A patterns of care analysis of hyperthermia in combination with radio(chemo)therapy or chemotherapy in European clinical centers.

PURPOSE: The combination of hyperthermia (HT) with radio(chemo)therapy or chemotherapy (CT) is an established treatment strategy for specific indications. Its application in routine clinical practice in Europe depends on regulatory and local conditions. We conducted a survey among European clinical centers to determine current practice of HT. METHODS: A questionnaire with 22 questions was sent to 24 European HT centers. The questions were divided into two main categories. The first category assessed how many patients are treated with HT in combination with radio(chemo)therapy or CT for specific indications per year. The second category addressed which hyperthermia parameters are recorded. Analysis was performed using descriptive methods. RESULTS: The response rate was 71% (17/24) and 16 centers were included in this evaluation. Annually, these 16 centers treat approximately 637 patients using HT in combination with radio(chemo)therapy or CT. On average, 34% (range: 3-100%) of patients are treated in clinical study protocols. Temperature readings and the time interval between HT and radio(chemo)therapy or CT are recorded in 13 (81%) and 9 (56%) centers, respectively. The thermal dose quality parameter "cumulative equivalent minutes at 43 °C" (CEM43°C) is only evaluated in five (31%) centers for each HT session. With regard to treatment sequence, 8 (50%) centers administer HT before radio(chemo)therapy and the other 8 in the reverse order. CONCLUSION: There is a significant heterogeneity among European HT centers as to the indications treated and the recording of thermometric parameters. More evidence from clinical studies is necessary to achieve standardization of HT practice.

Deep inspiration breath hold in post-operative radiotherapy for right breast cancer: a retrospective analysis.

Background: The aim of our study is to determine whether deep inspiration breath hold (DIBH) is effective for reducing exposure of the heart, left coronary artery (LAD) and both lungs in right breast radiotherapy. Materials and methods: We have analyzed 10 consecutive patients with right-sided breast cancer (BC), simulated during free breathing (FB) and in DIBH modality. For all patients we contoured breast PTV and organs at risk (right and left lungs, heart, LAD) on both CT scans (FB and DIBH). Finally, 5 patients were treated with IMRT and 5 with VMAT techniques. Results: All patients were able to end the treatments in DIBH modalities regardless of the longer treatment time in comparison to FB. The maximum and mean dose to the heart are lower in the DIBH modality. The mean values of the heart mean dose were 1.76 Gy in DIBH and 2.19 Gy in FB. The mean heart maximum dose in DIBH and FB were, respectively, 9.3 Gy and 11 Gy. Likewise, the maximum dose to the LAD is lower in DIBH; 2.57 Gy versus 3.56 Gy in FB. Noteworthy, 3 patients with hepatomegaly treated with the DIBH technique showed a higher ipsilateral lung dose than FB, but a decrease of liver dose. Conclusion: We report that the use of DIBH for right-sided BC allows the dose to the heart, LAD and to the liver to be reduced in case of hepatomegaly. This technique is well tolerated by patients, when adequately trained, and could be considered effective even in right sided BC.

Prognostic role of pre-treatment magnetic resonance imaging (MRI)-based radiomic analysis in effectively cured head and neck squamous cell carcinoma (HNSCC) patients.

