Luca Tagliaferri

Effect of whole pelvic radiotherapy for patients with locally advanced prostate cancer treated with radiotherapy and long-term androgen deprivation therapy

PURPOSE To evaluate the effect of whole pelvic radiotherapy (WPRT) in prostate cancer patients treated with RT and long-term (>1 year) androgen deprivation therapy (ADT). METHODS AND MATERIALS Prostate cancer patients with high-risk features (Stage T3-T4 and/or Gleason score≥7 and/or prostate-specific antigen level≥20 ng/mL) who had undergone RT and long-term ADT were included in the present analysis. Patients with bowel inflammatory disease, colon diverticula, and colon diverticulitis were excluded from WPRT and treated with prostate-only radiotherapy (PORT). Patients were grouped according to nodal risk involvement as assessed by the Roach formula using different cutoff levels (15%, 20%, 25%, and 30%). Biochemical disease-free survival (bDFS) was analyzed in each group according to the RT type (WPRT or PORT). RESULTS A total of 358 patients treated between 1994 and 2007 were included in the analysis (46.9% with WPRT and 53.1% with PORT). The median duration of ADT was 24 months (range, 12-38). With a median follow-up of 52 months (range, 20-150), the overall 4-year bDFS rate was 90.5%. The 4-year bDFS rate was similar between the patients who had undergone WPRT or PORT (90.4% vs. 90.5%; p=NS). However, in the group of patients with the greatest nodal risk (>30%), a significant bDFS improvement was recorded for the patients who had undergone WPRT (p=.03). No differences were seen in acute toxicity among the patients treated with WPRT or PORT. The late gastrointestinal toxicity was similar in patients treated with PORT or WPRT (p=NS). CONCLUSIONS Our analysis has supported the use of WPRT in association with long-term ADT for patients with high-risk nodal involvement (>30%), although a definitive recommendation should be confirmed by a randomized trial.

Chemoradiation With Concomitant Boosts Followed by Radical Surgery in Locally Advanced Cervical Cancer: Long-term Results of the ROMA-2 Prospective Phase 2 Study

PURPOSE This prospective, phase 2 study aimed at assessing the efficacy of accelerated fractionation radiation therapy by concomitant boosts (CBs) associated with chemoradiation therapy (CRT) of the whole pelvis, in improving the rate of pathological complete response (pCR) to treatment in patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IB2-IVA locally advanced cervical cancer. METHODS AND MATERIALS Neoadjuvant CRT included conformal irradiation of the whole pelvis with a total dose of 39.6 Gy (1.8 cGy/fraction, 22 fractions), plus additional irradiation of primary tumor and parametria with 10.8 Gy administered with CBs (0.9 cGy/fraction, 12 fractions, every other day). Concomitant chemotherapy included cisplatin (20 mg/m(2), days 1-4 and 26-30 of treatment), and capecitabine (1300 mg/m(2)/daily, orally) during the first 2 and the last 2 weeks of treatment. Radical hysterectomy plus pelvic with or without aortic lymphadenectomy was performed within 6 to 8 weeks from CRT. Toxicity was recorded according to Radiation Therapy Oncology Group toxicity criteria and Chassagne grading system. Based on the Simon design, 103 cases were required, and the regimen would be considered active if >45 pCR were registered (α error = 0.05; β error = 0.1). RESULTS pCR was documented in 51 cases (50.5%), and the regimen was considered active, according to the planned statistical assumptions. At median follow-up of 36 months (range: 7-85 months), the 3-year local failure rate was 7%, whereas the 3-year disease-free and overall survival rates were 73.0% and 86.1%, respectively. Grade 3 leukopenia and neutropenia were reported in only 1 and 2 cases, respectively. Gastrointestinal toxicity was always grade 1 or 2. CONCLUSIONS Addition of CBs in the accelerated fractionation modality to the whole pelvis chemoradiation followed by radical surgery results in a high rate of pathologically assessed complete response to CRT and a very encouraging local control rate, with acceptable toxicity.

