Long-term outcomes of spinal SBRT. Is it important to select the treatment time?

PURPOSE: SBRT (stereotactic body radiation therapy) is widely used as a curative treatment in tumoral lesions and has become a fundamental tool for the treatment of spine metastasis. In this study, we present survival and toxicity outcomes of spine SBRT after a 2-year follow-up. METHODS/PATIENTS: Data from spine SBRT treatments performed at our institution between March 2012 and February 2020 was collected. Medical records, including demographic, primary tumor, and treatment characteristics were reviewed. Patient follow-up included clinical evaluation, imaging, and blood tests. Toxicity was recorded according to CTCAE v4.0. RESULTS: We analyzed 73 consecutive spine SBRT treatments in 60 patients. 39.7% of the cases had primary breast cancer and 23.3% had prostate cancer. Most cases (87.7%) were treated with a single SBRT fraction of 16 Gy. Median follow-up was 26.1 months (range 1.7-78.6), and 1- and 2-year overall survival (OS) rates were 96.9% and 84.2%, respectively. Local control (LC) rates at 1- and 2-years were 76.3% and 70.6%, respectively. Multivariate analysis identified histology as a prognostic factor for both OS and LC. Patients who underwent spine SBRT 6 months after the spinal lesion diagnosis had LC at 2 years of 88%, vs 61.7% for those who underwent SBRT before this period. No grade III or higher toxicity was reported. The vertebral compression fracture (VCF) rate was 4.1%. CONCLUSION: Spine SBRT at our institution showed a 2-year LC of 70.6%, without G3 toxicities. Delaying SBRT at least 6 months to administer systemic treatment was related to an improvement in local control.

Improving quality of care and clinical outcomes for rectal cancer through clinical audits in a multicentre cancer care organisation.

INTRODUCTION: Colorectal cancer treatment requires a complex, multidisciplinary approach. Because of the potential variability, monitoring through clinical audits is advisable. This study assesses the effects of a quality improvement action plan in patients with locally advanced rectal cancer and treated with radiotherapy. METHODS: Comparative, multicentre study in two cohorts of 120 patients each, selected randomly from patients diagnosed with rectal cancer who had initiated radiotherapy with a curative intent. Based on the results from a baseline clinical audit in 2013, a quality improvement action plan was designed and implemented; a second audit in 2017 evaluated its impact. RESULTS: Standardised information was present on 77.5% of the magnetic resonance imaging (MRI) staging reports. Treatment strategies were similar in all three study centres. Of the patients whose treatment was interrupted, just 9.7% received a compensation dose. There was an increase in MRI re-staging from 32.5 to 61.5%, and a significant decrease in unreported circumferential resection margins following neoadjuvant therapy (ypCRM), from 34.5 to 5.6% (p <  0.001). CONCLUSIONS: The comparison between two clinical audits showed improvements in neoadjuvant radiotherapy in rectal cancer patients. Some indicators reveal areas in need of additional efforts, for example to reduce the overall treatment time.

Predictive factors for abiraterone withdrawal syndrome. / Factores predictivos del síndrome de retirada de abiraterona.

INTRODUCTION AND OBJECTIVE: Abiraterone withdrawal syndrome (AWS) is characterized by a transient decrease in the PSA after abiraterone acetate (AA) treatment discontinuation in patients diagnosed with metastatic castration-resistant prostate cancer (mCRPC). The aim of our study is to identify the possible predictive factors of AWS at diagnosis. MATERIALS AND METHODS: We performed a retrospective study of 70 patients treated with AA at the Institut Català d'Oncologia - L'Hospitalet between 2015 and 2017. RESULTS: 11 patients presented AWS. The mean age at diagnosis was 65.73 years and the mean age of presentation was 74.18 years. Patients were in the ninth treatment cycle. The median PSA was: 30.5ng/ml at diagnosis, 33.24ng/ml in the AWS, and 15.78ng/ml before starting another treatment. The median follow-up period after AWS was 8.2 months. The predictive factors of AWS would be: high PSA (p=.002), ISUP≥4 (p=.002) and stage IV at diagnosis (p<.001). Patients with a T stage present high risk, but without statistical significance. An AUC of 0.84 was obtained, with a 95% CI between 0.77 and 0.92 (p<.001). CONCLUSIONS: The incidence of AWS is not negligible, describing prolonged responses after AA withdrawal, including the possibility of increased overall survival. These results could entail new treatment schemes for mCRPC.

