Status of head and neck brachytherapy in Spain in 2022

Purpose Brachytherapy (BT) has been used for many years for disease control in tumours of the head and neck area (H&N). It is currently performed with high dose rate (HDR) or pulsed dose rate (PDR), but its use has been reduced due to the implementation of new non-invasive external beam radiotherapy techniques such as intensity modulation (IMRT) and volumetric modulated arc therapy (VMAT) and the improvement of surgical techniques. Methods The Spanish Brachytherapy Group (GEB) has carried out a survey to find out the number of centres in Spain that continue to use BT in H&N and its indications and expectations for the future. Results The results were presented at the XX GEB Consensus Meeting held on October 21, 2022, in Valencia (Spain) and it was confirmed that, although there are fewer and fewer centres that use BT in H&N, there are still units with extensive experience in this technique that should be positioned as referral centres. Conclusion It is necessary to carry out continuous work with other specialities involved, such as H&N surgeons, and other radiation oncologists, to improve the training of residents, both oncologists and medical physicists (AU)

Status of head and neck brachytherapy in Spain in 2022.

PURPOSE: Brachytherapy (BT) has been used for many years for disease control in tumours of the head and neck area (H&N). It is currently performed with high dose rate (HDR) or pulsed dose rate (PDR), but its use has been reduced due to the implementation of new non-invasive external beam radiotherapy techniques such as intensity modulation (IMRT) and volumetric modulated arc therapy (VMAT) and the improvement of surgical techniques. METHODS: The Spanish Brachytherapy Group (GEB) has carried out a survey to find out the number of centres in Spain that continue to use BT in H&N and its indications and expectations for the future. RESULTS: The results were presented at the XX GEB Consensus Meeting held on October 21, 2022, in Valencia (Spain) and it was confirmed that, although there are fewer and fewer centres that use BT in H&N, there are still units with extensive experience in this technique that should be positioned as referral centres. CONCLUSION: It is necessary to carry out continuous work with other specialities involved, such as H&N surgeons, and other radiation oncologists, to improve the training of residents, both oncologists and medical physicists.

Association of persistent morbidity after radiotherapy with quality of life in locally advanced cervical cancer survivors.

PURPOSE: To quantify the association of persistent morbidity with different aspects of quality of life (QOL) in locally advanced cervical cancer (LACC) survivors. MATERIAL AND METHODS: Longitudinal outcome from the EMBRACE-I study was evaluated. Patient-reported symptoms and QOL were prospectively scored (EORTC-C30/CX24) at baseline and regular follow-ups. Physician-assessed symptoms were also reported (CTCAEv.3). Persistent symptoms were defined if present in at least half of the follow-ups. QOL items were linearly transformed into a continuous scale. Linear mixed-effects models (LMM) were applied to evaluate and quantify the association of persistent symptoms with QOL. Overall QOL deterioration was evaluated by calculating the integral difference in QOL over time obtained with LMM for patients without and with persistent symptoms. RESULTS: Out of 1416 patients enrolled, 741 with baseline and ≥ 3 late follow-ups were analyzed (median 59 months). Proportions of persistent EORTC symptoms ranged from 21.8 % to 64.9 % (bowel control and tiredness). For CTCAE the range was 11.3-28.6 % (limb edema and fatigue). Presence of any persistent symptom was associated with QOL, although with varying magnitude. Role functioning and Global health/QOL were the most impaired aspects. Fatigue and pain showed large differences, with reductions of around 20 % for most of the QOL aspects. Among organ-related symptoms, abdominal cramps showed the largest effect. CONCLUSION: Persistent symptoms are associated with QOL reductions in LACC survivors. Organ-related symptoms showed smaller differences than general symptoms such as fatigue and pain. In addition to optimizing treatment to minimize organ-related morbidity, effort should be directed towards a more comprehensive and targeted morbidity management.

Phase II Study of ENZAlutamide Combined With Hypofractionated Radiation Therapy (ENZART) for Localized Intermediate Risk Prostate Cancer.