OBJECTIVES: To identify and validate baseline magnetic resonance imaging (b-MRI) radiomic features (RFs) as predictors of disease outcomes in effectively cured head and neck squamous cell carcinoma (HNSCC) patients. MATERIALS AND METHODS: Training set (TS) and validation set (VS) were retrieved from preexisting datasets (HETeCo and BD2Decide trials, respectively). Only patients with both pre- and post-contrast enhancement T1 and T2-weighted b-MRI and at least 2 years of follow-up (FUP) were selected. The combination of the best extracted RFs was used to classify low risk (LR) vs. high risk (HR) of disease recurrence. Sensitivity, specificity, and area under the curve (AUC) of the radiomic model were computed on both TS and VS. Overall survival (OS) and 5-year disease-free survival (DFS) Kaplan-Meier (KM) curves were compared for LR vs. HR. The radiomic-based risk class was used in a multivariate Cox model, including well-established clinical prognostic factors (TNM, sub-site, human papillomavirus [HPV]). RESULTS: In total, 57 patients of TS and 137 of VS were included. Three RFs were selected for the signature. Sensitivity of recurrence risk classifier was 0.82 and 0.77, specificity 0.78 and 0.81, AUC 0.83 and 0.78 for TS and VS, respectively. VS KM curves for LR vs. HR groups significantly differed both for 5-year DFS (p<.0001) and OS (p=.0004). A combined model of RFs plus TNM improved prognostic performance as compared to TNM alone, both for VS 5-year DFS (C-index: 0.76 vs. 0.60) and OS (C-index: 0.74 vs. 0.64). CONCLUSIONS: Radiomics of b-MRI can help to predict recurrence and survival outcomes in HNSCC.

Cone-beam computed tomography-based radiomics in prostate cancer: a mono-institutional study.

PURPOSE: The purpose of the reported study was to investigate the value of cone-beam computed tomography (CBCT)-based radiomics for risk stratification and prediction of biochemical relapse in prostate cancer. METHODS: The study population consisted of 31 prostate cancer patients. Radiomics features were extracted from weekly CBCT scans performed for verifying treatment position. From the data, logistic-regression models were learned for establishing tumor stage, Gleason score, level of prostate-specific antigen, and risk stratification, and for predicting biochemical recurrence. Performance of the learned models was assessed using the area under the receiver operating characteristic curve (AUC-ROC) or the area under the precision-recall curve (AUC-PRC). RESULTS: Results suggest that the histogram-based Energy and Kurtosis features and the shape-based feature representing the standard deviation of the maximum diameter of the prostate gland during treatment are predictive of biochemical relapse and indicative of patients at high risk. CONCLUSION: Our results suggest the usefulness of CBCT-based radiomics for treatment definition in prostate cancer.

Patient-based low dose cone beam CT acquisition settings for prostate image-guided radiotherapy treatments on a Varian TrueBeam linear accelerator.

OBJECTIVE: To evaluate the performance of low dose cone beam CT (CBCT) acquisition protocols for image-guided radiotherapy of prostate cancer. METHODS: CBCT images of patients undergoing prostate cancer radiotherapy were acquired with the settings currently used in our department and two low dose settings at 50% and 63% lower exposure. Four experienced radiation oncologists and two radiation therapy technologists graded the images on five image quality characteristics. The scores were analysed through Visual Grading Regression, using the acquisition settings and the patient size as covariates. RESULTS: The low dose acquisition settings have no impact on the image quality for patients with body profile length at hip level below 100 cm. CONCLUSIONS: A reduction of about 60% of the dose is feasible for patients with size below 100 cm. The visibility of low contrast features can be compromised if using the low dose acquisition settings for patients with hip size above 100 cm. ADVANCES IN KNOWLEDGE: Low dose CBCT acquisition protocols for the pelvis, based on subjective evaluation of patient images.

Hypofractionated volumetric modulated arc therapy (VMAT) for fragile patients with oesophageal cancer.

PURPOSE: To evaluate the feasibility, safety, and dosimetric results of volumetric modulated arc therapy (VMAT) to deliver hypofractionated radiotherapy (RT) in oesophageal cancer patients, unfit for a multimodality curative strategy. PATIENTS/METHODS: From 2010 to 2017, 22 patients were treated with hypofractionated VMAT for palliative/symptomatic setting. The prescription dose was 40 Gy in 16 fractions (EQD2 41.7 Gy considering an α/ß ratio of 10 Gy, and 44 Gy considering an α/ß ratio of 3 Gy). RESULTS: Eight patients (36%) were symptomatic for grade 3 baseline dysphagia. RT was generally well tolerated, and no patient interrupted the daily treatment. Acute toxicity was generally mild; no G3 acute toxicities were reported. At the end of treatment, 5 patients (22.7%) experienced a stable dysphagia and 14 (63.6%) an improvement of baseline dysphagia, while 3 patients (13.7%) reported a worsening of oesophagitis. At a mean follow-up of 8.7 months, 15 patients (79%) had a complete clinical recovery (G0-1) of the symptomatic moderate/severe dysphagia. At 3 months after the end of RT, seven patients (31.8%) achieved a partial or complete response. Two coplanar arcs were employed for VMAT delivery. Dosimetric results were consistent in terms of both target coverage and normal tissue sparing. Finally, 1-year progression-free and overall survival was 20% and 27.3%, respectively. CONCLUSIONS: Hypofractionated VMAT was feasible, safe, and effective to deliver symptomatic radiation in locally advanced oesophageal cancer patients, non-suitable for a standard curative treatment.