Treatment of patients with unresectable squamous head and neck cancer with induction chemotherapy followed by hyperfractionated radiotherapy.

PURPOSE: The contribution of induction chemotherapy (CT) followed by hyperfractionated radiotherapy (hfRT) in unresectable squamous head and neck cancer has been evaluated in a single institution as an assistencial protocol. PATIENTS AND METHODS: From March 1994 to June 2000 all consecutive patients with unresectable disease were treated with four courses of platin plus fluorouracil based CT followed by hfRT. Tumor resectability and response was assessed by a multidisciplinary committee. RESULTS: Ninety-nine patients (pts) were treated. All of them had stage IV-M0 disease: 67 T4, 88 N2-N3. Tumor location: 62 oropharynx, 22 hypopharynx, eight oral cavity and seven larynx. Tumor response at the end of treatment: 61 patients complete response, 17 partial response, two stable disease, 10 progressive disease and nine unevaluated. With a median follow-up of 70 months the 5-year loco-regional control and overall survival was 30.3% (95% CI: 21.9-38.6) and 21.6% (95% CI: 13.4-29.8), respectively. Loco-regional control and overall survival is significantly influenced by prior response to induction CT. Main grade 3-4 toxicity related to CT was stomatitis, but there were five patients with an ischemic event. Grade 3-4 acute toxicity related to hfRT: 47 stomatitis, 20 epithelitis. Chronic toxicity related to hfRT: six emergency tracheotomies due to laryngeal edema, five pneumonia and one mucous/soft-tissue necrosis. There were eight toxic related deaths. CONCLUSION: Induction CT followed by hfRT might increase the overall survival rate in unresectable disease. HfRT resulted in a high rate of acute toxicity and its use would not be warranted in those patients with no response to induction CT who had a low probability of long-term control.

Clinical Audit of the Radiotherapy Process in Rectal Cancer: Clinical Practice Guidelines and Quality Certification Do Not Avert Variability in Clinical Practice.

BACKGROUND: The therapeutic approach to cancer is complex and multidisciplinary. Radiotherapy is among the essential treatments, whether used alone or in conjunction with other therapies. This study reports a clinical audit of the radiotherapy process to assess the process of care, evaluate adherence to agreed protocols and measure the variability to improve therapeutic quality for rectal cancer. METHODS: Multicentre retrospective cohort study in a representative sample of patients diagnosed with rectal cancer in the Institut Català d'Oncologia, a comprehensive cancer centre with three different settings. We developed a set of indicators to assess the key areas of the radiotherapy process. The clinical audit consisted of a review of a random sample of 40 clinical histories for each centre. RESULTS: The demographic profile, histology and staging of patients were similar between centres. The MRI reports did not include the distance from tumour to mesorectal fascia (rCRM) in 38.3% of the cases. 96.7% of patients received the planned dose, and 57.4% received it at the planned time. Surgery followed neoadjuvant treatment in 96.7% of the patients. Among this group, postoperative CRM was recorded in 65.5% of the cases and was negative in 93.4% of these. With regard to the 34.5% (n = 40) of cases where no CRM value was stated, there were differences between the centres. Mean follow-up was 3.4 (SD 0.6) years, and overall survival at four years was 81.7%. CONCLUSIONS: The audit revealed a suboptimal degree of adherence to clinical practice guidelines. Significant variability between centres exists from a clinical perspective but especially with regard to organization and process.

Guidelines on the standards for the training of specialised health professionals dealing with breast cancer.

According to EUSOMA position paper 'The requirements of a specialist breast unit', each breast unit should have a core team made up of health professionals who have undergone specialist training in breast cancer. In this paper, on behalf of EUSOMA, authors have identified the standards of training in breast cancer, to harmonise and foster breast care training in Europe. The aim of this paper is to contribute to the increase in the level of care in a breast unit, as the input of qualified health professionals increases the quality of breast cancer patient care.

[Brachytherapy in France in 2002: results of the ESTRO-PCBE questionnaire]. / La curiethérapie en France en 2002: résultats de l'enquête PCBE de l'ESTRO.

The authors report the results of the Patterns of Care for Brachytherapy in Europe (PCBE) throughout France. Responses were obtained for 91% of the Radiation Oncology departments, which have declared using brachytherapy for 67, and gave detailed data for 49 ones. The equipments and treated tumours were recorded. LDR brachytherapy remained the most often used (53.5%), followed by HDR (28%). PDR represented 5.5% and permanent implants 11%. The authors discuss the development of new equipment, with an aggregation of the structures, and an increase of the PDR and prostate implants use.