Background: Intermediate-risk prostate cancer (PCa) is usually treated by a combination of external beam radiation therapy (EBRT) and a short course of androgen deprivation therapy (ADT). ADT is associated with multiple side effects, including weight gain, loss of libido, and hot flashes. In contrast, anti-androgen monotherapy is generally better tolerated in spite of higher rates of gynecomastia. Objective: This study assessed the effectiveness of enzalutamide monotherapy combined with hypofractionated EBRT (Hypo-EBRT) for treating intermediate risk prostate cancer. Method: This trial was a multicenter, open-label phase II study of 6 months of enzalutamide monotherapy combined with Hypo-EBRT for intermediate-risk prostate cancer. Hypo-EBRT was initiated 8-12 weeks after initiating enzalutamide. The primary endpoint was PSA decline >80% measured at the 25th week of enzalutamide administration. Secondary end-points included assessment of toxicity, changes in anthropomorphic body measurements, sexual hormones, and metabolic changes. Results: Sixty-two patients were included in the study from January 2018 to February 2020. A PSA decline of >80% was observed in all evaluable patients at the end of enzalutamide treatment and 92% achieved PSA values under 0.1 ngr/ml. All patients remain in PSA response (<80% reduction of the initial values) 6 months after the end of enzalutamide treatment. The most frequent adverse events were hypertension, asthenia, and gynecomastia. There were no significant changes in bone density, body mass index (BMI), or patient-reported outcomes (PROs). Conclusion: Enzalutamide monotherapy is very effective along with hEBRT in reducing PSA levels for patients with intermediate-risk prostate cancer. Longer follow-up is needed to confirm the potential use of this combination in future randomized trials.

Review on Treatment Planning Systems for Cervix Brachytherapy (Interventional Radiotherapy): Some Desirable and Convenient Practical Aspects to Be Implemented from Radiation Oncologist and Medical Physics Perspectives.

Intracavitary brachytherapy (BT, Interventional Radiotherapy, IRT), plays an essential role in the curative intent of locally advanced cervical cancer, for which the conventional approach involves external beam radiotherapy with concurrent chemotherapy followed by BT. This work aims to review the different methodologies used by commercially available treatment planning systems (TPSs) in exclusive magnetic resonance imaging-based (MRI) cervix BT with interstitial component treatments. Practical aspects and improvements to be implemented into the TPSs are discussed. This review is based on the clinical expertise of a group of radiation oncologists and medical physicists and on interactive demos provided by the software manufacturers. The TPS versions considered include all the new tools currently in development for future commercial releases. The specialists from the supplier companies were asked to propose solutions to some of the challenges often encountered in a clinical environment through a questionnaire. The results include not only such answers but also comments by the authors that, in their opinion, could help solve the challenges covered in these questions. This study summarizes the possibilities offered nowadays by commercial TPSs, highlighting the absence of some useful tools that would notably improve the planning of MR-based interstitial component cervix brachytherapy.

Severity and Persistency of Late Gastrointestinal Morbidity in Locally Advanced Cervical Cancer: Lessons Learned From EMBRACE-I and Implications for the Future.

PURPOSE: The purpose was to evaluate patient- and treatment-related risk factors for physician-assessed and patient-reported gastrointestinal (GI) symptoms after radio(chemo)therapy and image guided adaptive brachytherapy in locally advanced cervical cancer. METHODS AND MATERIALS: Of 1416 patients from the EMBRACE-I study, 1199 and 1002 were prospectively evaluated using physician-assessed (Common Terminology Criteria for Adverse Events [CTCAE]) and patient-reported (European Organization for Research and Treatment of Cancer [EORTC]) GI symptoms, respectively. CTCAE severe grade (grade [G] ≥3) events were pooled according to the location in the GI tract (anus/rectum, sigmoid, and colon/small bowel). CTCAE G ≥2 and EORTC "very much" and "quite a bit" plus "very much" scores (≥ "quite a bit") were analyzed for individual symptoms with Cox regression. Logistic regression was used for persistent G ≥1 and EORTC ≥ "quite a bit" symptoms, defined if present in at least half of follow-ups. RESULTS: The incidence of G ≥3 events was 2.8%, 1.8%, and 2.3% for G ≥3 anus/rectum, sigmoid, and colon/small bowel events, respectively. Among G ≥2 symptoms, diarrhea and flatulence were the most prevalent (8.5% and 9.9%, respectively). Among patient-related factors, baseline morbidity, increasing age, smoking status, and low body mass index were associated with GI symptoms to varying degrees. Among treatment-related factors, rectum D2cm3 and the International Commission on Radiation Units and Measurements recto-vaginal reference point (ICRU RV-RP) correlated with G ≥3 anus/rectum events and moderate/persistent diarrhea, proctitis, bleeding, abdominal cramps, and difficulty in bowel control. Bowel D2cm3 correlated with G ≥3 sigmoid and colon/small bowel events and moderate/persistent diarrhea and flatulence. For external beam radiation therapy (EBRT), prescription dose correlated with G ≥3 anus/rectum, diarrhea, and difficulty in bowel control. Patients with large lymph-node boost (V57Gy) were at higher risk for G ≥3 sigmoid events, moderate/persistent diarrhea, proctitis, and cramps. CONCLUSIONS: The analysis showed that both EBRT and image guided adaptive brachytherapy contribute to GI symptoms after locally advanced cervical cancer treatment. Rectum D2cm3, ICRU RV-RP , and bowel D2cm3 are risk factors for GI morbidity. The risk for various symptoms was lower with an EBRT prescription of 45 Gy than 50 Gy and increased with larger V57Gy.

