Radiation therapy for vulvar cancer: consensus guidelines of the GINECOR working group of the Spanish Society of Radiation Oncology. Part 1: clinical recommendations

Purpose The present consensus statement was developed by the GINECOR working group on behalf of the Spanish Society of Radiation Oncology (SEOR). Given the lack of prospective data on the management of vulvar carcinoma, this document provides an up-to-date review of radiotherapy treatment in vulvar cancer and a series of consensus-based recommendations from a group of experts. Methods A two-round, online modified Delphi study was conducted to reach consensus treatment recommendations in three clinical settings: 1) adjuvant treatment, 2) locally-advanced vulvar cancer (LAVC), and 3) recurrent disease. After the first round, we comprehensively reviewed the available medical literature from peer-reviewed journals to assess and define the evidence-based treatment options. In the second round, participants were asked to indicate their level of agreement with the preliminary recommendations according to the GRADE (Grade of Recommendation, Assessment, Development, and Evaluation) criteria, as follows: strongly agree; agree; neither agree nor disagree; disagree; strongly disagree. Results The main recommendations were as follows: 1) following surgical resection, adjuvant radiotherapy is recommended with the presence of adverse risk factors (primarily positive margins and lymph node involvement); 2) radiotherapy (with or without chemotherapy) should be considered in LAVC; and 3) in recurrent disease, radiotherapy should be individualised on a case-by-case basis. A high level of agreement over 80% was reached. Conclusions In the absence of robust clinical data, these final recommendations may help to select the optimal radiotherapy approach for this relatively rare cancer (AU)

Radiation therapy for vulvar cancer: consensus technical guidelines of the GINECOR working group of the Spanish Society of Radiation Oncology. Part 2: radiotherapy recommendations

Purpose The present consensus statement was developed by the GINECOR working group on behalf of the Spanish Society of Radiation Oncology (SEOR). This document provides an up-to-date review of the technical aspects in radiation treatment of vulvar cancer. Methods A two-round modified Delphi study was conducted to reach consensus on the appropriateness of technical aspects of external beam radiotherapy and brachytherapy. Three clinical scenarios were proposed: adjuvant treatment of vulvar cancer, radiation treatment of locally advanced vulvar carcinoma and locoregional recurrences. After the first round, an extensive analysis of current medical literature from peer-reviewed journal was performed to define evidence-based treatment options. In the second round, participants were asked to indicate their level of agreement with the preliminary recommendations according to the GRADE (Grade of Recommendation, Assessment, Development, and Evaluation) criteria, as follows: strongly agree; agree; neither agree nor disagree; disagree and strongly disagree. Results The main recommendations on external beam radiotherapy and brachytherapy, both in adjuvant setting and local advanced disease are summarized. Recommendations include treatment technique, treatment volume, and doses in target and organs at-risk. Taking into consideration the different clinical scenarios of recurrent disease, the radiation treatment should be individualized. Conclusions In the absence of robust clinical data, these recommendations may help to select the optimal radiotherapy approach for this relatively rare cancer (AU)

Recommendations of the Spanish brachytherapy group of the Spanish Society of Radiation Oncology and the Spanish Society of Medical Physics for interstitial high-dose-rate brachytherapy for gynaecologic malignancies

The present document includes consensus-based recommendations from the Brachytherapy Group (GEB) of the Spanish Society of Radiation Oncology (SEOR) and the Spanish Society of Medical Physics (SEFM) for interstitial high-dose-rate (HDR) brachytherapy (BT) for gynaecologic malignancies. A nine-item survey—which included questions on experience with interstitial BT; indications and technique; applicator type; magnetic resonance imaging (MRI)-based planning; dose; fractionation schedule; and treatment planning—was sent to all radiation oncology departments (n = 174) in Spain in 2021. Responses were received from 36 centres (50% of all centres [n = 72] with a BT unit). The consensus-based recommendations presented here are based on a review of the available literature, professional experience among the group of experts, and in-person discussions held during the annual meeting of these two societies. We describe the results of the survey and the following: indications; contraindications; patient selection; description of applicators; role of imaging in planning; contouring; dose prescription; dosimetric reconstruction; optimisation; and dose indications for cancers of the cervix, vagina, and vulva. The various clinical scenarios in which interstitial BT is used in the treatment of gynaecological tumours are described in detail, including cervix intracavitary/interstitial hybrid HDR-BT; cervix perineal templates/freehand implants; primary vaginal malignancies/vaginal recurrences; and vulvar interstitial implants (AU)

Radiation therapy for vulvar cancer: consensus guidelines of the GINECOR working group of the Spanish Society of Radiation Oncology. Part 1: clinical recommendations.

