To assess the physics contributions and clinical outcome with three-dimensional magnetic resonance imaging-guided pulsed-dose-rate (PDR) intracavitary brachytherapy in cervical cancer patients.
The ...data from 45 patients with primary locally advanced cervical carcinoma were analyzed. The median tumor cervical volume was 64.0 cm(3) (range, 3-178). Of the 45 patients, 24 (53%) had histologic and/or radiologic pelvic involvement. After pelvic with or without para-aortic concomitant chemoradiotherapy, a PDR brachytherapy boost was delivered to a three-dimensional magnetic resonance imaging-based clinical target volume, taking into account the dose-volume constraints for critical organs and optimization of the target volume coverage.
At a median follow-up of 26 months (range, 9-47), the 2-year overall survival and disease-free survival rate was 78% and 73%, respectively. At the last follow-up visit, the disease of all patients remained locally controlled. Adding external beam radiotherapy and PDR using the equivalent dose in 2-Gy fractions model, the median dose received by 100% and 90% of the target was 54.4 Gy(alpha/beta10) and 63.5 Gy(alpha/beta10) for the intermediate-risk clinical target volume and 61.6 Gy(alpha/beta10) and 74.9 Gy(alpha/beta10) for the high-risk clinical target volume, respectively. Of the 45 patients, 23 and 2 developed acute Grade 1-2 and Grade 3 complications, respectively; 21 patients presented with delayed Grade 1-2 complications. One other patient presented with Grade 3 vesicovaginal fistula. No Grade 4 or greater complications, whether acute or delayed, were observed.
Magnetic resonance imaging-guided PDR brachytherapy with optimization integrating the limits of tolerance to critical organs allows for excellent local control rates. Moreover, the present results have confirmed that the ability to optimize dwell times can contribute to an improvement in local control rates with a low level of late side effects.
Radiotherapy with concurrent 5-fluorouracil/mitomycin-C based chemotherapy has been established as definitive standard therapy approach for anal cancer. Intensity Modulated Radiotherapy (IMRT) leads ...to a precise treatment of the tumor, allowing dose escalation on Gross Tumor Volume (GTV), with a surrounding healthy tissues sparing. Our study assessed the impact of 18-Fluorodeoxyglucose positron emission tomography (18FDG-PET/CT) on the radiotherapy contouring process and its contribution to lymphatic spread detection, resulting to a personalization of Clinical Target Volume (CTV) and dose prescription.
Thirty-seven patients, with histologically proven squamous cell carcinoma of the anal canal (SCCAC) were analyzed. All patients were evaluated with history and physical examination, trans-anal endoscopic ultrasound, pelvis magnetic resonance imaging (MRI), computed tomography (CT) scans of the chest, abdomen and pelvis and planning 18FDG-PET/CT. The GTV and CTV were drawn on CT, MRI and 18FDG-PET/CT fused images.
Thirty-four (91%) out of 37 patients presented lymph nodes involvement, in one or more areas, detected on 18FDG-PET/CT and/or MRI. The 18FDG-PET/CT showed positive lymph nodes not detected on MRI imaging (PET+, MRI-) in 14/37 patients (38%). In 14 cases, 18FDG-PET/CT allowed to a dose escalation in the involved nodes. The 18FDG-PET/CT fused images led to change the stage in 5/37(14%) cases: four cases from N0 to N1 (inguinal lymph nodes) and in one case from M0 to M1 (common iliac lymph nodes).
The 18FDG-PET/CT has a potentially relevant impact in staging and target volume delineation/definition in patients affected by anal cancer. In our experience, clinical stage variation occurred in 14% of cases. More investigations are needed to define the role of 18FDG-PET/CT in the target volume delineation of anal cancer.
: Exclusive radiotherapy, including external beam radiotherapy (EBRT) and interventional radiotherapy/brachytherapy (IRT/BT), with concurrent cisplatin-based chemotherapy, represents the standard of ...care in patients with locally advanced cervical cancer (LACC). The emerging topic of vaginal toxicity has become a key endpoint in LACC management, although different approaches and non-standardized procedures were available. Our aim was to analyze a nationwide study of the attitudes of Italian gynecological radiation oncology teams in the management of LACC patients' vaginal toxicities.