Impact of Vaginal Symptoms and Hormonal Replacement Therapy on Sexual Outcomes After Definitive Chemoradiotherapy in Patients With Locally Advanced Cervical Cancer: Results from the EMBRACE-I Study.

PURPOSE: To evaluate patient-reported sexual outcomes after chemoradiation therapy and image-guided adaptive brachytherapy for locally advanced cervical cancer in the observational, prospective, multicenter EMBRACE-I study. METHODS AND MATERIALS: Sexual outcomes were assessed prospectively with the European Organization for Research and Treatment of Cancer Qualify of Life Questionnaire (EORTC-QLQ-CX24) at baseline and follow-up. Crude incidence and prevalence rates of sexual activity, vaginal functioning problems (dryness, shortening, tightening, pain during intercourse), and sexual enjoyment were evaluated. Associations between pain during intercourse and vaginal functioning problems or sexual enjoyment were calculated, pooling observations over all follow-ups (Spearman correlation coefficient). In patients who were frequently sexually active (≥50% of follow-ups), the effects of regular hormonal replacement therapy (HRT) on vaginal functioning problems were evaluated (Pearson χ2). RESULTS: The analysis involved 1045 patients with a median follow-up of 50 months. Sexual activity was reported by 22% of patients at baseline and by 40% to 47% of patients during follow-up (prevalence rates). Vaginal functioning problems in follow-up were dryness (18%-21%), shortening (15%-22%), tightening (16%-22%), pain during intercourse (9%-21%), and compromised enjoyment (37%-47%). Pain during intercourse was significantly associated with vaginal tightening (r = 0.544), shortening (r = 0.532), and dryness (r = 0.408) and negatively correlated with sexual enjoyment (r = -0.407). Regular HRT was associated with significantly less vaginal dryness (P = .015), shortening (P = .024), pain during intercourse (P = .003), and borderline higher sexual enjoyment (P = .062). CONCLUSIONS: Vaginal functioning problems are associated with pain and compromised sexual enjoyment. Further effort is required for the primary prevention of vaginal morbidity with dose optimization and adaptation. Secondary prevention strategies, including HRT for vaginal and sexual health after radiation therapy in locally advanced cervical cancer, should be considered and sexual rehabilitation programs should be developed further.

Risk Factors for Late Persistent Fatigue After Chemoradiotherapy in Patients With Locally Advanced Cervical Cancer: An Analysis From the EMBRACE-I Study.

PURPOSE: This study aimed to evaluate patient- and treatment-related risk factors for late persistent fatigue within the prospective, multicenter EMBRACE-I study. METHODS AND MATERIALS: Fatigue was prospectively assessed (Common Terminology Criteria for Adverse Events, version 3) at baseline and during regular follow up in 993 patients with locally advanced cervical cancer after treatment with chemoradiotherapy and magnetic resonance imaging-guided brachytherapy. Risk factors for baseline and late persistent fatigue were evaluated with multivariable logistic regression. Late persistent fatigue was defined when either grade ≥1 or ≥2 was scored in at least half of the follow ups. RESULTS: The median follow-up time was 57 months. Baseline fatigue grade ≥1/≥2 (35.8%/6.3%, respectively) was associated with preexisting comorbidities, World Health Organization performance status, being underweight, severe pain, and tumor volume. Late persistent grade ≥1/≥2 fatigue (36.3%/5.8%, respectively) was associated with patient-related factors (baseline fatigue, younger age, obesity) along with the size of irradiated volumes and the level of radiation doses from external beam radiation therapy (EBRT) and brachytherapy (EBRT: V43Gy, V57Gy; EBRT + brachytherapy: V60Gy equivalent dose in 2-Gy fractions). Large-volume lymph node (LN) boost increased the risk for late persistent fatigue grade ≥2 by 18% and 5% in patients with and without baseline fatigue, respectively, compared with no LN boost. The risk for late persistent fatigue grade ≥1 increased by 7% and 4% with V43Gy <2000 cm³ versus >3000 cm³ in patients with and without baseline fatigue, respectively. Late persistent grade ≥1 fatigue occurred in 13% of patients without late persistent organ-related symptoms (gastrointestinal, genitourinary, and vaginal) versus 34% to 43%, 50% to 58%, and 73% in patients suffering from persistent symptoms involving 1, 2, or 3 organs, respectively. CONCLUSIONS: Late persistent fatigue occurs in a considerable number of patients after chemoradiotherapy, and is associated with patient-related factors, the size of volumes irradiated to intermediate and high EBRT and brachytherapy doses, and other persistent organ-related morbidity. These findings support the importance of ongoing efforts to better tailor the target dose and reduce irradiation of healthy tissue without compromising target coverage, using highly conformal EBRT and brachytherapy techniques.