PURPOSE: The present consensus statement was developed by the GINECOR working group on behalf of the Spanish Society of Radiation Oncology (SEOR). Given the lack of prospective data on the management of vulvar carcinoma, this document provides an up-to-date review of radiotherapy treatment in vulvar cancer and a series of consensus-based recommendations from a group of experts. METHODS: A two-round, online modified Delphi study was conducted to reach consensus treatment recommendations in three clinical settings: 1) adjuvant treatment, 2) locally-advanced vulvar cancer (LAVC), and 3) recurrent disease. After the first round, we comprehensively reviewed the available medical literature from peer-reviewed journals to assess and define the evidence-based treatment options. In the second round, participants were asked to indicate their level of agreement with the preliminary recommendations according to the GRADE (Grade of Recommendation, Assessment, Development, and Evaluation) criteria, as follows: strongly agree; agree; neither agree nor disagree; disagree; strongly disagree. RESULTS: The main recommendations were as follows: 1) following surgical resection, adjuvant radiotherapy is recommended with the presence of adverse risk factors (primarily positive margins and lymph node involvement); 2) radiotherapy (with or without chemotherapy) should be considered in LAVC; and 3) in recurrent disease, radiotherapy should be individualised on a case-by-case basis. A high level of agreement over 80% was reached. CONCLUSIONS: In the absence of robust clinical data, these final recommendations may help to select the optimal radiotherapy approach for this relatively rare cancer.

Radiation therapy for vulvar cancer: consensus technical guidelines of the GINECOR working group of the Spanish Society of Radiation Oncology. Part 2: radiotherapy recommendations.

PURPOSE: The present consensus statement was developed by the GINECOR working group on behalf of the Spanish Society of Radiation Oncology (SEOR). This document provides an up-to-date review of the technical aspects in radiation treatment of vulvar cancer. METHODS: A two-round modified Delphi study was conducted to reach consensus on the appropriateness of technical aspects of external beam radiotherapy and brachytherapy. Three clinical scenarios were proposed: adjuvant treatment of vulvar cancer, radiation treatment of locally advanced vulvar carcinoma and locoregional recurrences. After the first round, an extensive analysis of current medical literature from peer-reviewed journal was performed to define evidence-based treatment options. In the second round, participants were asked to indicate their level of agreement with the preliminary recommendations according to the GRADE (Grade of Recommendation, Assessment, Development, and Evaluation) criteria, as follows: strongly agree; agree; neither agree nor disagree; disagree and strongly disagree. RESULTS: The main recommendations on external beam radiotherapy and brachytherapy, both in adjuvant setting and local advanced disease are summarized. Recommendations include treatment technique, treatment volume, and doses in target and organs at-risk. Taking into consideration the different clinical scenarios of recurrent disease, the radiation treatment should be individualized. CONCLUSIONS: In the absence of robust clinical data, these recommendations may help to select the optimal radiotherapy approach for this relatively rare cancer.

Recommendations of the Spanish brachytherapy group of the Spanish Society of Radiation Oncology and the Spanish Society of Medical Physics for interstitial high-dose-rate brachytherapy for gynaecologic malignancies.

The present document includes consensus-based recommendations from the Brachytherapy Group (GEB) of the Spanish Society of Radiation Oncology (SEOR) and the Spanish Society of Medical Physics (SEFM) for interstitial high-dose-rate (HDR) brachytherapy (BT) for gynaecologic malignancies. A nine-item survey-which included questions on experience with interstitial BT; indications and technique; applicator type; magnetic resonance imaging (MRI)-based planning; dose; fractionation schedule; and treatment planning-was sent to all radiation oncology departments (n = 174) in Spain in 2021. Responses were received from 36 centres (50% of all centres [n = 72] with a BT unit). The consensus-based recommendations presented here are based on a review of the available literature, professional experience among the group of experts, and in-person discussions held during the annual meeting of these two societies. We describe the results of the survey and the following: indications; contraindications; patient selection; description of applicators; role of imaging in planning; contouring; dose prescription; dosimetric reconstruction; optimisation; and dose indications for cancers of the cervix, vagina, and vulva. The various clinical scenarios in which interstitial BT is used in the treatment of gynaecological tumours are described in detail, including cervix intracavitary/interstitial hybrid HDR-BT; cervix perineal templates/freehand implants; primary vaginal malignancies/vaginal recurrences; and vulvar interstitial implants.

HDR brachytherapy in keratinocyte skin carcinomas - Single center experience with analysis of clinical, dosimetric, and radiobiological factors in acute skin toxicity.