: A nationwide survey of radiation oncologists specializing in the treatment of gynecological malignancies was performed, using the free SurveyMonkey platform, consisting of 26 items. The questionnaire was proposed by the Italian Association of Radiation Oncologists (AIRO) gynecological working group to all 183 Italian radiation oncology institutions, as per AIRO's website. Results: Fifty-eight questionnaires (31%) were completed and returned. The assessment of acute and late vaginal toxicities was systematic in 32 (55.2%) and 26 (44.8%) centers, respectively. In the case of EBRT, 70.7% of centers, according to the contouring and treatment plan data, did not contour the vagina as an organ at risk (OAR). Vaginal dose constraints were heterogeneous for both EBRT and IRT/BT. Local treatment to prevent vaginal toxicity was prescribed by 60.3% of radiation oncologists, mostly vaginal hyaluronic acid cream, and one center recommended vaginal estrogen preparations. During follow-up visits, vaginal toxicity was considered an issue to be investigated always (
= 31) or in sexually active women only (
= 11).
: This survey showed that wide variation exists with regard to recording and treating vaginal toxicity after exclusive chemoradiation for cervical cancer, underscoring the need to develop more comprehensive guidelines for contouring e-dose reporting of the vagina, so as to implement clinical approaches for vaginal toxicity.
To evaluate the reliability of algebraic sum with respect to rigid fusion of treatment plans related to adjuvant external beam pelvic radiotherapy (APR) and vaginal cuff high-dose-rate brachytherapy ...(BT) in uterine cancer patients.
For algebraic sum, APR and BT doses were mathematically added. Rigid fusion was realized overlapping computed tomography (CT) images of APR and BT treatment plans. Rectum and bladder were considered reference organs at risk (OARs). Following dose (D) parameters were examined: D
(0.5 cc), D
and D
for rectum, D
(0.5 cc) and D
for bladder; for each parameter, differences between the two adopted methods were reported as Δ-values.
Twenty uterine cancer patients submitted to radical surgery followed by APR plus vaginal cuff BT were reviewed. APR was done with a dose of 25 × 2 Gy. All patients also receveid a vaginal cuff boost with BT at the dose of 2 × 5 Gy. Differences between mean cumulative doses calculated with rigid fusion and algebraic sum were evaluated. For the rectum and bladder ΔD
, there were no significant differences, and BT contribution resulted minimal. An apparent significant difference value was registered in bladder ΔD
(0.5 cc). No toxicity was observed.
In uterine cancer patients submitted to APR and vaginal cuff BT, algebraic sum and rigid plan fusion of doses allowed to obtain similar results in evaluating cumulative OARs' doses. Further investigations and increased number of patients are recommended to confirm our findings.
Summary Introduction Positron emission tomography (PET) with F18 Flurodeoxyglucose (FDG) has been evaluated and found to be a useful diagnostic tool in a certain number of malignancies, particularly ...in providing crucial assessment of metabolic activity of the tumour. We herein review and discuss the place and role of FDG–PET scan in cervix carcinoma patients’ management. Materials and methods Data for this review were identified by searches of Medline with and without MeSH database and Cancerlit. Studies were selected only if they were randomised clinical trials or historical reports. References were also identified from reference lists in relevant preciously published articles. Recent guidelines and meta-analyses were included. Only published articles were taken into consideration. Results Although FDG–PET may be useful in the primary cervical tumours morphologic and metabolic evaluation, it seems to have limited place for disease staging in patients with early-stage disease (less than 4 cm). Hybrid PET/CT is an effective imaging technique in the lymph node staging of locally advanced cervix carcinoma with negative CT findings and may lead to substantial changes in treatment planning for several patients. FDG–PET provides meaningful information for the early evaluation of therapeutic response and long-term follow-up. Conclusion Several reports have demonstrated the efficacy of FDG–PET in both pre-treatment staging and post-treatment evaluation of patients with cervical carcinoma. Further evaluation in prospective clinical trials will be required to assess the clinical benefit of this strategy.