Results of image guided brachytherapy for stage IB cervical cancer in the RetroEMBRACE study.

OBJECTIVE: Multiple treatment options are used in early local-stage cervical cancer, including combinations of surgery with neoadjuvant/adjuvant radiotherapy and chemotherapy. Our aim was to determine the outcome for definitive chemoradiation with image guided brachytherapy (IGBT). METHODS: FIGO1994 staging system was used in our study. We included 123 patients with stage IB cervical cancer, treated at 12 centers with external beam radiotherapy (EBRT) ± Chemotherapy and IGBT. Three- and 5-year actuarial local control (LC), pelvic control (PC), overall survival (OS), cancer-specific survival (CSS) and late morbidity (CTCAE v 3.0) were computed. RESULTS: Median age was 48 (23-82) years. FIGO1994 stage distribution was: IB1 68% and IB2 32%; 41% of the entire cohort had nodal metastases and 73% squamous-cell carcinoma. MRI-based tumor size was >40 mm in 63%. Median EBRT dose was 45 (40-50) Gy; 84% received chemotherapy. At IGBT, mean CTV-HR D90 was 93 ± 17 Gy (EQD210). D2cc for bladder was 76 ± 14 Gy, rectum 66 ± 11 Gy, sigmoid 66 ± 10 Gy, bowel 67 ± 7 Gy (EQD23). At 43-months median follow-up, 9% of patients had systemic, 6% paraaortic, 3% pelvic-nodal and 2% local failure. Five-year LC was 98%, PC 96%, CSS 90%, OS 83%. Intestinal G3--4 morbidity was 8%, urinary 7% and vaginal 0%. CONCLUSIONS: Chemoradiation with IGBT for FIGO1994 stage IB cervical cancer leads to excellent loco-regional control with limited morbidity. In IB node-negative disease, it can be regarded equivalent to surgery in terms of oncologic outcome. In tumors with unfavorable pre-treatment characteristics, chemoradiation is the first choice to avoid combining surgery with adjuvant therapy.

Persistence of Late Substantial Patient-Reported Symptoms (LAPERS) After Radiochemotherapy Including Image Guided Adaptive Brachytherapy for Locally Advanced Cervical Cancer: A Report From the EMBRACE Study.

PURPOSE: This report describes the persistence of late substantial treatment-related patient-reported symptoms (LAPERS) in the multi-institutional EMBRACE study on magnetic resonance image guided adaptive brachytherapy in locally advanced cervical cancer (LACC). METHODS AND MATERIALS: Patient-reported symptoms (European Organization for Research and Treatment of Cancer [EORTC]-C30/CX24) and physician-assessed morbidity (Common Terminology Criteria for Adverse Events [CTCAE], version 3.0) were assessed at baseline and regular timepoints during follow-up. Patients with sufficient EORTC follow-up (baseline and ≥3 late follow-up visits) were analyzed. LAPERS events were defined as the presence of substantial EORTC symptoms (quite a bit/very much) for at least half of the assessments (persistence) and progression beyond baseline condition (treatment-related). For each EORTC symptom, the ratio between LAPERS rates and crude incidence rates of substantial symptoms was calculated to represent the proportion of symptomatic patients with persisting symptoms. For 9 symptoms with a corresponding EORTC/CTCAE assessment, the overlap of LAPERS and severe morbidity events (grades 3-5) was evaluated. RESULTS: Of 1047 patients with EORTC available, 741 had sufficient follow-up for the LAPERS analyses. The median follow-up was 59 months (interquartile range, 42-70 months). Across all symptoms, the proportion of patients with LAPERS events (LAPERS rates) was in median 4.6% (range, 0.0% vaginal bleeding to 20.4% tiredness). Urinary frequency, neuropathy, fatigue, insomnia, and menopausal symptoms revealed LAPERS rates of >10%. Vomiting, blood in stool, urinary pain/burning, and abnormal vaginal bleeding displayed LAPERS rates of <1%. A median of 19% of symptomatic patients (interquartile range, 8.0%-28.5%) showed persistent long-term symptoms (LAPERS events). In symptoms with a corresponding EORTC/CTCAE assessment, 12% of LAPERS events were accompanied by a severe CTCAE event. CONCLUSIONS: Within this large cohort of survivors of LACC, a subgroup of patients with persistent symptoms (LAPERS events) was identified. For symptoms with a corresponding EORTC/CTCAE assessment, the vast majority of LAPERS events occurred in patients without corresponding severe physician-assessed morbidity. These findings emphasize the importance of distinguishing between transient and persisting symptoms in the aftercare of LACC survivors.