PURPOSE: Radiotherapy techniques have been utilized to treat keratinocyte skin carcinoma (KSC). The objective of this study was to report the results of patients with KSC treated with HDR brachytherapy, with a variety of techniques and applicators. A statistical analysis of clinical, radiobiological, and technical factors has been made to analyze those factors related to skin acute toxicity, focused on acute epithelitis G3. METHODS AND MATERIALS: Between February 2005 and August 2020, 93 patients with 120 histologically proven KSC have been treated in our Institution. BT treatment has been performed using superficial BT/plesiotherapy (Valencia applicator (22%), flaps (48%), customized molds (4%) or interstitial techniques (26%)). The indications of BT were primary/definitive in 38 treatments (32%) or adjuvant/postoperative in 82 (68%). In 14 (17%) of the 82 operated patients a skin graft. Mean comparison t tests were performed for quantitative variables, and percentage comparison Chi2 tests for qualitative. Multivariate binomial logistic regression models were done. RESULTS: Median follow-up was 36.5 months (range 5-141). Local control was achieved in 110 treatments (92%). Acute toxicity, dermatitis, was G1 7%; G2, 57% and G3 38%. The main factors statistically associated to the appearance of dermatitis G3 were the total dose, the volume treated, and the use of manufactured flaps. The main protective factor against dermatitis G3 was implant of skin graft. CONCLUSIONS: In KSC BT the use of manufactured flap is accompanied by greater EG3, only with a relationship with the volume of treatment and total dose.

Salvage brachytherapy for locally-recurrent prostate cancer after radiation therapy: A comparison of efficacy and toxicity outcomes with high-dose rate and low-dose rate brachytherapy.

BACKGROUND: Brachytherapy (BT) is widely used for salvage therapy in patients with biochemical failure (BF) after radiotherapy for prostate cancer (PCa). Although low-dose-rate (LDR) and high-dose-rate (HDR) BT are both used for salvage therapy, it is not clear whether there are any differences between these two approaches in terms of efficacy or toxicity in this setting. Therefore, we review the institutional experience of the members of the Urological Tumour Working Group (URONCOR) of the Spanish Society of Radiation Oncology (SEOR) to compare these two techniques. METHODS AND MATERIALS: Between 2001 and 2016, 119 patients with biopsy-proven, locally-recurrent PCa underwent salvage BT (LDR, n = 44; HDR, n = 75) after primary radiotherapy. Relapse-free survival (RFS) and cause-specific survival (CSS) after salvage therapy were analyzed. Toxicity was assessed according to the RTOG scale. RESULTS: Median follow-up after salvage BT was 52 months. Overall, the 5-year prostate-specific antigen (PSA) RFS rate was 71% (95% CI, 65.9%-75.9%). No significant between-group differences in RFS were observed (p = 0.063). Five-year CSS for the LDR- and HDR-BT groups were 96.5% and 93%, respectively. Overall, 38 patients (32%) developed biochemical progression (Phoenix definition) after salvage BT: 14 patients (32%) in the LDR group and 24 (32.5%) in the HDR group. On the multivariate analysis, the following variables were significantly associated with progression, time to BF from primary radiotherapy <30 months (p = 0.014); and post-salvage nadir PSA (p = 0.000). There were no significant between-group differences in toxicity. Overall, there were 13 cases of urethral stricture, 22 cases of urinary incontinence, and 13 cases of haematuria. Toxicity ≥grade 3 was observed in 23.5% of patients. CONCLUSIONS: These findings show that both HDR-BT and LDR-BT yield comparable efficacy and toxicity outcomes in patients undergoing salvage treatment for locally-recurrent prostate cancer after primary radiotherapy. Predictors of worse outcomes after salvage BT were post-salvage nadir PSA and time to BF from initial radiotherapy.

GEC-ESTRO ACROP recommendations in skin brachytherapy.

PURPOSE: The aim of this publication is to compile available literature data and expert experience regarding skin brachytherapy (BT) in order to produce general recommendations on behalf of the GEC-ESTRO Group. METHODS: We have done an exhaustive review of published articles to look for general recommendations. RESULTS: Randomized controlled trials, systemic reviews and meta-analysis are lacking in literature and there is wide variety of prescription techniques successfully used across the radiotherapy centers. BT can be delivered as superficial application (also called contact BT or plesiotherapy) or as interstitial for tumours thicker than 5 mm within any surface, including very irregular. In selected cases, particularly in tumours located within curved surfaces, BT can be advantageous modality from dosimetric and planning point of view when compared to external beam radiotherapy. The general rule in skin BT is that the smaller the target volume, the highest dose per fraction and the shortest overall length of treatment can be used. CONCLUSION: Skin cancer incidence is rising worldwide. BT offers an effective non-invasive or minimally invasive and relative short treatment that particularly appeals to elder and frail population.