Role of comorbidities in locally advanced cervical cancer patients administered preoperative chemoradiation: Impact on outcome and treatment-related complications

AIMS The study aimed at describing the prevalence, and pattern of comorbidities, as well as their clinical role in a large series of locally advanced cervical cancer (LACC) patients triaged to preoperative chemoradiation. METHODS The Charlson index (CCI), and the ACE27 index were used to retrospectively evaluate comorbidities in 258 LACC patients: life tables were computed by the Kaplan-Meier method; multivariate analysis was performed by Coxs regression model. RESULTS A CCI score = 0 was documented in 225 patients (87.2%), while 24 patients (9.3%) had a CCI score = 1, and only 9 patients (3.5%) had a CCI score ≥ 2. An ACE27 score = 0 was documented in 170 patients (65.9%), and was 1 in 59 patients (22.8%), 2 in 24 patients (9.3%) and 3 in 5 patients (2%). There was no association between the presence of comorbidities and clinico-pathological variables with the exception of a direct association with older age. There was no difference in the distribution of comorbid cases according to the extent of hysterectomy and lymphadenectomy. DFS or OS curves did not differ in patients with or without comorbidities according to both indexes. No difference in the distribution of patients with comorbidities according to presence of complications was documented. CONCLUSIONS The role of comorbidities in the decision-making process relative to the enrollment of LACC patients into this trimodal therapeutic strategy needs to be established in specifically designed prospective trials.

Postoperative intensity-modulated radiotherapy with simultaneous integrated boost in prostate cancer: A dose-escalation trial

OBJECTIVES To determine the recommended phase II dose of postoperative accelerated intensity modulated radiotherapy (IMRT) for prostate cancer. MATERIAL AND METHODS Step and shoot IMRT with simultaneous integrated boost (SIB) was delivered in 25 fractions over 5 weeks to patients with high risk resected prostate adenocarcinoma (stage pT3-4 and/or positive surgical margins). Pelvic nodes received 45 Gy at 1.8 Gy/fraction; dose escalation was performed only to the prostate bed (planned dose escalation: 56.8 Gy at 2.27 Gy/fraction, 59.7 Gy at 2.39 Gy/fraction, 61.25 Gy at 2.45 Gy/fraction, 62.5 Gy at 2.5 Gy/fraction). Dose-limiting toxicity (DLT) was any grade ≥ 3 acute toxicity (RTOG score). RESULTS Twenty-five patients were treated: 7 patients at the 56.75 Gy dose level, 6 patients at each subsequent dose level. Pathologic stages were: pT2c: 2; pT3a: 11; pT3b: 12; pN0: 22; pN1: 3; R0: 7; R1: 18. Median follow-up time was 19 months (range: 6-36 months). No patient experienced DLT. Grade 1-2 acute rectal and urologic toxicity was common (17 and 22 patients, respectively). CONCLUSIONS The recommended dose was 62.5 Gy in 2.5 Gy/fraction. Postoperative hypofractionated IMRT SIB for prostate cancer seemed to be well tolerated and could be tested in phase II studies.

Comparison of interstitial brachytherapy and surgery as primary treatments for nasal vestibule carcinomas

Squamous cell carcinoma arising from the nasal vestibule is a rare condition accounting for about 1% of head and neck malignancies with several peculiarities concerning both staging and treatment. The aim of this study was to compare the oncological and functional results of two different treatment modalities for the primary site: surgery and brachytherapy.

SPIDER: Managing Clinical Data of Cancer Patients Treated through a Multidisciplinary Approach by a Palm Based System