Evaluation of the impact of EMBRACE II protocol in Spanish centers, with a large cohort of patients using a ranking index.

PURPOSE: The aim of this paper was to assess development of high-dose-rate (HDR) cervix brachytherapy (BT) implants in three Spanish institutions before and after introduction of EMBRACE II protocol. MATERIAL AND METHODS: 392 patients from three different institutions, treated between 2009 and 2019 were analyzed. D90 of high-risk clinical target volume (HR-CTV) and D2cc of organs at risk (OARs) of all patients were collected. Statistical distribution was analyzed for two different periods of time: before and after EMBRACE II publication. Index I was applied based on collected dosimetric quantities (D90 and D2cc) to enhance equilibrium between HR-CTV coverage and doses to OARs. Variation in dosimetry and index depending on CTV and technique used (IC vs. IC/IT) were also evaluated. RESULTS: Adaptation of institutions to EMBRACE II protocol resulted in a statistically significant increase of D90 HR-CTV (Institution 1; p < 0.00001) or decrease of D2cc OARs (Institution 2; p < 0.04). Increase in the use of interstitial component showed higher coverage of HR-CTV for Institution 3 (p = 0.03), and lower doses to OARs for the same coverage of HR-CTV at Institution 2 (p-OARs < 0.03). Even though index I was only significantly different between periods for Institution 1 (p < 0.0000001), it was able to show a reduction of dose variability related to higher expertise and higher interstitial component. CONCLUSIONS: Depending on local protocol before EMBRACE II, the adaptation through increasing interstitial component and physician and physicist training, resulted in a significant increase of HR-CTV doses or reduction of OARs doses. Index I was able to describe an evolution of equilibrium between CTV coverage and OARs' sparing.

Change in Patterns of Failure After Image-Guided Brachytherapy for Cervical Cancer: Analysis From the RetroEMBRACE Study.

PURPOSE: Image guided adaptive brachytherapy (IGABT) for cervical cancer improves pelvic control and survival across all stages. Improvement in pelvic control is larger in advanced stages, but improvement in survival is similar across stages. This paper analyzes the patterns of failure in the RetroEMBRACE cohort to investigate this discrepancy. METHODS AND MATERIALS: 731 patients from 12 institutions treated with chemoradiation therapy and magnetic resonance imaging or computed tomography-based IGABT were evaluated. The pattern of failure at time of first relapse was analyzed. RESULTS: Three hundred twenty-five failures (single and synchronous) occurred in 222 of 731 patients (30%). Among the 325 failures, 9% were local and 6% regional. Pelvic (local or regional) failures made up 13%, paraaortic node (PAN) 9%, systemic 21%, and distant (systemic + PAN) 24%. Of the 222 patients with treatment failure, 21% had pelvic failure alone, 57% had distant failure alone, and 23% had both pelvic and distant failure. Of all failures that occurred, 40% to 50% occurred in the first year, with a further 20% to 30% occurring in the second year. Although local, regional, and PAN failure tended to plateau after year 3, systemic failure continued to occur up to year 10. CONCLUSIONS: Implementation of IGABT has changed the patterns of relapse after chemoradiation therapy for cervical cancer. The predominant failure after IGABT is systemic, whereas the predominant failure with conventional brachytherapy is pelvic. Effective treatments to eradicate micrometastases in PAN and distant organs are needed in addition to IGABT and chemoradiation therapy to maximize local, regional, PAN, and systemic control and improve survival.

Para-aortic plus pelvic lymphadenectomy in locally advanced cervical cancer: A single institutional experience.