Impact of 18F-FDG PET/CT in Staging Patients With Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Background: Molecular imaging methods are currently used in the management of patients with lung cancer. Compared to non-small cell lung cancer, less data are available about the impact of molecular imaging using fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in staging patients with small cell lung cancer (SCLC). Performing a systematic review and meta-analysis, we aimed to provide quantitative data about the impact of 18F-FDG PET/CT in staging SCLC. Methods: A comprehensive literature search of studies on the use of 18F-FDG PET/CT in patients with SCLC was performed. Three different databases were screened (PubMed/MEDLINE, EMBASE, and Cochrane library databases) until June 2019. Only articles describing the impact of 18F-FDG PET/CT in staging patients with SCLC were selected. A pooled analysis evaluating the change of binary SCLC staging (limited-stage vs. extensive-stage disease) using 18F-FDG PET/CT was carried out. Results: Nine articles including 721 patients with SCLC were included in the systematic review. Compared to conventional staging, a superior diagnostic accuracy of 18F-FDG PET/CT was found. A change of binary SCLC staging using 18F-FDG PET/CT was demonstrated in 15% (95% confidence interval, 9-21%) of patients with SCLC. Currently, it is not clearly demonstrated that the use of 18F-FDG PET/CT for staging may improve the survival outcome of patients with SCLC. Conclusions: 18F-FDG PET/CT is a useful molecular imaging method for staging patients with SCLC because it can change the management in a significant number of patients. More large prospective studies and cost-effectiveness analyses on the impact of 18F-FDG PET/CT in staging patients with SCLC are needed.

The role of radiotherapy in elderly women with early-stage breast cancer treated with breast conserving surgery.

OBJECTIVE: To analyze the impact of adjuvant radiotherapy (RT) on ipsilateral breast recurrence (IBR) and overall survival (OS) in patients older than 69 years with early-stage breast cancer. METHODS: From January 2007 to June 2015, we analyzed retrospectively 137 women with estrogen receptor-positive T1-2 invasive breast cancer, with negative axillary lymph nodes, dividing them into 2 subgroups: 70 to 79 years and older than 79 years. RESULTS: After a median follow-up of 43.2 months, the 3-year IBR-free survival in patients treated with surgery plus RT was 98.8% and 92.1% in patients treated with surgery alone, with a significant difference (p = .01). Radiotherapy did not impact overall survival (p = .10). A higher percentage of patients aged between 70 and 79 years received RT after conservative surgery if compared with the older subgroup (p < .01). CONCLUSIONS: In elderly women, adjuvant RT reduced the IBR, but did not improve OS.

Concurrent chemoradiation with volumetric modulated Arc therapy of patients treated for anal cancer-acute toxicity and treatment outcome.

