Inverse-planned gynecologic high-dose-rate interstitial brachytherapy: clinical outcomes and dose--volume histogram analysis

PurposeTo present clinical outcomes and dose–volume histogram parameters of three-dimensional image–based high-dose-rate interstitial brachytherapy (HDR-ISBT) in patients with primary or recurrent gynecologic cancer unsuitable for intracavitary brachytherapy (ICB).Methods and MaterialsRecords of 43 women treated between 2001 and 2009 with iridium-192 gynecologic HDR-ISBT boost, using a Syed–Neblett template and inverse planning simulated annealing dose optimization, were reviewed. Median HDR-ISBT dose was 30 Gy, delivered in 4–6 Gy/fraction. Dose–volume histogram parameters recommended by the Groupe Européen de Curiethérapie–European Society for Therapeutic Radiology and Oncology for image-based ICB were analyzed. Total doses were normalized to 2 Gy fractions (biologically equivalent dose in 2 Gy fractions). Local control (LC) and survival were calculated using Kaplan–Meier method. Toxicities were defined according to Common Terminology Criteria for Adverse Events v3.0.ResultsThere were 34 primary malignancies (cervix = 12, vagina = 15, Bartholin’s gland = 5, and vulva = 2) and 9 recurrences. International Federation of Gynecology and Obstetrics stage distribution for primary cancers was I = 2, II = 13, III = 15, and IV = 4. Median followup was 19.3 months (range, 0–92.2). Two-year LC was 87% for primary cancers, and 45% for recurrent cancers, respectively (p = 0.0175). Median V₁₀₀, D₉₀, and D₁₀₀ for clinical target volume were 97.6%, 90.2, and 68.7 Gy₁₀, respectively. Median bladder and rectal D_2 cc were 76.6 and 79.5 Gy₃, respectively. Median urethral D₁₀ was 80.6 Gy₃. Twelve patients experienced Grades 3 and 4 late morbidity, but toxicities were transient. Only 2 patients had persistent severe toxicities. A trend toward increased risk for vaginal necrosis was observed with a clinical target volume >84 cc.ConclusionsHDR-ISBT may achieve good LC in gynecologic cancer unsuitable for ICB, especially in primary malignancies with a 2-year LC rate higher than 85%. Delivery of such high doses has potential advantages but may predispose to adverse effects, reversible in most cases.     

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.     

Phase II trial of image-based high-dose-rate interstitial brachytherapy for previously irradiated gynecologic cancer

PurposeTo report the disease-free Grade ≥3 complication-free survival of a Phase II protocol of reirradiation with high-dose-rate (HDR) interstitial brachytherapy (ITB) in previously irradiated gynecologic cancer.Methods and MaterialsFifteen patients with previously irradiated cervical (n = 6), endometrial (n = 6), and vulvovaginal tumors (n = 3) were treated with HDR-ITB alone to a median dose of 38 Gy in 8 b.i.d. fractions over 4 consecutive days. Prior treatments included surgery (n = 12; 80%), external irradiation (n = 15; 100%), and brachytherapy (n = 9; 60%). Average clinical target volume Size was 60.9 cc (range, 14.8–165.3 cc), and median time to reirradiation was 3.9 years (range, 0.4–22.7 years).ResultsWith a median followup of 2.8 years (range, 1.2–9.2 years), 3 patients (20.0%) developed Grade ≥3 toxicity consisting of Grade 3 intestinal obstruction (n = 1), Grade 4 rectovesical fistula (n = 1), and Grade 5 intestinal obstruction (n = 1). Six patients remain alive and without evidence of disease at last followup. Two patients are alive with disease progression, and 7 patients have died, 4 of them from disease progression and 3 from other causes. The 2-year disease-free Grade ≥3 complication-free survival was 40%.ConclusionsHDR-ITB alone is a reasonable salvage treatment option in a significant number of patients with previously irradiated gynecologic tumors.     

