A general framework to develop a radiomic fingerprint for progression-free survival in cervical cancer.

PURPOSE: Treatment of locally advanced cervical cancer patients includes chemoradiation followed by brachytherapy. Our aim is to develop a delta radiomics (DRF) model from MRI-based brachytherapy treatment and assess its association with progression free survival (PFS). MATERIALS AND METHODS: A retrospective analysis of FIGO stage IB- IV cervical cancer patients between 2012 and 2018 who were treated with definitive chemoradiation followed by MRI-based intracavitary brachytherapy was performed. Clinical factors together with 18 radiomic features extracted from different radiomics matrices were analyzed. The delta radiomic features (DRFs) were extracted from MRI on the first and last brachytherapy fractions. Support Vector Machine (SVM) models were fitted to combinations of 2-3 DRFs found significant after Spearman correlation and Wilcoxon rank sum test statistics. Additional models were tested that included clinical factors together with DRFs. RESULTS: A total of 39 patients were included in the analysis with a median patient age of 52 years. Progression occurred in 20% of patients (8/39). The significant DRFs using two DRF feature combinations was a model using auto correlation (AC) and sum variance (SV). The best performing three feature model combined mean, AC & SV. Additionally, the inclusion of FIGO stages with the 2- and 3 DRF combination model(s) improved performance compared to models with only DRFs. However, all the clinical factor + DRF models were not significantly different from one another (all AUCs were 0.77). CONCLUSIONS: Our study shows promising evidence that radiomics metrics are associated with progression free survival in cervical cancer.

Dosimetric predictors of local control and complications in gynecologic transperineal implant patients: The medical college of wisconsin experience.

PURPOSE: Investigate the relationship between dosimetric parameters with local control (LC) and complications following transperineal high-dose rate (HDR) interstitial brachytherapy (ISBT) for gynecologic (GYN) malignancies. METHODS AND MATERIALS: Between 2001 and 2016, 59 patients were treated for primary or recurrent GYN malignancies. Most patients received external beam irradiation, followed by transperineal ISBT via the Syed-Neblett applicator set with CT-based planning. Treatment plans were retrospectively reviewed to evaluate for an association among LC or toxicity with the equivalent dose at 2 Gy per fraction (EQD2) for the clinical target volume (CTV), 0.1 cc (D0.1cc), and 2 cc (D2cc) volumes of the organs at risk (OAR), low/high dose volumes for the OAR and CTV, and ratio of dose at the core vs. the implant periphery. RESULTS: The median follow-up among survivors was 24 months. 34% of patients had a component of local failure and in 12%, this was isolated. Late grade 3 (G3) toxicity occurred in 15% of patients. There were no G4-5 toxicities. Rectal D0.1cc > 75 Gy trended toward significance in predicting the development of non-fistula late G2-3 rectal complications. Bladder D0.1cc > 94 Gy significantly predicted for the development of late G2-3 vesicovaginal fistula formation. The ratio of the total dose at the vaginal surface to the needle periphery above 121% trended in predicting for any complication or fistula formation. CONCLUSIONS: HDR ISBT combined with EBRT achieved LC in 66% of patients with advanced or recurrent GYN cancers. Rectal and bladder D0.1cc doses may be predictive of complications as may the ratio of the implant dose at the core vs. periphery.

3-T MRI-based adaptive brachytherapy for cervix cancer: treatment technique and initial clinical outcomes.

PURPOSE: To report the techniques and initial clinical outcomes for MRI-based adaptive brachytherapy (MRIB-ABT) using 3-T MRI. METHODS AND MATERIALS: All patients who underwent MRIB-ABT between January 2008 and June 2012 for cervical cancer using 3-T MRI for at least three fractions were retrospectively reviewed. The institutional standard for initiation of brachytherapy planning was 100% of dose at point A and 160% at the vaginal surface with five fractions of 500-550 cGy at Point A. The dose distribution was modified to enhance coverage of the high-risk clinical target volume (HR-CTV) and to spare the organs at risk (OAR) by altering dose specification distances around the tandem and the percentage of the Point A dose around the ring or ovoids. RESULTS: Eighteen patients (FIGO stages IB = 4, II = 12, III = 1, and IVA = 1) underwent eighty-two 3-T MRI-based insertions. All patients received 3D conformal, external beam radiation (45-50.4 Gy). The median gross tumor volume pretreatment was 38 cm(3) (2-165 cm(3)) compared with 4.8 cm(3) (1-9 cm(3)) at the first high-dose rate fraction with a median volume reduction of 88%. Dose specification at the level of Point A was altered in 51% of 3-T MRI fractions from the standard 20 mm (range, 14-18 mm) and in 8% at the ring surface to optimally cover the HR-CTV and spare the OAR. The 2-year local control, disease-specific survival, and overall survival are 100%, 100%, and 93%, respectively. CONCLUSIONS: MRIB-ABT using 3-T MRI for treatment of cervix cancer allows for customized alterations in dose specification that minimize dose to the OAR and maximize coverage of the HR-CTV.