Background: The complexity of modern oncology, based on multi-disciplinary management of cancer patients, results in critical amounts of data, leading to problems in managing and sharing information. Methods: Spider is a multi-user system, based on integrated palm technology, created to facilitate data recording, managing and sharing, through Intra-Internet connection. By palms or PCs, data are collected directly at the place where information is generated. Every health professional can edit, modify and display all of the patients data according to his/her operational level. A powerful engine enables Spider’s users to create series of cancer patients’ appointments linked to one another by specified time intervals and save them as “Protocols”. Applying a protocol to the patient, the system schedules a wave of appointments and alerts keeping the correlation with time intervals previously specified by specialists. XML technology is integrated with traditional RDBMS technology to build the Electronic Patient File (EPF) updated during each patient’s admission or consultation, including any new diagnostic/therapeutic events and collective decisions. The system automatically produces all clinical documents routinely in use (discharge letters, exams’ requests, etc.). Results: Spider’s different archives include 4387 patients (Prostate, n=849; Lung, n=1596; Rectum, n=1541; Head & Neck, n=291; Cervix, n=110). The EPF includes specific modules: staging, surgery, chemotherapy, hormonotherapy, radiotherapy, toxicity, pathology, follow-up and clinical summary. Spider Hospitalization displays the ward map and important details of patients occupying each single bed. Conclusions: Spider makes data capture easier and accurate. The availability of large amounts of information accelerates outcome analysis and improves cancer research.

ENT COBRA (Consortium for Brachytherapy Data Analysis): Interdisciplinary standardized data collection system for head and neck patients treated with interventional radiotherapy (brachytherapy)

Purpose Aim of the COBRA (Consortium for Brachytherapy Data Analysis) project is to create a multicenter group (consortium) and a web-based system for standardized data collection. Material and methods GEC-ESTRO (Groupe Européen de Curiethérapie – European Society for Radiotherapy & Oncology) Head and Neck (H&N) Working Group participated in the project and in the implementation of the consortium agreement, the ontology (data-set) and the necessary COBRA software services as well as the peer reviewing of the general anatomic site-specific COBRA protocol. The ontology was defined by a multicenter task-group. Results Eleven centers from 6 countries signed an agreement and the consortium approved the ontology. We identified 3 tiers for the data set: Registry (epidemiology analysis), Procedures (prediction models and DSS), and Research (radiomics). The COBRA-Storage System (C-SS) is not time-consuming as, thanks to the use of “brokers”, data can be extracted directly from the single centers storage systems through a connection with “structured query language database” (SQL-DB), Microsoft Access®, FileMaker Pro®, or Microsoft Excel®. The system is also structured to perform automatic archiving directly from the treatment planning system or afterloading machine. The architecture is based on the concept of “on-purpose data projection”. The C-SS architecture is privacy protecting because it will never make visible data that could identify an individual patient. This C-SS can also benefit from the so called “distributed learning” approaches, in which data never leave the collecting institution, while learning algorithms and proposed predictive models are commonly shared. Conclusions Setting up a consortium is a feasible and practicable tool in the creation of an international and multi-system data sharing system. COBRA C-SS seems to be well accepted by all involved parties, primarily because it does not influence the centers own data storing technologies, procedures, and habits. Furthermore, the method preserves the privacy of all patients.

Cervical cancer response to neoadjuvant chemoradiotherapy: MRI assessment compared with surgery.

Background Imaging findings of residual cervical tumor after chemoradiotherapy can closely resemble those of post-irradiation inflammation. Purpose To determine the diagnostic performance of magnetic resonance imaging (MRI) in evaluating residual disease after chemoradiotherapy in patients with locally advanced cervical carcinoma (LACC). Material and Methods Retrospective analysis of prospectively collected data from 41 patients with histopathologically proven LACC (International Federation of Gynecology and Obstetrics stage ≥IB2) who underwent MRI before and after chemoradiotherapy. At each examination, a qualitative and semi-quantitative analysis of primary tumor, including tumor volume and signal intensity were assessed on T2-weighted (T2W) images. All patients had surgery after post-chemoradiotherapy MRI. MRI and histopathologic results were compared. Results All patients showed significant difference in tumor volume and signal intensity between pre- and post-chemoradiotherapy MRI (P < 0.0001). According to pathology, 27/41 (66%) patients had true negative and 2/41 (5%) had true positive post-chemoradiotherapy MRI. Eleven out of 41 (27%) patients showed inflammation with false positive post-chemoradiotherapy MRI and 1/41 (2%) had a false negative post-chemoradiotherapy MRI. Sensitivity, specificity, accuracy, positive predictive values, and negative predictive values of post-chemoradiotherapy MRI in predicting residual disease were 69%, 71%, 71%, 15%, and 96%, respectively. Conclusion The differentiation of residual tumor from post-irradiation inflammation with early post- chemoradiotherapy MRI (within 28–60 days) is difficult with a high risk of false positive results. Combination of qualitative and semi-quantitative analysis does not improve the accuracy. Conversely, post-chemoradiotherapy MRI has a high negative predictive value with a low risk of false negative results. The role of conventional MRI combined with functional techniques should be evaluated.