Inter-fractional variation of markers and applicators in single-implant high-dose-rate interstitial brachytherapy for gynecologic malignancies

PURPOSEImplanted fiducial markers are a commonly used tool in delineating the CTV in high-dose-rate interstitial brachytherapy (HDR-ISBT) for gynecologic malignancy, but their reliability in gynacological sites is not well understood. These markers and interstitial applicators can experience interfractional motion due to organ swelling or other anatomical changes. The purpose of this study was to evaluate the spatial variation of these features.METHODS AND MATERIALSThe spatial positions of 50 implanted markers and 202 needles were tracked in 15 patients treated over 70 fractions of HDR brachytherapy. Marker and/or needle coordinates were extracted from CT images with contours and dose distributions. Automated analysis determined marker self-consistency and displacements between various elements of the implant.RESULTSFrom start to end fraction, the relative positions of the markers experienced an average magnitude displacement of 4.5 ± 3.0 mm while the average displacement of the applicator tips was 11 ± 8 mm, relative to their respective centers of mass (CM).CONCLUSIONSMarkers implanted lateral and superior to the CTV experience greater drift than other implant locations.     

High-dose-rate interstitial brachytherapy for gynecologic malignancies

PURPOSE: The study aimed to assess the outcome of locally advanced cervical and vaginal cancer treated with high-dose-rate interstitial brachytherapy (HDRB). METHODS AND MATERIALS: Between 1998 and 2004, 16 previously unirradiated patients with locally advanced cervical and vaginal cancer not suitable for intracavitary brachytherapy because of distorted anatomy or extensive vaginal disease were treated with HDRB in combination with external beam radiotherapy. All patients received whole pelvis external beam radiation therapy (EBRT) followed by interstitial implantation. The median whole pelvis external beam dose was 45 Gy (range, 39.6-50.4 Gy) with 11 patients receiving parametrial boost to a median dose of 9 Gy. Twelve (75%) of these patients received chemotherapy concurrent with external beam. All patients received a single HDRB procedure using a modified Syed-Neblett template. A CT scan was performed postimplant for needle placement verification and treatment planning purpose. Dose was prescribed to the tumor volume based on the radiographic and clinical examination. All patients received 18.75 Gy in five fractions delivered twice daily. The median followup was 25 months (6-69 months). RESULTS: Median cumulative biologic effective dose (EBRT+HDRB) to tumor volume was 78.9 Gy10 with the range of 72.5-85.2Gy10. Median cumulative biologic effective dose for the rectum and bladder were 99.4 Gy3 (range, 79.6-107.8 Gy3) and 96.4 Gy3 (range, 78.3-105.3 Gy3), respectively. Complete response was achieved in 13 (81%) patients with 3 patients having persistent disease. Five of these 13 patients developed recurrence at a median time of 14 months (distant in 4 and local and distant in 1). The 5-year actuarial local control and cause-specific survival were 75% and 64%, respectively. In subset analysis, 5-year actuarial local control was 63% for cervical cancer patients and 100% for vaginal cancer patients. No patient had acute Grade 3 or 4 morbidity. Grade 3 or 4 delayed morbidity resulting from treatment occurred in 1 patient with 5-year actuarial rate of 7%. Three patients had late Grade 2 rectal morbidity and 1 patient had Grade 2 small bowel morbidity. CONCLUSIONS: Our series suggests that single interstitial implantation procedure with five fractions of 3.75 Gy each to target volume is an effective and safe fractionation schedule. The integration of imaging modality helps in decreasing dose to the critical organs. Additional patients and followup are ongoing to determine the long-term efficacy of this approach.     

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.     

Online correction of catheter movement using CT in high-dose-rate prostate brachytherapy

PurposeTo present a clinical procedure that readjusts catheters to its planned positions based on pretreatment computed tomography (CT) for patients undergoing high-dose-rate (HDR) prostate brachytherapy, and evaluate the magnitude and dosimetric impact of the adjustments.Methods and MaterialsPatients received a pretreatment verification CT (vCT) before each fraction. The vCT dataset was imported to the treatment-planning system and fused to the planning CT (pCT) by rigid-body registration based on the implanted fiducials within the prostate. Catheter positions in the vCT were then compared with catheter positions in the pCT in a reconstructed plane through each catheter. Any catheter with difference in penetration larger than 3 mm was manually adjusted by a radiation oncologist before treatment. To evaluate treatment quality, the patient's plan was applied to the vCT off-line and dose delivered to prostate and normal structures were compared with their planned value.ResultsForty-four fractions of 13 consecutive patients were treated using this method. Thirty-nine fractions had at least one catheter adjusted before treatment. A total of 651 catheters were assessed, and 194 catheters (30%) were adjusted by an average amount of 5.8 ± 1.9 mm. In eight fractions the prostate D₉₀ would have decreased by more than 10% from the planned value (with a maximum of 32%) if the catheter displacements were not rectified. After the adjustment, the maximum deviation of D₉₀ was 10.6%. The improvement in D₉₀ is 24% per 1 cm of time-averaged adjustment.ConclusionsInterfraction catheter motion occurs without any particular pattern. Using pretreatment CTs and restoring each catheter to its planned position ensures that the delivered treatment closely matches the treatment plan and therefore enhances the overall quality of the HDR treatment. The procedure can be readily implemented in any clinical setting.     