Patterns of care for brachytherapy in Europe. Results in Spain.

INTRODUCTION: In 2003 ESTRO began a project whose primary objective, was to make a map in the European area of infrastructures in technology and personnel for brachytherapy. MATERIAL AND METHOD: A survey and a web site were elaborated. The survey was sent to the 76 Spanish Radiation Oncology departments in May 2003. RESULTS: By the end of 2003, 66 (86.8%) services had responded, 40 (71.4%) of which had brachytherapy. The services with brachytherapy treated 73.5% of the total patients, an average of 1,199 patients. The mean number of patients treated with brachytherapy by department was 135.5 and the number of applications was 265 annually. The average number of specialists was 7, 4 of them trained in brachytherapy. The average weekly work load of the radiation oncologists, physicists, and technicians was 22.6 h, 13.8 h and 21.0 h, respectively. The mean time dedicated to each patient by radiation oncologists, physicists and technicians was 9.2 h; 6.19 h; 7.2 h, respectively. The total number of afterloaders was 43 (22 HDR, 18 LDR, 3 PDR). The tumours most frequently treated with brachytherapy were gynaecological (56.24%), breast (14.2%) and prostate (11.7%). High dose rate was used in 47.46% of the patients and low dose rate in 47.24%. Between 1997 and 2002 there was an increase of 50.53% in patients treated with brachytherapy. CONCLUSIONS: The survey shows the brachytherapy resources and activity in Spain up to 2003. Increased use of brachytherapy in prostate tumours, prevalence of gynaecology brachytherapy and similar number of treatments with HDR and LDR are demonstrated in the Patterns of Care of Brachytherapy in Europe (PCBE) study in Spain.

Preliminary analysis of the resources in brachytherapy in Europe and its variability of use.

PURPOSE: The main objective of the program <> is to establish a group with detailed information on brachytherapy throughout Europe. METHODS: The data was compiled by the general coordinator, the ESTRO, and the <> through a website. RESULTS: A total of 32 countries reported data from at least 50% of their centres (criteria of inclusion). Countries were grouped in three categories based on the time of incorporation to the European Union. The majority of treatments belonged to gynaecological tumours. A large spread was found regarding workload of specialists depending on centre and group. CONCLUSION: Collection of information by a website is a feasible methodology. An increase in brachytherapy treatment was observed in all 3 groups by a rate of more than 20% (year 2002 versus year 1997). These results advocate for the continuation of the PCBE study to demonstrate the development in the field, such as an increase or decrease of patient numbers per tumour category.

Association between single-nucleotide polymorphisms in DNA double-strand break repair genes and prostate cancer aggressiveness in the Spanish population.

BACKGROUND: Novel predictors of prognosis and treatment response for prostate cancer (PCa) are required to better individualize treatment. Single-nucleotide polymorphisms (SNPs) in four genes directly (XRCC5 (X-ray repair complementing defective repair in Chinese hamster cells 5) and XRCC6 (X-ray repair complementing defective repair in Chinese hamster cells 6)) or indirectly (PARP1 and major vault protein (MVP)) involved in non-homologous end joining were examined in 494 Spanish PCa patients. METHODS: A total of 22 SNPs were genotyped in a Biotrove OpenArray NT Cycler. Clinical tumor stage, diagnostic PSA serum levels and Gleason score at diagnosis were obtained for all participants. Genotypic and allelic frequencies were determined using the web-based environment SNPator. RESULTS: (XRCC6) rs2267437 appeared as a risk factor for developing more aggressive PCa tumors. Those patients carrying the GG genotype were at higher risk of developing bigger tumors (odds ratio (OR)=2.04, 95% confidence interval (CI) 1.26-3.29, P=0.004), present higher diagnostic PSA levels (OR=2.12, 95% CI 1.19-3.78, P=0.011), higher Gleason score (OR=1.65, 95% CI 1.01-2.68, P=0.044) and D'Amico higher risk tumors (OR=2.38, 95% CI 1.24-4.58, P=0.009) than those patients carrying the CC/CG genotypes. Those patients carrying the (MVP) rs3815824 TT genotype were at higher risk of presenting higher diagnostic PSA levels (OR=4.74, 95% CI 1.40-16.07, P=0.013) than those patients carrying the CC genotype. When both SNPs were analyzed in combination, those patients carrying the risk genotypes were at higher risk of developing D'Amico higher risk tumors (OR=3.33, 95% CI 1.56-7.17, P=0.002). CONCLUSIONS: We believe that for the first time, genetic variants at XRCC6 and MVP genes are associated with risk of more aggressive disease, and would be taken into account when assessing the malignancy of PCa.