BACKGROUND: to report the acute toxicity and clinical results in patients with anal cancer treated with volumetric modulated arc therapy (VMAT) concomitant with chemotherapy. METHODS: A cohort of 21 patients with histologically confirmed squamous cell carcinoma of the anal canal was treated with VMAT and chemotherapy. Dose prescription was 39.6 Gy, 1.8 Gy/ fraction for the elective nodal PTV, the macroscopic (tumor and involved lymph nodes) PTV doses were 14.4 Gy up to a total dose of 54 Gy in 4 patients and 19.8 up to 59.4 Gy in 15 patients. One patient received a boost dose of 18 Gy up to a total dose of 57.6 Gy and another one was treated with 36 Gy and boost of 19.8 Gy up to a total dose of 55.8 Gy. Chemotherapy with MMC and 5-FU/Capecitabine was administered concomitantly. End points were local control (LC), disease-free survival (DFS) and overall survival (OS). RESULTS: Median follow-up time was 35.5 months. Two year OS was 91%, DFS was 73% and LRC was 81%. Acute dermatological toxicity G3 was recorded in one patient, ten patients (47.6%) experienced a G2 skin toxicity, while G1 toxicity was registered in eight patients (38%). One patient developed Grade 3 acute gastrointestinal (GI) toxicity, two patients (9.5%) experienced grade 2 acute GI toxicity and ten patients (47.6%) G1 toxicity. Acute genitourinary toxicity G1 was recorded in ten patients (47.6%). CONCLUSIONS: Our results support VMAT as standard radiotherapy technique in the treatment of patients with anal cancer.

Outcome and prognostic factors in 110 consecutive patients with primary uterine leiomyosarcoma: A Rare Cancer Network study.

OBJECTIVE: Primary uterine leiomyosarcomas (ULMS) are rare, and the optimal treatment is controversial. We aimed to assess the outcome and prognostic factors in a multicenter population of women treated for primary ULMS. METHODS: We retrospectively collected data of 110 women treated in 19 institutions of the Rare Cancer Network (RCN). Inclusion criteria consisted of a pathology report confirming the diagnosis of ULMS, aged 18-80 years, complete International Federation of Gynecology and Obstetrics (FIGO) stage information, complete information on treatment, and a minimum follow-up of 6 months. Local control (LC) and locoregional control (LRC), overall survival (OS) and disease-free survival (DFS) rates were computed using the Kaplan-Meier method. Univariate analysis was implemented using the log rank test, and multivariate analysis using the Cox model. RESULTS: All patients underwent surgery. Seventy-five patients (68%) received adjuvant radiotherapy (RT), including brachytherapy in 18 (16%). Seventeen patients (15%) received adjuvant chemotherapy. Median follow-up was 58 (range, 6-240) months. Five-year OS and DFS rates were 50% and 34%, and LC and LRC rates were 88% and 72%, respectively. On multivariate analysis, independent favorable prognostic factors were younger age, FIGO stage I, small tumor size, previous uterine disease, and no vascular invasion for OS and DFS. FIGO stage was the only favorable factor influencing LRC. Adjuvant local or systemic treatments did not improve the outcomes. Eight patients treated with RT presented a grade 3 acute toxicity, and only one patient with grade 3 late toxicity. CONCLUSIONS: In this large population of primary ULMS patients, we found good results in terms of LC and LRC. Nevertheless, OS remains poor, mainly due to the occurrence of distant metastases. An early diagnosis seemed to improve the prognosis of the patients. Adjuvant local or systemic treatments, or more aggressive surgical procedures such as the Wertheim procedure, did not seem to impact the outcome.

Impact of preoperative radiotherapy on survival in locally advanced rectal cancer: an observational population-based study from the South of Switzerland.

Preoperative radiotherapy (RT) followed by surgery is widely accepted in the treatment of locally advanced rectal cancer (LARC). This study aimed to estimate at the population-based level the impact of preoperative RT on overall survival (OS) and cancer-specific survival (CSS) in LARCs diagnosed in Southern Switzerland between 1996 and 2007. All patients with LARC were selected from the Ticino Cancer Registry database. Patients were categorized according to the first administered treatment: preoperative radiotherapy (RT) followed by surgery (RT+) versus surgery (RT-). Clinical-pathological characteristics and 5-year OS and CSS were analysed. Among 384 patients with LARC, 54% underwent preoperative RT, occurring more frequently in the mid-distal part of the rectum compared with the RT- group (74.8 vs. 29.8%, respectively). Both 5-year OS and CSS significantly improved in RT+ patients (OS: 68 vs. 54%, respectively; CSS: 71 vs. 63%, respectively). The adjusted hazard ratio for all death was equal to 0.66 (95% confidence interval: 0.46; 0.97); similarly, the hazard ratio for cancer-specific death was 0.63 (95% confidence interval: 0.39; 0.99). These observational population-based results, after controlling for most important diagnostic and clinical prognostic factors, confirm the benefit of preoperative RT of LARC, even if the magnitude seems greater than expected in clinical trials results. Additional studies are needed, particularly with regard to the possible effect of standardized staging procedure and multidisciplinary discussion on patient outcome.