Interobserver variability in rectum contouring in high-dose-rate brachytherapy for prostate cancer: A multi-institutional prospective analysis.

PURPOSE: The aim of this study was to evaluate the interobserver variability (IOV) of rectum contouring, and its dosimetric consequences, for high-dose-rate brachytherapy in patients with prostate cancer across multiple institutions. METHODS AND MATERIALS: Five radiation oncologists contoured rectums in 10 patients on transperineal ultrasound image sets after establishing a delineation consensus. The D0.1cc, D1cc, and D2cc rectum volume parameters were determined. The mean, standard deviation, and range of each dose-volume histogram parameter were evaluated for each patient. The IOV was determined using the coefficient of variation, and the dosimetric impacts on the total dose were analyzed by estimating the biologically equivalent dose (EQD2α/ß = 3). RESULTS: The interobserver coefficients of variation (±standard deviation) for the reported D0.1cc, D1cc, and D2cc were 5 ± 1.84%, 4 ± 1.26%, and 4 ± 1.33%, respectively. As for the impact on the total dose, the mean dose differences for D0.1cc, D1cc, and D2cc were 10 Gy, 7.3 Gy, and 6.6 Gy, respectively. CONCLUSIONS: The D2cc is robust as evident by the low IOV (<5%). However, some variability ranges almost overlap with the clinical threshold level, which may present dosimetric and clinical complications. General rectal contouring guidelines for prostate high-dose-rate brachytherapy are desirable to reduce discrepancies in delineation.

Skin surface brachytherapy: A survey of contemporary practice patterns.

PURPOSE: The aim of this study was to define current patterns of care among radiation oncologists who use skin surface brachytherapy for the treatment of cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) in academic and community settings. METHODS AND MATERIALS: A 30-question electronic survey was administered to clinician members of the American Brachytherapy Society. The respondents were asked to provide details regarding their clinical practice and their approach to skin surface brachytherapy. RESULTS: A total of 16 surveys were returned. Among the respondents, aggregate experience varied from 8 to 1800 cases. Most preferred brachytherapy over external beam radiation because of shorter treatment course, conformality of treatment for irregular or curved targets, and shallow dose deposition. Of the total, 60% of respondents routinely estimated lesion depth via ultrasound before initiating treatment. Treatment margin on gross disease varied widely (range, 3-15 mm; median, 5 mm). Hypofractionation was the preferred dose schedule. Prescribed doses ranged from 30 Gy in five fractions to 64 Gy in 32 fractions (EQD2, 40 Gy-65 Gy). There was a tendency to increase the number of fractions for larger targets, although some used the same fractionation regardless of anatomic location or lesion size. There was no consensus on dosimetric constraints, and some respondents reported cases of severe toxicity, particularly when treating the pretibial skin. CONCLUSIONS: This pattern of care study suggests that skin brachytherapy can be a convenient and safe tool for treatment of BCC and cSCC. Prospective trials and the development of expert consensus guidelines would be beneficial for optimizing skin surface brachytherapy and reducing practice variation.

Development and clinical implementation of a new template for MRI-based intracavitary/interstitial gynecologic brachytherapy for locally advanced cervical cancer: from CT-based MUPIT to the MRI compatible Template Benidorm. Ten years of experience.

PURPOSE: To study outcome and toxicity in 59 patients with locally advanced cervix carcinoma treated with computed tomography (CT)-based Martinez universal perineal interstitial template (MUPIT) and the new magnetic resonance imaging (MRI)-compatible template Benidorm (TB). MATERIAL AND METHODS: From December 2005 to October 2015, we retrospectively analyzed 34 patients treated with MUPIT and 25 treated with the TB. Six 4 Gy fractions were prescribed to the clinical target volume (CTV) combined with external beam radiotherapy (EBRT). The organs at risk (OARs) and the CTV were delineated by CT scan in the MUPIT implants and by MRI in the TB implants. Dosimetry was CT-based for MUPIT and exclusively MRI-based for TB. Dose values were biologically normalized to equivalent doses in 2 Gy fractions (EQD2). RESULTS: Median CTV volumes were 163.5 cm3 for CT-based MUPIT (range 81.8-329.4 cm3) and 91.9 cm3 for MRI-based TB (range 26.2-161 cm3). Median D90 CTV (EBRT + BT) was 75.8 Gy for CT-based MUPIT (range 69-82 Gy) and 78.6 Gy for MRI-based TB (range 62.5-84.2 Gy). Median D2cm3 for the rectum was 75.3 Gy for CT-based MUPIT (range 69.8-132.1 Gy) and 69.9 Gy for MRI-based TB (range 58.3-83.7 Gy). Median D2cm3 for the bladder was 79.8 Gy for CT-based MUPIT (range 71.2-121.1 Gy) and 77.1 Gy for MRI-based TB (range 60.5-90.8 Gy). Local control (LC) was 88%. Overall survival (OS), disease free survival (DFS), and LC were not statistically significant in either group. Patients treated with CT-based MUPIT had a significantly higher percentage of rectal bleeding G3 (p = 0.040) than those treated with MRI-based TB, 13% vs. 2%. CONCLUSIONS: Template Benidorm treatment using MRI-based dosimetry provides advantages of MRI volume definition, and allows definition of smaller volumes that result in statistically significant decreased rectal toxicity compared to that seen with CT-based MUPIT treatment.