OBJECTIVE: The aim of the study is to assess the safety and efficacy of transperitoneal laparoscopic para-aortic and pelvic lymphadenectomy in the setting of surgical staging of patients with locally advanced cervical cancer (LACC), and to analyse the prognostic value and impact of this staging on the survival prognosis of this condition. STUDY DESIGN: Data from 67 patients with LACC who underwent transperitoneal laparoscopic para-aortic and pelvic lymphadenectomy and who received chemo-radiation therapy were retrospectively analysed. RESULTS: Metastatic lymph nodes (LN) were identified in 32 patients (47.7%), 20 (29.8%) had metastatic LN in the pelvic area and 12 (17.9%) had metastatic LN in the pelvic and para-aortic area. There were no skip metastases in the para-aortic area. After a median follow-up of 54.6 months (5-122.2 months), the 5-year local control and disease-free survival (DFS) rates for the whole group were 91.1% and 60.5% respectively. The five-year DFS for patients without LN metastasis was 86.4%, while for patients with pelvic LN metastases or pelvic and para-aortic metastases was 34.2% and 24.2% respectively (p < 0.001). The five-year overall survival (OS) for the whole group was 67.3%. The mortality rate in patients with para-aortic nodal metastases was increased compared to patients with negative nodes (5-year OS 21.3% vs 81.6% respectively, p = 0.005), but the OS rate was similar in patients with negative nodes and those with only pelvic nodes affected (5-year OS 81.6% vs 70.8% respectively, p = 0.380). This approach allowed the modification of the initial treatment plan in the para-aortic area in 13.4% of patients and in the pelvic area in 28.3%. The overall intraoperative morbidity rate was 5.9%, while the postoperative morbidity rate was 10.4%, with only 3 patients presenting grade 3 morbidity. CONCLUSIONS: Transperitoneal para-aortic and pelvic lymphadenectomy provides precise information about nodal state and allows personalized treatment planning in patients with LACC, avoiding false negative (FN) and false positive (FP) imaging results. In 17.9% of patients, the external beam radiotherapy (EBRT) field had to include the aortic area, whilst 47.7% received pelvic boost to the involved nodes.

Image-guided brachytherapy in cervical cancer: Experience in the Complejo Hospitalario de Navarra.

PURPOSE: To evaluate dosimetric and clinical findings of MRI-guided HDR brachytherapy (HDR-B) for cervical carcinoma. MATERIAL AND METHODS: All patients had a CT, MRI and pelvic-paraaortic lymphadenectomy. Treatment: pelvic (+/-)para-aortic3D/IMRT radiotherapy (45 Gy), weekly cisplatin and HDR-B and pelvic node/parametrial boost 60 Gy until interstitial brachytherapy was done. Two implants: 2008-2011: 5 fractions of 6 Gy, 2011: 2016, 4 fractions of 7 Gy. MRI/TAC were done in each implant. The following were defined: GTV, CTH-HR, CTV-IR; OAR: rectum, bladder and sigmoid. RESULTS: From 2007 to 2016: 57 patients. Patients: T1b2-T2a: 4p, T2b 41p, T3a: 2p; T3B 8p T4a: 2p; N0: 32p, N1 21p, no lymphadenectomy: 4p. Median follow up: 74.6 m (16-122 m), recurrence: 5p local, 6p node, 9p metastasis and 37p without recurrence.Local control 5 years: 90.1%; Ib2-IIB: 94.8%, III-IVa: 72.2%. (p:0.01). RDFS 5y was 92.5%; IB2-IIB: 93%, III: 85% (p:0.024); for pN0: 100%; pN+ iliac-paraaortic: 71.4% (p: 0.007). MFS 5y was 84.1%. Overall survival (OS) at 5y: 66.6% and the cancer specific survival (CEOS) was 74%. Univariate analysis survival: stage Ib2-II 83% vs. III-IVa 41% (p = 0.001); histology: squamous 78%, adenocarcinoma 59.7% (p: ns); lymph node: N0 85% vs. PA+P- 72%, and PA+P+ 35% (p = 0.010). In relation with: HR-CTV dose > 85 Gy, CEOS: 82.5% vs. 77%, and volume CTV-HR < 30 cc: 81.8% and >30 cc: 67%; p: ns. Acute grade 2-3 toxicity: rectal 15.7%, intestinal 15.7% and vesical 15.5%. CONCLUSION: Use of interstitial HDR-BQ guided by RM increased CTV-HR dose and local control, like EMBRACE results. Nodal boost improves RDFS and perhaps OS.

Image guided brachytherapy in locally advanced cervical cancer: Improved pelvic control and survival in RetroEMBRACE, a multicenter cohort study.