Cranio-spinal irradiation with volumetric modulated arc therapy: a multi-institutional treatment experience.

PURPOSE: To report the treatment of cranio-spinal irradiation (CSI) with volumetric modulated arc therapy (RapidArc) in adults and a child. MATERIALS AND METHODS: Five patients from 5 institutions were treated with CSI using RapidArc technology. Patient age varied between 7 and 45 years. The lengths of the planning target volumes (PTV) and dose prescriptions ranged from 54.6 to 78.4 cm, and from 12 to 36 Gy, respectively. Different arc arrangements were used, with two or three isocentres, from two to six modulated arcs, for patient positioned either in prone (n=3) or supine position (n=2). Doses to PTV, organs at risk and non-target tissue are reported for each of the five patients. Data concerning imaging strategy and pre-treatment quality assurance are also reported. RESULTS: The mean conformity index CI(95%) was 1.05 ± 0.05 (range: 1.00, 1.13). Mean doses to the lenses, lungs, heart, and kidneys were, respectively, 7.6 ± 1.6, 6.6 ± 3.0, 5.7 ± 2.3, and 6.1 ± 2.1 Gy, keeping those value acceptably low. Mean non-target tissue dose was 21.0 ± 3.8% (5.6 ± 1.8 Gy, range: 3.0-8.1 Gy). All patients were successfully planned and treated with RapidArc. CONCLUSIONS: RapidArc techniques achieved highly conformal treatment plans for 5 adults or paediatric patients. Beam-on time was short, and RapidArc plans were satisfactorily delivered to all presented patients.

Early clinical experience of radiotherapy of prostate cancer with volumetric modulated arc therapy.

BACKGROUND: To report about initial clinical experience in radiation treatment of carcinoma of prostate with volumetric modulated arcs with the RapidArc (RA) technology. METHODS: Forty-five patients with a median age of 72 +/- 3, affected by prostate carcinoma (T1c: 22 patients, T2a-b: 17 patients, T3a-b: 6 patients. N0: 43 patients, N1-Nx: 2 patients, all M0), with initial PSA of 10.0 +/- 3.0 ng/mL, were treated with RapidArc in a feasibility study. All patients were treated with single arc using 6MV photons. Dose prescription ranged between 76 (7 patients) and 78 Gy (38 patients) in 2 Gy/fraction. Plan quality was assessed by means of Dose Volume Histogram (DVH) analysis. Technical parameters of arcs and pre-treatment quality assurance results (Gamma Agreement Index, GAI) are reported to describe delivery features. Early toxicity was scored (according to the Common Terminology Criteria of Adverse Effects scale, CTCAE, scale) at the end of treatment together with biochemical outcome (PSA). RESULTS: From DVH data, target coverage was fulfilling planning objectives: V95% was in average higher than 98% and V107% approximately 0.0% (D2% approximately 104.0% in average). Homogeneity D5%-D95% ranged between 6.2 +/- 1.0% to 6.7 +/- 1.3%. For rectum, all planning objectives were largely met (e.g. V70Gy = 10.7 +/- 5.5% against an objective of < 25%) similarly for bladder (e.g. D2% = 79.4 +/- 1.2 Gy against an objective of 80.0 Gy). Maximum dose to femurs was D2% = 36.7 +/- 5.4 Gy against an objective of 47 Gy. Monitor Units resulted: MU/Gy = 239 +/- 37. Average beam on time was 1.24 +/- 0.0 minutes. Pre-treatment GAI resulted in 98.1 +/- 1.1%. Clinical data were recorded as PSA at 6 weeks after RT, with median values of 0.4 +/- 0.4 ng/mL. Concerning acute toxicity, no patient showed grade 2-3 rectal toxicity; 5/42 (12%) patients experienced grade 2 dysuria; 18/41 (44%) patients preserved complete or partial erectile function. CONCLUSION: RapidArc proved to be a safe, qualitative and advantageous treatment modality for prostate cancer.