Radioablation of adrenal gland malignomas with interstitial high-dose-rate brachytherapy

Purpose

To assess the efficacy, safety, and outcome of image-guided high-dose-rate (HDR) brachytherapy in patients with adrenal gland metastases (AGM).

Materials and methods

From January 2007 to April 2014, 37 patients (7 female, 30 male; mean age 66.8 years, range 41.5–82.5 years) with AGM from different primary tumors were treated with CT-guided HDR interstitial brachytherapy (iBT). Primary endpoint was local tumor control (LTC). Secondary endpoints were time to untreatable progression (TTUP), time to progression (TTP), overall survival (OS), and safety. In a secondary analysis, risk factors with an influence on survival were identified.

Results

The median biological equivalent dose (BED) was 37.4?Gy. Mean LTC after 12 months was 88%; after 24 months this was 74%. According to CTCAE criteria, one grade 3 adverse event occurred. Median OS after first diagnosis of AGM was 18.3 months. Median OS, TTUP, and TTP after iBT treatment were 11.4, 6.6, and 3.5 months, respectively. Uni- and multivariate Cox regression analyses revealed significant influences of synchronous disease, tumor diameter, and the total number of lesions on OS or TTUP or both.

Conclusion

Image-guided HDR-iBT is safe and effective. Treatment- and primary tumor-independent features influenced survival of patients with AGM after HDR-iBR treatment.

     

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.     

A surrogate urethra for real-time planning of high-dose-rate prostate brachytherapy

PurposeThis study characterizes prostatic urethra cross-section to develop a surrogate urethra for accurate prediction of urethral dose during real-time high-dose-rate prostate brachytherapy.Materials and MethodsArchived preoperative transrectal ultrasound images from 100 patients receiving low-dose-rate prostate brachytherapy were used to characterize the prostatic urethra, contoured on ultrasound using aerated gel. Consensus contours, defined using majority vote, described commonalities in cross-sectional shape across patients. Potential simplified surrogates were defined and evaluated against the true urethra. The best performing surrogate, a circle of varying size (CS) was retrospectively contoured on 85 high-dose-rate prostate brachytherapy treatment plans. Dose to this recommended surrogate was compared with urethral doses estimated by the standard 6 mm circle surrogate.ResultsClear variation in urethral cross-sectional shape was observed along its length and between patients. The standard circle surrogate had low predictive sensitivity (61.1%) compared with true urethra because of underrepresentation of the verumontanum midgland. The CS best represented the true urethra across all validation metrics (dice: 0.73, precision: 67.0%, sensitivity: 83.2%, conformity: 0.78). Retrospective evaluation of planned doses using the CS surrogate resulted in significant differences in all reported urethral dose parameters compared with the standard circle, with the exception of D_100%. The urethral dose limit (115%) was exceeded in 40% of patients for the CS surrogate.ConclusionsThe proposed CS surrogate, consisting of circles of varying diameter, is simple yet better represents the true urethra compared with the standard 6 mm circle. Higher urethral doses were predicted using CS, and the improved accuracy of CS may offer increased predictive power for urethral toxicity, a subject of future work.     

Long-term results of multicatheter interstitial high-dose-rate brachytherapy for accelerated partial-breast irradiation

Purpose

The purpose of this study was to report the long-term results of women treated in one center with accelerated partial-breast irradiation (APBI) with interstitial high-dose-rate (HDR) brachytherapy.