A new template for MRI-based intracavitary/interstitial gynecologic brachytherapy: design and clinical implementation.

PURPOSE: To describe the potential clinical use of a new brachytherapy applicator for gynecological tumors, with special attention to locally advanced cervical carcinoma. This device allows the combination of intracavitary radiotherapy and MRI-compatible transperineal interstitial needles. The design of this template addresses the disadvantages of currently commercially available templates: the inability of the intracavitary component to reach deep into the cervix (MUPIT), and the MRI-incompatibility of these templates (MUPIT and Syed), which necessitates use of CT imaging for the dosimetry. MATERIAL AND METHODS: The newly developed Benidorm Template applicator allows titanium needles in a template with straight and angled holes to provide different angles of divergence to be used with currently existing MRI-compatible intrauterine tubes. It can provide total coverage of the craniocaudal and lateral extension of the tumor (intrautherus, parametrial, and paravaginal). This method is mainly indicated in advanced cervical carcinoma with bulky parametrial invasion (medial or distal), with bulky primary disease that responds poorly to external beam radiotherapy extensive paravaginal involvement (tumor thickness greater than 0.5 cm) extending to the middle or lower third of the vagina, or for disease that has invaded the bladder or rectum (stage IVA). RESULTS: Between April 2013 until December 2014, we treated 15 patients with locally advanced cervical carcinoma employing the Benidorm Template. The median dose at D90 for the CTV was 79.8 Gy (71.5-89.9 Gy), at D2cc for the bladder it was 77.6 Gy (69.8-90.8 Gy), and at D2cc for the rectum it was 71.9 Gy (58.3-83.7 Gy). Values expressed in EQD2, assuming α/ß of 10 for CTV and 3 for OAR. CONCLUSIONS: This new applicator allows the use of MRI-based dosimetry, thus providing the advantages of MRI volume definition. As such, it facilitates determination of complete intracavitary and interstitial CTV coverage and the sparing of normal tissues.

Depth determination of skin cancers treated with superficial brachytherapy: ultrasound vs. histopathology.

PURPOSE: The purpose of this study is to compare high frequency ultrasonography (HFUS) and histpathologic assessment done by punch biopsy in order to determine depth of basal cell carcinoma (BCC), in both superficial and nodular BCCs prior to brachytherapy treatment. MATERIAL AND METHODS: This study includes 20 patients with 10 superficial and 10 nodular BCCs. First, punch biopsy was done to confirm the diagnosis and to measure tumour depth (Breslow rate). Subsequently, HFUS was done to measure tumour depth to search for correlation of these two techniques. RESULTS: Neither clear tendency nor significance of the punch biopsy vs. HFUS depth determination is observed. Depth value differences with both modalities resulted patient dependent and then consequence of its uncertainty. Conceptually, HFUS should determine the macroscopic lesion (gross tumour volume - GTV), while punch biopsy is able to detect the microscopic extension (clinical target volume - CTV). Uncertainties of HFUS are difficult to address, while punch biopsy is done just on a small lesion section, not necessarily the deepest one. CONCLUSIONS: According to the results, HFUS is less accurate at very shallow depths. Nodular cases present higher depth determination differences than superficial ones. In our clinical practice, we decided to prescribe at 3 mm depth when HFUS measurements give depth lesion values smaller than this value.

Current opinion in cervix carcinoma.

We review the current status of the conventional therapeutical approaches of cervix carcinoma. Radical hysterectomy remains as the main stone in early stages and play an important role in relapses. Radiotherapy plays an important role in early and advance disease. New techniques and image expand indications and treatment possibilities. Chemotherapy platinum based with radiation therapy goes on being the standard treatment in advanced tumours or non surgical candidates. New systemic strategies are being explored in clinical trials.