Serous adenocarcinoma (uterine serous carcinoma - USC) is a rare and aggressive histologic subtype of endometrial cancer, with a high-rate of recurrence and poor prognosis. The adjuvant treatment for ...stage I patients is unclear. The purpose of this study was to evaluate the outcomes of stage I USC treated exclusively with chemotherapy plus vaginal brachytherapy (VBT).
A systematic research using PubMed, Scopus, and Cochrane library was conducted to identify full articles evaluating the efficacy of VBT in patients with stage I USC. A search in ClinicalTrials.gov was performed in order to detect ongoing or recently completed trials, and in PROSPERO for searching ongoing or recently completed systematic reviews.
All studies were retrospective and 364 of evaluated patients were found. The average local control was 97.5% (range, 91-100%), the disease free-survival was 88% (range, 82-94%), the overall survival was 93% (range, 72-100%), the specific cancer survival was 89.4% (range, 84.8-94%), and the G3-G4 toxicity was 0-8%.
These data support the concept that in adequately selected patients, VBT alone may be a suitable radiotherapy technique in women with stage I USC who underwent surgical staging and received adjuvant chemotherapy.
This systematic review focused on rare histological types of corpus uteri malignancy, including uterine carcinosarcoma (UCS), uterine clear cell carcinoma (UCCC), and uterine papillary serous ...carcinoma (UPSC), and it is proposed to assist with clinical decision-making. Adjuvant treatment decisions must be made based on available evidences. We mainly investigated the role of vaginal interventional radiotherapy (VIRt) in UCS, UCCC, and UPSC managements.
A systematic research using PubMed and Cochrane library was conducted to identify full articles evaluating the efficacy of VIRt in early-stage UPSC, UCCC, and UCS. A search in ClinicalTrials.gov was performed in order to detect ongoing or recently completed trials as well as in PROSPERO for ongoing or recently completed systematic reviews. Survival outcomes and toxicity rates were obtained.
All studies were retrospective. For UCS, the number of evaluated patients was 432. The 2- to 5-year average local control (LC) was 91% (range, 74.2-96%), disease-free survival (DFS) 88% (range, 82-94%), overall survival (OS) 79% (range, 53.8-84.3%), the average 5-year cancer-specific survival (CSS) was 70% (range, 70-94%), and G3-G4 toxicity was 0%. For UCCC, the number of investigated patients was 335 (UCCC - 124, mixed - 211), with an average 5-year LC of 100%, DFS of 83% (range, 82-90%), OS of 93% (range, 83-100%), and G3-G4 toxicity of 0%. For UPSC, the number of examined patients was 1,092 (UPSC - 866, mixed - 226). The average 5-year LC was 97% (range, 87.1-100%), DFS 84% (range, 74.7-95.6%), OS 93% (range, 71.9-100%), CSS 89% (range, 78.9-94%), and G3-G4 toxicity was 0%.
These data suggest that in adequately selected early-stage UPSC and UCCC patients, VIRt alone may be suitable in women who underwent surgical staging and received adjuvant chemotherapy. In early-stage UCS, a multidisciplinary therapeutic approach has to be planned, considering high-rate of pelvic and distant relapses.
Background
Recent studies have reported improvement of outcomes (progression‐free survival, overall survival, and prolongation of androgen deprivation treatment‐free survival) with stereotactic body ...radiotherapy (SBRT) in non‐small cell lung cancer and prostate cancer. The aim of this retrospective, multicenter study (MITO RT‐01) was to define activity and safety of SBRT in a very large, real‐world data set of patients with metastatic, persistent, and recurrent ovarian cancer (MPR‐OC).
Materials and Methods
The endpoints of the study were the rate of complete response (CR) to SBRT and the 24‐month actuarial local control (LC) rate on “per‐lesion” basis. The secondary endpoints were acute and late toxicities and the 24‐month actuarial late toxicity‐free survival. Objective response rate (ORR) included CR and partial response (PR). Clinical benefit (CB) included ORR and stable disease (SD). Toxicity was evaluated by the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) and Common Terminology Criteria for Adverse Events (CTCAE) scales, according to center policy. Logistic and Cox regression were used for the uni‐ and multivariate analysis of factors predicting clinical CR and actuarial outcomes.