MITHRA - multiparametric MR/CT image adapted brachytherapy (MR/CT-IABT) in anal canal cancer: a feasibility study

Purpose The aim of this study is to test a novel multiparametric imaging guided procedure for high-dose-rate brachytherapy in anal canal cancer, in order to evaluate the feasibility and safety. Material and methods For this analysis, we considered all consecutive patients who underwent magnetic resonance/computed tomography image adapted brachytherapy (MR/CT-IABT) treated from February 2012 to July 2014. To conduct this project, we formed a working group that established the procedure and identified the indicators and benchmarks to evaluate the feasibility and safety. We considered the procedure acceptable if 90% of the indicators were consistent with the benchmarks. Magnetic resonance imaging with contrast and diffusion weighted imaging were performed with an MRI-compatible dummy applicator in the anus to define the position of the clinical target volume disease and biological information. A pre-implantation treatment planning was created in order to get information on the optimal position of the needles. Afterwards, the patient underwent a simulation CT and the definite post-implantation treatment planning was created. Results We treated 11 patients (4 men and 7 women) with MR/CT-IABT and we performed a total of 13 procedures. The analysis of indicators for procedure evaluation showed that all indicators were in agreement with the benchmark. The dosimetric analysis resulted in a median of V200, V150, V100, V90, V85, respectively of 24.6%, 53.4%, 93.5%, 97.6%, and 98.7%. The median coverage index (CI) was 0.94, the median dose homogeneity index (DHI) was 0.43, the median dose non-uniformity ratio (DNR) resulted 0.56, the median overdose volume index (ODI) was 0.27. We observed no episodes of common severe acute toxicities. Conclusions Brachytherapy is a possible option in anal cancer radiotherapy to perform the boost to complete external beam radiotherapy (EBRT). Magnetic resonance can also have biological advantages compared to the US. Our results suggest that the multiparametric MR/CT-IABT for anal cancer is feasible and safe. This new approach paves the way to prospective comparison studies between MRI and ultrasound-guided brachytherapy (USBT) in anal canal cancer.

BRACHYTHERAPY ALONE or with NEOADJUVANT PHOTODYNAMIC THERAPY for AMELANOTIC CHOROIDAL MELANOMA: Functional Outcomes and Local Tumor Control

Purpose: To compare visual outcomes and local tumor control between two groups of patients with amelanotic choroidal melanoma treated with brachytherapy alone, or neoadjuvant photodynamic therapy before brachytherapy. Methods: Patients diagnosed with amelanotic choroidal melanoma were recruited for the study and divided into two groups: brachytherapy alone (Group A) and photodynamic therapy preceding brachytherapy (Group B). Patients of both groups were selected to be comparable. Results: Twenty-six patients with amelanotic choroidal melanoma were enrolled in the study. Within Group B, 1 month after photodynamic therapy, ultrasonography showed reduction of tumor height in 11 patients (73.4%). The mean doses of irradiation to macula and optic nerve, at baseline were 74.37 and 52.07 Gy, whereas after photodynamic therapy there was a decrease of 17.26% (P = 0.008) and 21.22% (P = 0.025), respectively. In terms of visual acuity, a mean decrease of 14 ETDRS letters and 5 ETDRS letters was observed at 24 months follow-up, in Groups A and B, respectively (P = 0.001). Conclusion: Photodynamic therapy as neoadjuvant therapy before brachytherapy reduces tumor thickness in 73.4% of cases. As a result, a decrease of radiation toxic effects on visual function could be obtained, without compromising disease control.