American Brachytherapy Society consensus guidelines for interstitial brachytherapy for vaginal cancer.

PURPOSE: To present recommendations for the use of interstitial brachytherapy in patients with vaginal cancer or recurrent endometrial cancer in the vagina. METHODS: A panel of members of the American Brachytherapy Society reviewed the literature, supplemented that with their clinical experience, and formulated recommendations for interstitial brachytherapy for primary or recurrent cancers in the vagina. RESULTS: Patients with bulky disease (approximately >0.5cm thick) should be considered for treatment with interstitial brachytherapy. The American Brachytherapy Society reports specific recommendations for techniques, target volume definition, and dose-fractionation schemes. Three-dimensional treatment planning is recommended with CT scan and/or MRI. The treatment plan should be optimized to conform to the clinical target volume and should reduce the dose to critical organs, including the rectum, bladder, urethra, and sigmoid colon. Suggested doses in combination with external beam radiation therapy and summated equivalent doses in 2Gy fractions are tabulated. CONCLUSION: Recommendations are made for interstitial brachytherapy for vaginal cancer and recurrent disease in the vagina. Practitioners and cooperative groups are encouraged to use these recommendations to formulate treatment and dose-reporting policies. Such a process will result in meaningful outcome comparisons, promote technical advances, and lead to appropriate utilization of these techniques.

American Brachytherapy Society consensus guidelines for adjuvant vaginal cuff brachytherapy after hysterectomy.

PURPOSE: To develop recommendations for the use of adjuvant vaginal cuff brachytherapy after hysterectomy and update previous American Brachytherapy Society (ABS) guidelines. METHODS AND MATERIALS: A panel of members of the ABS performed a literature review, supplemented their clinical experience, and formulated recommendations for adjuvant vaginal cuff brachytherapy. RESULTS: The ABS endorses the National Comprehensive Cancer Network guidelines for indications for radiation therapy for patients with endometrial cancer and cervical cancer and the guidelines on quality assurance of the American Association on Physicists in Medicine. The ABS made specific recommendations for applicator selection, insertion techniques, target volume definition, dose fractionation, and specifications for postoperative adjuvant vaginal cuff therapy. The ABS recommends that applicator selection should be based on patient anatomy, target volume geometry, and physician judgment. The dose prescription point should be clearly specified. Suggested doses were tabulated for treatment with brachytherapy alone, and in combination with external beam radiation therapy, when applicable. A properly fitted brachytherapy applicator should be selected that conforms to the vaginal apex and achieves mucosal contact with optimal tumor and normal tissue dosimetry. Dose prescription points may be individually selected but doses should be reported at the vaginal surface and at 0.5-cm depth. CONCLUSIONS: Recommendations are made for adjuvant vaginal cuff brachytherapy. Practitioners and cooperative groups are encouraged to use these recommendations to formulate their treatment and dose reporting policies. These recommendations will permit meaningful comparisons of reports from different institutions and lead to better and more appropriate use of vaginal brachytherapy.

Adjuvant high dose rate brachytherapy for soft tissue sarcomas: initial experience report.

PURPOSE: Adjuvant high-dose-rate brachytherapy (HDRBT) offers advantages over low dose rate brachytherapy (LDRBT), although there are little data on local tumor control and treatment related toxicity. We report outcome in patients with primary, recurrent, and metastatic extremity and superficial trunk soft tissue sarcoma. MATERIAL AND METHODS: Eleven patients (12 sites) with intermediate or high grade sarcoma were treated with adjuvant HDRBT following surgical resection. Patients were treated at 3.4 Gy fractions delivered twice daily to a total dose of 34 Gy (1 patient received 9 fractions). RESULTS: With median follow-up of 20.8 months, 1 patient developed a local recurrence. 2-year local control and overall survival are 89% and 71%, respectively. Wound complications occurred in 3 sites. Two of the wound complications developed in the area of previous external beam radiotherapy (EBRT). CONCLUSION: Surgical resection followed by HDRBT is associated with excellent early local tumor control and acceptable wound complication.

Recommendations from gynaecological (GYN) GEC ESTRO working group (II): concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy-3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, radiobiology.