Neo-adjuvant chemo-radiation of rectal cancer with volumetric modulated arc therapy: summary of technical and dosimetric features and early clinical experience.

BACKGROUND: To report about initial technical and clinical experience in preoperative radiation treatment of rectal cancer with volumetric modulated arcs with the RapidArc (RA) technology. METHODS: Twenty-five consecutive patients (pts) were treated with RA. All showed locally advanced rectal adenocarcinoma with stage T2-T4, N0-1. Dose prescription was 44 Gy in 22 fractions (or 45 Gy in 25 fractions). Delivery was performed with single arc with a 6 MV photon beam. Twenty patients were treated preoperatively, five did not receive surgery. Twenty-three patients received concomitant chemotherapy with oral capecitabine. A comparison with a cohort of twenty patients with similar characteristics treated with conformal therapy (3DC) is presented as well. RESULTS: From a dosimetric point of view, RA improved conformality of doses (CI95% = 1.1 vs. 1.4 for RA and 3DC), presented similar target coverage with lower maximum doses, significant sparing of femurs and significant reduction of integral and mean dose to healthy tissue. From the clinical point of view, surgical reports resulted in a down-staging in 41% of cases. Acute toxicity was limited to Grade 1-2 diarrhoea in 40% and Grade 3 in 8% of RA pts, 45% and 5% of 3DC pts, compatible with known effects of concomitant chemotherapy. RA treatments were performed with an average of 2.0 vs. 3.4 min of 3DC. CONCLUSION: RA proved to be a safe, qualitatively advantageous treatment modality for rectal cancer, showing some improved results in dosimetric aspects.

Accelerated versus conventional fractionated postoperative radiotherapy for advanced head and neck cancer: results of a multicenter Phase III study.

PURPOSE: To determine whether, in the postoperative setting, accelerated fractionation (AF) radiotherapy (RT) yields a superior locoregional control rate compared with conventional fractionation (CF) RT in locally advanced squamous cell carcinomas of the oral cavity, oropharynx, larynx, or hypopharynx. METHODS AND MATERIALS: Patients from four institutions with one or more high-risk features (pT4, positive resection margins, pN >1, perineural/lymphovascular invasion, extracapsular extension, subglottic extension) after surgery were randomly assigned to either RT with one daily session of 2 Gy up to 60 Gy in 6 weeks or AF. Accelerated fractionation consisted of a "biphasic concomitant boost" schedule, with the boost delivered during the first and last weeks of treatment, to deliver 64 Gy in 5 weeks. Informed consent was obtained. The primary endpoint of the study was locoregional control. Analysis was on an intention-to-treat basis. RESULTS: From March 1994 to August 2000, 226 patients were randomized. At a median follow-up of 30.6 months (range, 0-110 months), 2-year locoregional control estimates were 80% +/- 4% for CF and 78% +/- 5% for AF (p = 0.52), and 2-year overall survival estimates were 67% +/- 5% for CF and 64% +/- 5% for AF (p = 0.84). The lack of difference in outcome between the two treatment arms was confirmed by multivariate analysis. However, interaction analysis with median values as cut-offs showed a trend for improved locoregional control for those patients who had a delay in starting RT and who were treated with AF compared with those with a similar delay but who were treated with CF (hazard ratio = 0.5, 95% confidence interval 0.2-1.1). Fifty percent of patients treated with AF developed confluent mucositis, compared with only 27% of those treated with CF (p = 0.006). However, mucositis duration was not different between arms. Although preliminary, actuarial Grade 3+ late toxicity estimates at 2 years were 18% +/- 4% and 27% +/- 6% for CF and AF, respectively (p = 0.10). CONCLUSION: Accelerated fractionation does not seem to be worthwhile for squamous cell carcinoma of the head and neck after resection; however, AF might be an option for patients who delay starting RT.

