gy vs. 73.4 Gy, p = 0.1) and significantly higher dose per fraction of HDR-BT to 0.1 cm³ of the urethra (5.7 Gy vs. 3.7 Gy, p = 0.02) when compared with those who did not develop severe urethral toxicity.ConclusionsThis study is among the first to assess urethral dosimetry for patients treated with HDR-BT for vaginal cancer. Patients who received five fractions of higher than 5 Gy/fraction to 0.1 cm³ of urethra (estimated EQD₂ of 85 Gy) are at increased risk of severe urethral toxicity.     

Definitive radiation therapy for endometrial cancer in medically inoperable elderly patients

PurposeWith the increasing elderly population, more women with newly diagnosed endometrial cancer may not be surgical candidates due to medical comorbidities. Definitive radiation therapy with external beam radiation (EBRT) and/or brachytherapy is a reasonable primary treatment for endometrial cancer in patients who cannot undergo surgery.MethodsA retrospective review identified 26 women 75 years and older with endometrial cancer who were not operative candidates due to comorbidities and received definitive radiation.ResultsThe median age of the treated patients was 83, all of whom had significant medical comorbidities precluding surgical treatment. Seventy-three percent of the patients had stage T1 disease, 19% were stage T2, and 8% were stage T3. Seventy-three percent of patients received EBRT before brachytherapy (median dose: 45 Gy). The median brachytherapy dose was 20 Gy in 5 fractions. The types of brachytherapy used were Rotte Y applicator (42%), tandem and cylinder (42%), and ring and tandem (16%). Median followup was 12 months (1–60 months). No treatment breaks were required for the entire group and only 2 patients (8%) developed late toxicity. The overall survival for all patients was 89% and 28% at 1 and 2 years, respectively. Disease-specific survival for all patients was 93% at 1 year and 73% at 3 years.ConclusionsThe results in this study indicate that definitive radiation with EBRT and/or brachytherapy for endometrial cancer is feasible and well tolerated in an elderly population.