High dose level radiation therapy for local tumour control in esthesioneuroblastoma.

Esthesioneuroblastoma is an uncommon tumour of neural crest origin arising in the nasal cavity. This paper is a retrospective review of 7 patients with esthesioneuroblastoma treated at a single institution from May 1974 to July 1990. 5 patients were treated with radiation therapy alone and 2 patients were irradiated after surgical resection. No local or regional occurrence was observed in any patient at 6 months, or at 1, 3, 6, 11.5 and 12 years following treatment. One patient died of intercurrent disease 6 years after radiation therapy. 2 patients died of disease, 1 of distant metastasis at 6 months and the other patient of meningeal carcinomatosis and distant metastases 1 year after treatment. One patient is alive with distant metastases 1 year after treatment. None of the patients experienced significant complications of irradiation. High-dose irradiation (60 Gy or more) alone or in combination with resection is an effective local treatment modality for esthesioneuroblastoma.

The role of radiation therapy in inverted papilloma of the nasal cavity and paranasal sinuses.

Between December 1969 and March 1985, seven patients with advanced biologically aggressive inverted or cylindrical cell papillomas were treated with irradiation at the University of Florida. Three patients were treated with radiation therapy alone, and four patients were irradiated either before (one patient) or after (three patients) resection. No recurrences were observed in six patients at 4.5, 7, 8, 8, 9, and 20 years following treatment (including two who died of intercurrent disease at 7 and 9 years after radiation therapy without evidence of recurrent tumor). One patient treated with irradiation alone for an advanced recurrent papilloma developed a local recurrence extending into the frontal lobe of the brain and died 17 months after radiation therapy. None of the patients experienced a significant complication of irradiation. Although surgery is generally the primary treatment modality for this disease, radiation therapy should be considered for patients with advanced, incompletely resected, or unresectable lesions.

Cytogenetic effects of radiotherapy: frequency and types of chromosome aberrations.

The frequency and types of chromosome aberrations induced by ionizing radiation in cancer patients were evaluated in 24 cases studied just before and immediately after radiotherapy. The incidence of aberrant metaphases prior to treatment was 9.98% and increased significantly after treatment to 32.8%. The frequency of chromosome aberrations before radiotherapy was, with the exception of the cases of breast cancer and seminoma, significantly higher than that in our laboratory controls. A comparison of chromosome abnormalities observed before and after treatment indicated that dicentric translocations, rings, and reciprocal translocations increased by a factor of 23, 13, and 11, respectively, after radiotherapy. Ionizing radiation produces more asymmetrical than symmetrical chromosome aberrations and more two-break than one-break anomalies.

External beam irradiation plus (192)Ir implant after breast-preserving surgery in women with early breast cancer.

PURPOSE: To provide more information for the clinician and to analyze the impact of the boost with brachytherapy on the local disease-free survival (LDFS), disease-free survival (DFS), specific overall survival (OS), and cosmesis, a retrospective study of external radiation therapy and (192)Ir implantation in early breast cancer at Institut Català d'Oncologia has been undertaken. PATIENTS AND METHODS: From 1986 to 1996, 530 patients were selected for this study with a median follow-up period of 39.5 months (range, 10-115 months). External radiation therapy (combined with brachytherapy) was administered postoperatively to the breast in all patients. Mean given dose was 48.7 Gy (range, 42-52 Gy) with external radiation therapy to the breast, and 16.8 Gy (range, 10-27 Gy) was the mean dose with brachytherapy. Variables have been tested for cosmesis. Univariate and multivariate analysis have also been carried out. RESULTS: Mean age of the patients was 54 years (range, 28-81 years). Stages were distributed as follows: 350 patients (66%) in Stage I, 173 in Stage II (32.8%), and 7 in Stage III (1.1%). Pathologic distribution was 445 patients with infiltrating ductal carcinoma (84%), 20 patients with infiltrating lobular carcinoma (4%), and 65 patients (12%) of a miscellaneous group. OS for the entire group was 89.4% and 85.9% at 5 and 7 years respectively. Probability of DFS was 81.7% and 70.1% at 5 and 7 years. The LDFS was 94.9% and 91.7% at 5 and 7 years. The MFS probability was 85.5% and 76.9% at 5 and 7 years, respectively. Univariate analysis demonstrated that age (older than 52 years), premenopausal status, moderate and high histologic grades (Grades II-III), and presence of intraductal comedocarcinoma were prognostic factors for local relapse. Multivariate analysis for local disease-free survival demonstrated that only perineural or muscular infiltration remain as prognostic factors. Tumor dose bed of 70 Gy or higher had a negative impact in breast subcutaneous fibrosis, whereas dose rate lower than 65 cGy/h was better for skin color at 2 years. CONCLUSION: We conclude that patients with early-stage breast cancer undergoing external radiotherapy and LDR brachytherapy can be effectively managed. Overall survival, long-term local control, and cosmetic control are excellent.