Hyperfractionated radiotherapy for T2N0 glottic carcinoma: a retrospective analysis at 10 years follow-up in a series of 60 consecutive patients.

AIMS AND BACKGROUND: To report results of hyperfractionated radiotherapy for T2N0 glottic carcinoma at a single institution after extended follow-up. METHODS: Between 1980 and 1988 at Varese University Hospital, 60 consecutive patients with T2N0 glottic carcinoma received exclusive radiotherapy consisting of 1.5 Gy/fraction twice a day. Treatment gaps during the radiotherapy course were allowed according to individual tolerance. This policy resulted in a wide range of elapsed treatment time: median, 5.7 weeks; range, 3.7-8.9. Median follow-up is 9.8 years. RESULTS: As a result of dose/time distribution, 16, 20 and 24 patients received an average weekly dose rate of <10 Gy/week, equal to 10 Gy/week or >10 Gy/week, respectively. Mean total dose for each group was 62.8 Gy, 63.7 Gy and 63.8 Gy, respectively. Five-year local-regional control was 69 +/- 6% (95% CI); ultimate local-regional control, including salvage surgery, was 78 +/- 5%. All failures were at the primary site, and no patient developed neck recurrence as first site of failure. The actuarial incidence of grade 2-3 late reactions at 5 years was 42 +/- 6%. Most late toxicity events were grade 2: only 2 patients developed grade 3 reactions and none grade 4. None of the several clinical and treatment-related variables showed any statistically significant impact on local-regional control or late toxicity at univariate and multivariate analysis. In particular, 3-year local-regional control rates were 73 +/- 11%, 84 +/- 8% and 69 +/- 10% for an average weekly dose rate of <10 Gy/week, equal to 10 Gy/week and >10 Gy/week, respectively (not significantly different). CONCLUSIONS: At a very long follow-up, the hyperfractionated regimen tested in the study was shown to be effective and devoid of major complications, provided individual patient acute tolerance is carefully taken into account. Also, time factor did not affect outcome in this series.

Are international guidelines for the prescription of adjuvant treatment for early breast cancer followed in clinical practice? Results of a population-based study on 1547 patients.

AIMS AND BACKGROUND: The results of several randomized trials and meta-analyses have been reported on adjuvant treatment for early breast cancer and treatment guidelines have been defined accordingly, but detailed data are lacking on the appropriateness of treatment prescription in clinical practice. METHODS: We performed a prospective, observational, multicenter study to monitor the prescription, delivery and effectiveness of radiotherapy following conservative surgery for early breast cancer; 1610 patients treated with postoperative radiation to the breast in 1997 were entered by 12 centers in Lombardy, Italy. Here we report the results of a secondary analysis focused on the prescription of medical adjuvant treatment (1547 eligible patients). RESULTS: Chemotherapy only was prescribed to 526 patients (33%), hormonal therapy only to 539 (33%), and both treatments to 85 patients (5%); 460 women (29%) received no medical adjuvant treatment. We compared the collected data with guidelines defined in 1995 by the St Gallen Consensus Conference. Undertreatment was most frequent in node-negative patients at intermediate/high risk, no treatment (instead of tamoxifen or chemotherapy) being prescribed in 21-45% of cases. Node-negative patients at low risk, on the other hand, were overtreated with tamoxifen in 31% of cases. In node-positive, premenopausal women compliance with guidelines was far better, with a 91-96% rate of chemotherapy prescription. In node-positive, postmenopausal, estrogen receptor-positive patients chemotherapy was unduly prescribed in as many as 56% of cases. Comparison of clinical practice with the next version of the guidelines (1998) showed a somewhat better compliance. CONCLUSIONS: Despite the availability of official and authoritative guidelines, adjuvant treatment prescription for early breast cancer in Lombardy in 1997 was suboptimal, especially in well-defined subgroups of patients.