Results
CR, PR, and SD were observed in 291 (65.2%), 106 (23.8%), and 33 (7.4%) lesions, giving a rate of CB of 96.4%. Patient aged ≤60 years, planning target volume (PTV) ≤18 cm3, lymph node disease, and biologically effective dose α/β10 > 70 Gy were associated with higher chance of CR in the multivariate analysis. With a median follow‐up of 22 months (range, 3–120), the 24‐month actuarial LC rate was 81.9%. Achievement of CR and total dose >25 Gy were associated with better LC rate in the multivariate analysis. Mild toxicity was experienced in 54 (20.7%) patients; of 63 side effects, 48 were grade 1, and 15 were grade 2. The 24‐month late toxicity‐free survival rate was 95.1%.
Conclusions
This study confirms the activity and safety of SBRT in patients with MPR‐OC and identifies clinical and treatment parameters able to predict CR and LC rate.
Implications for Practice
This study aimed to define activity and safety of stereotactic body radiotherapy (SBRT) in a very large, real life data set of patients with metastatic, persistent, recurrent ovarian cancer (MPR‐OC). Patient age <60 years, PTV <18 cm3, lymph node disease, and biologically effective dose α/β10 >70 Gy were associated with higher chance of complete response (CR). Achievement of CR and total dose >25 Gy were associated with better local control (LC) rate. Mild toxicity was experienced in 20.7% of patients. In conclusion, this study confirms the activity and safety of SBRT in MPR‐OC patients and identifies clinical and treatment parameters able to predict CR and LC rate.
Traditional management of recurrent ovarian cancer is system chemotherapy. This article considers an alternative, focusing on the activity and safety of stereotactic body radiotherapy for patients with ovarian cancer.
We present a large real-world multicentric dataset of ovarian, uterine and cervical oligometastatic lesions treated with SBRT exploring efficacy and clinical outcomes. In addition, an exploratory ...machine learning analysis was performed.
A pooled analysis of gynecological oligometastases in terms of efficacy and clinical outcomes as well an exploratory machine learning model to predict the CR to SBRT were carried out. The CR rate following radiotherapy (RT) was the study main endpoint. The secondary endpoints included the 2-year actuarial LC, DMFS, PFS, and OS.
501 patients from 21 radiation oncology institutions with 846 gynecological metastases were analyzed, mainly ovarian (53.1%) and uterine metastases(32.1%).Multiple fraction radiotherapy was used in 762 metastases(90.1%).The most frequent schedule was 24 Gy in 3 fractions(13.4%). CR was observed in 538(63.7%) lesions. The Machine learning analysis showed a poor ability to find covariates strong enough to predict CR in the whole series. Analyzing them separately, in uterine cancer, if RT dose≥78.3Gy, the CR probability was 75.4%; if volume was <13.7 cc, the CR probability became 85.1%. In ovarian cancer, if the lesion was a lymph node, the CR probability was 71.4%; if volume was <17 cc, the CR probability rose to 78.4%. No covariate predicted the CR for cervical lesions. The overall 2-year actuarial LC was 79.2%, however it was 91.5% for CR and 52.5% for not CR lesions(p < 0.001). The overall 2-year DMFS, PFS and OS rate were 27.3%, 24.8% and 71.0%, with significant differences between CR and not CR.
CR was substantially associated to patient outcomes in our series of gynecological cancer oligometastatic lesions. The ability to predict a CR through artificial intelligence could also drive treatment choices in the context of personalized oncology.
•A large series of 846 oligometastatic gynecological cancers from 21 Institutions underwent Stereotactic Radiotherapy.•Excellent objective response and local control rates were reported in the whole series.•An Artificial Intelligence model (Machine learning analysis) was performed to find variables predicting complete response.•High dose, small target volume, and type of lesion were able to predict complete response in uterine and ovarian cancers.