Primary subglottic cancer: results of radical radiation therapy.

Between October 1964 and December 1985, six patients with primary squamous cell carcinoma of the subglottis were treated with radical radiation therapy at the University of Florida. The disease was staged as Tis (one patient), T2N0 (two patients), and T4N0 (three patients). Local control was achieved with irradiation in four patients (66%) who were observed for 3.5, 4, 4, and 5 years after radiation therapy. Two patients whose tumors recurred at the primary site underwent salvage laryngectomy, which was successful in one patient.

Impact of radiotherapy on local control and survival in uterine sarcomas: a retrospective study from the Grup Oncologic Català-Occità.

PURPOSE: In order to provide more information for the clinician and to analyze the impact of radiation therapy on the loco-regional disease-free interval (LRFI), disease-free interval (DFI) and specific overall survival (OS), a multicentric retrospective study of uterine sarcomas has been undertaken using cases reported to the Grup Oncològic Català-Occità (GOCO). PATIENTS AND METHODS: One hundred three patients were selected for this study with a median follow-up period of 49 months. Patients were restaged using the FIGO classification for endometrial adenocarcinoma. Radiotherapy was administered postoperatively to the entire pelvis in 52% of cases (54/103) and was combined with brachytherapy in 24 patients. Mean given dose was 48 Gy, with a 95% confidence interval of 45 to 50 Gy. Variables have been tested for homogeneity between hospitals. Univariate and multivariate analyses have also been carried out. RESULTS: Mean age of the selected patients was 59 years (range 35-84). Stages were distributed as follows: 66 patients (64%) in Stage I; 16 in Stage II (15.5%); 12 in Stage III (11.5%); 9 patients in Stage IVa (9%). Pathological distribution was 41.5% leiomyosarcoma, 39% mixed Mullerian tumours, 16.5% stromal sarcomas, and 2.9% of a miscellaneous group. Overall survival for the entire group was 63.7% and 56% at 2 and 5 years, respectively. Probability of LRFI reached 59.8% at 2 years and 57.4 at 5 years. The DFI at 2 and 5 years were 52.9 % and 48.7%, respectively. The LRFI probability was 41% and 36% at 2 and 5 years, respectively, without radiotherapy and reached 76% at 2 and 5 years among those patients treated with radiotherapy. There was also an increase in DFI probability because of the effect of radiotherapy, from 35% to 68.5% and from 33% to 53% at 2 and 5 years, respectively. The overall survival probability for patients treated with radiotherapy was 76% and 73% at 2 and 5 years, respectively and 51% at 2 years and 37% at 5 years without radiotherapy. Multivariate analysis demonstrated that radiotherapy improved LRFI, DFI, and overall survival. CONCLUSION: We conclude that postoperative radiotherapy in our series of patients diagnosed with uterine sarcoma has an impact on loco-regional and disease-free progression intervals and survival.

Salvage irradiation of oral and oropharyngeal cancers using interstitial radiotherapy with au-198 grains.

Fourteen patients with recurrent or persistent carcinoma of the oral cavity or oropharynx were treated with Au-198 grain implants at the Santa Creu i Sant Pau Hospital from June 1987 through April 1991. Five patients presented recurrent carcinoma, four patients persistent carcinoma, and five patients a second primary. Local control was achieved with Au-198 implants in six patients (42.8%) at 8, 16, 23, 29, 39 and 53 months following treatment. Seven patients died of local recurrence or persistent disease at 5, 7, 7, 10, 10, 12 and 15 months after interstitial implant. Three patients (21.4%) died of significant complications of salvage irradiation (Hemorrhage in two patients and edema in one patient) at 0.5, 8 and 16 months following treatment. Three patients of fourteen (21.4%) are alive and well at 53, 39 and 23 months after salvage Au-198 grain implant. Considerations regarding the usefulness of Au-198 grain implants in the treatment of recurrent or persistent oral and oropharyngeal cancer are discussed.