PURPOSE: Image guided brachytherapy (IGBT) for locally advanced cervical cancer allows dose escalation to the high-risk clinical target volume (HRCTV) while sparing organs at risk (OAR). This is the first comprehensive report on clinical outcome in a large multi-institutional cohort. PATIENTS AND METHODS: From twelve centres 731 patients, treated with definitive EBRT±concurrent chemotherapy followed by IGBT, were analysed. Kaplan-Meier estimates at 3/5years were calculated for local control (LC, primary endpoint), pelvic control (PC), overall survival (OS), cancer specific survival (CSS). In 610 patients, G3-4 late toxicity (CTCAEv3.0) was reported. RESULTS: Median follow up was 43months, percent of patients per FIGO stage IA/IB/IIA 22.8%, IIB 50.4%, IIIA-IVB 26.8%. 84.8% had squamous cell carcinomas; 40.5% lymph node involvement. Mean EBRT dose was 46±2.5Gy; 77.4% received concurrent chemotherapy. Mean D90 HRCTV was 87±15Gy (EQD210), mean D2cc was: bladder 81±22Gy, rectum 64±9Gy, sigmoid 66±10Gy and bowel 64±9Gy (all EQD23). The 3/5-year actuarial LC, PC, CSS, OS were 91%/89%, 87%/84%, 79%/73%, 74%/65%. Actuarial LC at 3/5years for IB, IIB, IIIB was 98%/98%, 93%/91%, 79%/75%. Actuarial PC at 3/5years for IB, IIB, IIIB was 96%/96%, 89%/87%, 73%/67%. Actuarial 5-year G3-G5 morbidity was 5%, 7%, 5% for bladder, gastrointestinal tract, vagina. CONCLUSION: IGBT combined with radio-chemotherapy leads to excellent LC (91%), PC (87%), OS (74%), CSS (79%) with limited severe morbidity.

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

PURPOSE: To 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 MATERIALS: Fifteen 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). RESULTS: With 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%. CONCLUSIONS: HDR-ITB alone is a reasonable salvage treatment option in a significant number of patients with previously irradiated gynecologic tumors.

Long-term results of 1-week intravaginal high-dose-rate brachytherapy alone for endometrial cancer.

OBJECTIVE: To compare the biologic equivalence in terms of local control and toxicity of a short course of high-dose-rate intravaginal brachytherapy alone (IVBa) delivered over five consecutive days (25 Gy/5 Rx/5 days) to other more protracted classical schemes 21 Gy/3 Rx/14-28 days (Postoperative Radiation Therapy in Endometrial Carcinoma [PORTEC]-2/Memorial Sloan-Kettering Cancer Center). METHODS AND MATERIALS: From February 2001 to May 2008, 122 patients with International Federation of Gynecology and Obstetrics Stage IaG3-IIIaG2 endometrial adenocarcinoma were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by postoperative IVBa. Seventy-seven patients (63.1%) underwent surgical staging. Total IVBa dose was 25Gy in five consecutive daily fractions prescribed at 0.5-cm depth. RESULTS: After a median followup of 4.1 years, the rates of Radiation Therapy Oncology Group Grades 1, 2, and ≥3 complications were 12.9%, 3.4%, and 0.8%, respectively. Five patients (4.1%) presented locoregional failures: two isolated nodal pelvic failures, one vaginal pelvic relapse (intra-abdominal lymph node metastases), one vaginal distant failure, and one combined locoregional and distant failure. The 8.5-year actuarial vaginal control rate was 97.5%, and the pelvic control rate was 94.3%. Six other patients developed distant metastases alone. The 8.5-year actuarial overall and disease-free survival rates were 90.3% and 87.2%, respectively. Univariate analysis revealed that histologic grade, deep myometrial invasion, advanced age, and categorization as high intermediate-risk patient according to the PORTEC-2 and the Gynecologic Oncology Group (GOG)-99 stratifications were statistically significant prognostic factors. After multivariate analysis, histologic grade (p=0.001) and high intermediate risk according to GOG-99 (p=0.004) and PORTEC-2 (p=0.001) remained significant. CONCLUSIONS: The proposed scheme reproduces the excellent results obtained with more protracted schemes and has the added advantage of shortened overall treatment time.

Impact of radiotherapy on the quality of life of elderly patients with localized breast cancer. A prospective study.