New ambulatory implant technique of high-dose-rate interstitial brachytherapy for prostate cancer

Purpose The aim of this study was to improve the performance status of prostate cancer patients during high-dose-rate interstitial brachytherapy (HDR-ISBT). To this end, we have developed a new ambulatory implant technique. Materials and methods Ten prostate cancer patients were treated with HDR-ISBT as monotherapy from October 2003 until March 2004. We utilized a new removable template, a flexible applicator with a nonmetallic bead and button stopper, and an inner catheter connecting the applicator and the transfer tube of the brachytherapy unit. We shortened the connector end of the flexible applicator to enable the patient to sit down and walk freely during the treatment time. Results All 10 patients could walk without any support. No problem in the application was observed. Conclusion Our new ambulatory implant technique for HDR-ISBT was able to improve the performance status of prostate cancer patients.     

Efficacy of high-dose-rate interstitial brachytherapy in patients with oral tongue carcinoma

PurposeTo evaluate the results of high-dose-rate (HDR)-interstitial brachytherapy (ISBT) in oral tongue carcinomas.Methods and MaterialsBetween September 1999 and August 2007, 50 patients were treated for oral tongue carcinoma with HDR-ISBT. The patient's mean age was 58 years. Forty-two patients were in T1–2 stage and 8 patients were in T3 stage; 16 patients were in N+ stage and 34 patients in N0 stage. Exclusive ISBT was given to 17 patients (34%) in T1–2 N0 stage and complementary to external beam radiotherapy (EBRT) to 33 patients (66%). A perioperative technique was performed on 14 patients. The median total dose was 44 Gy when HDR was used alone (4 Gy per fraction) and 18 Gy when complementary to 50 Gy EBRT (3 Gy per fraction).ResultsThe median followup was 44 months. Actuarial disease-free survival rates at 3 and 5 years were 81% and 74%, respectively. Local failure developed in 7 patients. Actuarial local control (LC) rates were 87% and 79% at 3 and 5 years in T1–2 stage 94.5% and 91% and T3 stage 43% and 43% (with salvage surgery). Exclusive HDR cases showed LC in 100% of the cases, and the combined group (EBRT + HDR) showed LC in 80% and 69% of the cases at 3 and 5 years (p = 0.044). Soft-tissue necrosis developed in 16% and bone necrosis in 4% of the cases.ConclusionsHDR brachytherapy is an effective method for the treatment of oral tongue carcinoma in low-risk cases. Doses per fraction between 3 and 4 Gy yield LC and complication rates similar to low-dose rate. The perioperative technique promises encouraging results.     

Outcomes of freehand interstitial brachytherapy in advanced gynecologic malignancies

PurposeThe purpose of the study is to present the first results of freehand interstitial brachytherapy (ISBT) used to treat patients with carcinoma of the cervix and the vagina.Methods and MaterialsPatients diagnosed with carcinoma of the cervix or carcinoma of the vagina who were not suitable for intracavitary brachytherapy were treated with freehand ISBT. The implant was performed transperineally using C arm or transrectal ultrasound guidance. Patients received an external beam radiotherapy dose of 50 Gy in 25 fractions. The dose delivered by high-dose-rate ISBT was 18 Gy in three fractions, 6 Gy per fraction, 6 h apart. The brachytherapy dose volume parameters were analyzed after CT-based planning using GEC ESTRO image-guided brachytherapy-based guidelines.ResultsFrom June 2018 till November 2018, 14 patients were treated with freehand ISBT. The mean dose received by 90% of the high-risk clinical target volume (D₉₀) was 82 Gy EQD2₁₀ for patients with carcinoma of the cervix and 80 Gy EQD2₁₀ for patients with carcinoma of the vagina_. The mean dose received by 2 cc volume of the bladder and rectum was 80 Gy EQD2₃ and 70 Gy EQD2₃ for patients with carcinoma of the cervix and 75 Gy EQD2₃ and 72 Gy EQD2₃ for patients with carcinoma of the vagina, respectively. The mean dose received by 2 cc of the sigmoid was 65 Gy EQD2₃ for cervical carcinoma and 58 Gy EQD2₃ for vaginal carcinoma, respectively. At a median followup of 14 months, 2 patients developed local recurrence. Two patients developed Grade 2 gastro intestinal toxicity, and 1 patient developed Grade 2 genitourinary toxicity. None of the patients developed Grade 3 or 4 toxicities.ConclusionA freehand interstitial implant is feasible in resource limited settings and provides acceptable local control with minimal acute toxicity.     

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.