The second part of the GYN GEC ESTRO working group recommendations is focused on 3D dose-volume parameters for brachytherapy of cervical carcinoma. Methods and parameters have been developed and validated from dosimetric, imaging and clinical experience from different institutions (University of Vienna, IGR Paris, University of Leuven). Cumulative dose volume histograms (DVH) are recommended for evaluation of the complex dose heterogeneity. DVH parameters for GTV, HR CTV and IR CTV are the minimum dose delivered to 90 and 100% of the respective volume: D90, D100. The volume, which is enclosed by 150 or 200% of the prescribed dose (V150, V200), is recommended for overall assessment of high dose volumes. V100 is recommended for quality assessment only within a given treatment schedule. For Organs at Risk (OAR) the minimum dose in the most irradiated tissue volume is recommended for reporting: 0.1, 1, and 2 cm3; optional 5 and 10 cm3. Underlying assumptions are: full dose of external beam therapy in the volume of interest, identical location during fractionated brachytherapy, contiguous volumes and contouring of organ walls for >2 cm3. Dose values are reported as absorbed dose and also taking into account different dose rates. The linear-quadratic radiobiological model-equivalent dose (EQD2)-is applied for brachytherapy and is also used for calculating dose from external beam therapy. This formalism allows systematic assessment within one patient, one centre and comparison between different centres with analysis of dose volume relations for GTV, CTV, and OAR. Recommendations for the transition period from traditional to 3D image-based cervix cancer brachytherapy are formulated. Supplementary data (available in the electronic version of this paper) deals with aspects of 3D imaging, radiation physics, radiation biology, dose at reference points and dimensions and volumes for the GTV and CTV (adding to [Haie-Meder C, Pötter R, Van Limbergen E et al. Recommendations from Gynaecological (GYN) GEC ESTRO Working Group (I): concepts and terms in 3D image-based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV. Radiother Oncol 2005;74:235-245]). It is expected that the therapeutic ratio including target coverage and sparing of organs at risk can be significantly improved, if radiation dose is prescribed to a 3D image-based CTV taking into account dose volume constraints for OAR. However, prospective use of these recommendations in the clinical context is warranted, to further explore and develop the potential of 3D image-based cervix cancer brachytherapy.

Patterns of brachytherapy practice for patients with carcinoma of the cervix (1996-1999): a patterns of care study.

PURPOSE/OBJECTIVE: To analyze the details of brachytherapy practice in patients treated for carcinoma of the cervix in the United States between 1996 and 1999. METHODS AND MATERIALS: Radiation facilities were selected from a stratified random sample. Patients were randomly selected from lists of eligible patients treated at each facility. A total of 442 patients' records were reviewed in 59 facilities to obtain data about patients' characteristics, evaluation, tumor extent, and treatment. National estimates were made using weights that reflected the relative contribution of each institution and of each patient within the sampled institutions. From our survey we estimate that 16,375 patients were treated in the United States during this study period. Unless otherwise specified, brachytherapy practice was based on the 408 patients who had their brachytherapy or all their treatment at the surveyed facility. RESULTS: A total of 91.5% of patients underwent brachytherapy at the initial treating institution; 8.5% were referred to a second site for brachytherapy. Forty-two percent of U.S. facilities referred at least some patients to a second facility for brachytherapy. Of U.S. facilities that treated < or =2 eligible patients per year, 61% referred all of their patients to a second facility for brachytherapy or treated with external RT alone; none of the U.S. facilities with larger experience (>2 eligible patients per year) referred all their patients to a second facility for brachytherapy treatment, but 28% referred some patients to an outside facility for brachytherapy. Overall, 94% of patients who completed treatment with curative intent received brachytherapy. Of these patients who had brachytherapy, 77.8%, 13.3%, and 0.9%, respectively, were treated with low-dose-rate (LDR), high-dose-rate (HDR), or a combination of HDR and LDR brachytherapy; 7.9% had interstitial brachytherapy (5.7% LDR and 1.9% HDR, 0.3% mixed). In facilities that treated >2 patients per year, 15.5% and 9.4% of brachytherapy procedures included HDR or interstitial, respectively; in facilities that treated fewer patients, 3.4% had HDR brachytherapy, and only 1.2% had interstitial brachytherapy. Patients treated with LDR intracavitary radiotherapy had one (23.5%), two (74.1%), or three (2.4%) implants. For patients treated with curative intent who completed radiation therapy with LDR intracavitary radiation therapy without hysterectomy, the median brachytherapy dose to Point A was 40.3 Gy, and the median total dose to Point A was 82.9 Gy. Patients were treated with HDR intracavitary radiation therapy using a variety of treatment schedules using 1-2 fractions (7.5%), 3-4 fractions (17.4%), 5-6 fractions (38.5%), 7-9 fractions (33.5%), or 12 fractions (3%). Fraction sizes were <500 cGy (29.5%), 500-<600 (25.2%), 600 (28.1%), >600 (8%), or unknown (9.2%). For patients treated with HDR, the median total dose to Point A (corrected for fraction size using a alpha/beta = 10) was 85.8 Gy (range: 56.2-116.1 Gy). At institutions treating <500 new patients per year, the percentage of patients receiving a brachytherapy dose <40 Gy was significantly higher than at institutions treating > or =500 new patients per year (p < 0.0001). For LDR intracavitary radiation therapy, 5.8% had neither bladder nor rectal doses recorded for any of their implants, whereas in HDR intracavitary radiation therapy, 73.4% had neither bladder nor rectal doses recorded for any of their implants. The median total duration of radiation therapy was identical for patients who had HDR or LDR intracavitary radiation therapy (57 days). For LDR at institutions treating <500 new patients per year, the percentage of patients with treatment duration >56 days was significantly greater than at institutions > or =500 new patients per year (p = 0.002). Of the patients who had LDR intracavitary radiation therapy implants, 65% were treated using tandem and shielded Fletcher-Suit-Delclos colpostats; other patients had mini ovoids (10.9%), cylinders (3.9%), Henschke (3.7%), or other/mixed applicators (16.5%). In contrast, of patients treated with HDR intracavitary radiation therapy, 68.7% had tandem and rings, 18.2% Fletcher-Suit-Delclos ovoids, 7.5% mini ovoids, 2.3% cylinders, and 3.2% other or mixed applicators. CONCLUSIONS: The median duration of treatment and median Point A dose were very similar for patients treated with HDR or LDR. Patients with HDR were treated using a variety of treatment schedules. Different applicator types were favored for LDR vs. HDR. Of patients treated with HDR, 73.4% had no brachytherapy bladder or rectal doses recorded, suggesting that full dosimetric calculations were performed only for the first fraction in many institutions. Facility size significantly impacted on referral to another institution for brachytherapy, brachytherapy dose, and treatment duration.