INTRODUCTION: There are few studies on the effect on quality of life (QL) of cancer-related illness and treatment in elderly patients. The aim of this work was to evaluate prospectively QL in a sample of elderly patients with stages I.III breast cancer who started radiotherapy treatment and compare their QL with that of a sample of younger patients. MATERIALS AND METHODS: Forty-eight patients, > or = 65 years of age completed the European Organization for Research and Treatment of Cancer (EORTC) QL questionnaires QLQ-C30 and QLQ-BR23, and the Interview for Deterioration in Daily Living Activities in Dementia (IDDD) daily activities scale three times throughout treatment and follow-up periods. Clinical and demographic data were also recorded. Fifty patients ages 40-64 years with the same disease stage and treatment modality had previously completed the QL questionnaires. QL scores, changes in them among the three assessments, differences between groups based on clinical factors, and differences between the two samples were calculated. RESULTS: QL scoring was good and stable (>70/100 points) in most areas, in line with clinical data. Light and moderate limitations occurred in global QL and some emotional, sexual, and treatment-related areas. Moderate decreases (10-20) appeared in some toxicity-related areas, which recovered during the follow-up period. Breast-conservation and sentinel-node patients presented higher scores in emotional areas. There were few QL differences among agebased samples. CONCLUSIONS: QL and clinical data indicate radiotherapy was well tolerated. Age should not be the only factor evaluated when deciding upon treatment for breast cancer patients.

Intravaginal 1-week high-dose-rate brachytherapy alone for Stages I-II endometrial cancer.

OBJECTIVE: To evaluate the feasibility and intermediate-term results of a short course of high-dose-rate (HDR) intravaginal brachytherapy only after hysterectomy. METHODS AND MATERIALS: From December 1999 to February 2005, 50 patients with International federation of gynecology and obstetrics Stages IA-IIB endometrioid endometrial adenocarcinoma were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by postoperative HDR brachytherapy alone. The mean age of the patients was 62.6 years (range 42-86). International federation of gynecology and obstetrics patient grouping included IaG3N(x) (n=1), IbG1N(0) (n=1), IbG1N(x) (n=2), IbG2N(0) (n=10), IbG2N(x) (n=20), IbG3N(0) (n=3), IbG3N(x) (n=1), IcG1N(x) (n=2), IcG2N(0) (n=3), IcG3N(0) (n=3), IIaG1N(x) (n=2), IIaG2N(x) (n=1), and IIbG1N(0) (n=1). Twenty-one patients (42.0%) had been surgically staged. Four to 16 weeks after surgery (median 42d, range 28-112), all patients received HDR intravaginal brachytherapy to 25Gy in five consecutive 5-Gy daily fractions prescribed at 0.5-cm depth. Median HDR brachytherapy treatment duration was 5 days (range 5-12). RESULTS: After a median followup of 37 months (range 12-80), the overall survival and disease-free survival were 96%. No vaginal or pelvic recurrences have been observed. One patient (2%) developed distant metastases. No late toxicities of Grade 3 or greater have been reported. CONCLUSIONS: The results reported in this study are in agreement with previous reports of postoperative HDR brachytherapy alone in early-stage endometrial cancer. HDR brachytherapy alone seems to provide adequate tumor control. The fractionation schedule proposed (25Gy in five consecutive daily treatments) was well tolerated and is convenient for patients living far from the radiation center.

Perioperative high-dose-rate brachytherapy in locally advanced and recurrent gynecologic cancer: Initial results of a phase II trial.

BACKGROUND: This study was undertaken to determine the feasibility of perioperative high-dose-rate brachytherapy (PHDRB) as an adjunct to salvage surgery in primary advanced or recurrent gynecologic cancer. METHODS: Twenty-five patients with either locally advanced (n = 4) or recurrent (n = 21) gynecologic cancer suitable for salvage surgery were included. Unirradiated patients were treated with preoperative chemoradiation followed by salvage surgery and PHDRB (R0 and R1 resections receiving 16 or 24 Gy, respectively). Previously irradiated patients were treated with salvage surgery and PHDRB alone with 32 or 40 Gy for R0 or R1 resections, respectively. RESULTS: Resections were categorized as R0 in 9 patients (36.0%) and R1 in 16 (64.0%). Four previously irradiated patients suffered fatal pelvic bleeding between 8 and 13 months after surgery and PHDRB. After a median follow-up of 20 months (3-55+), the 4-year actuarial local and pelvic controls were 88.1% and 80.8%, respectively. The 4-year distant metastases-free survival was 40.9%. Four-year actuarial overall survival was 34.0%, with a median survival of 27.1 months (95% confidence interval: 17.5-36.8). CONCLUSIONS: Local and pelvic control results are excellent for this very high-risk-disease population. PHDRB dose in previously irradiated patients has been shifted to the closest lower level due to unacceptable vascular toxicity.