Clinical implementation of AAPM TG61 protocol for kilovoltage x-ray beam dosimetry.

Historically, there have been a variety of dosimetry protocols used for kilovoltage x-ray therapy beams with a set of conversion factors and correction factors taken from different references. Corresponding to the continued installation and use of kilovoltage machines, the American Association of Physicists in Medicine (AAPM) presented a unified protocol developed by Task Group 61 (TG61). TG61 determines the absorbed dose to water with an ionization chamber calibrated in air in terms of air kerma (Nk). TG61 presents both an in-air method and an in-phantom method. In this work we only examine the TG61 in-air method. Our traditional dosimetry procedure, which is based upon NCRP Report 69 and on material found in standard medical physics texts, has been compared to the TG61. A variety of kilovoltage beam energies were examined with a set of various field sizes and source to surface distances. TG61 published updated data for the mass absorption coefficient ratios, backscatter factors, and the average energy per ion pair factor. The following conclusions have been reached: (1) Our traditional procedures and the TG61 protocol for in-air measurements are equivalent. (2) The conversion and correction factors used in TG61 are different by up to 4.5% compared to the old factors that we have used. (3) The application of the TG61 factors can result in up to 5% differences in the determination of the absorbed dose.

CT-guided high-dose-rate dose prescription for cervical carcinoma: the importance of uterine wall thickness.

PURPOSE: To evaluate the use of CT imaging to guide dose prescription for high-dose-rate brachytherapy in cervical cancer, by defining the uterine wall thickness and the proximity of the rectosigmoid, bladder, and small bowel. METHODS AND MATERIALS: From 1994-2000, 40 patients with cervical cancer underwent treatment with external beam radiation therapy plus high-dose-rate brachytherapy. A pelvic CT scan was performed following applicator placement, and was analyzed to determine anterior and posterior uterine wall thickness, and the distance to the bladder and rectosigmoid. The dose prescription was initially at Point A, but in some patients, was altered based on the thickness of the uterine wall. RESULTS: Measurements in the region of the lower and upper uterine wall were analyzed separately. Nearly half (46%) of the patients had an average anterior or posterior wall thickness of <20 mm. A correlation was observed between thinner anterior lower uterine walls and increased late bladder and ureteral toxicity, and between thinner anterior upper uterine walls and increased late small-bowel toxicity. CONCLUSIONS: A significant number of patients have uterine walls <2 cm in thickness. The use of CT imaging can identify patients in whom the conventional dose specification point may need to be altered to maintain the therapeutic ratio.