Lymph node ratio and surgical quality are strong prognostic factors of rectal cancer: results from a single referral centre.

AIM: Nodal stage is a strong prognostic factor of oncological outcome of rectal cancer. To compensate for the variation in total number of harvested nodes, calculation of the lymph node ratio (LNR) has been advocated. The aim of the study was to compare the impact, on the long-term oncological outcome, of the LNR with other predictive factors, including the quality of total mesorectal excision (TME) and the state of the circumferential resection margin. METHOD: Consecutive patients having elective surgery for nonmetastatic rectal cancer were extracted from a prospectively maintained database. Retrospective uni- and multivariate analyses were performed based on patient-, surgical- and tumour-related factors. The prognostic value of the LNR on overall survival (OS) and on overall recurrence-free survival (ORFS) was assessed and a cut-off value was determined. RESULTS: From 1998 to 2013, out of 456 patients, 357 with nonmetastatic disease were operated on for rectal cancer. Neoadjuvant radiochemotherapy was administered to 66.7% of the patients. The mean number of lymph nodes retrieved was 12.8 ± 8.78 per surgical specimen. A lower lymph node yield was obtained in patients who received neoadjuvant chemoradiotherapy (11.8 vs 14.2; P = 0.014). The 5-year ORFS was 71.8% and the 5-year OS was 80.1%. Multivariate analysis confirmed LNR, the quality of TME and age to be independent prognostic factors of OS. LNR, age and perineural infiltration were independently associated with ORFS. Low- and high-risk patients could be discriminated using an LNR cut-off value of 0.2. CONCLUSION: LNR is an independent prognostic factor of OS and ORFS. In line with the principles of optimal surgical management, the quality of TME and lymph node yield are essential technical requirements.

Clinical radiotherapy audits in Belgium, 2011-2014.

Systematic clinical radiotherapy audits have been introduced in Belgium in 2011, as part of the Federal Cancer Plan. This is in compliance with article 11 of the 97/43 Council directive of Euratom states, translated into the Belgian legislation by royal decree in 2002. The principle of clinical audits has thus been part of the federal legal requirements for more than 10 years. However, its application had to wait for the development of a practical approach: what authority will audit, who will be the auditors, along which methodology, at what frequency, etc. Since 2002, the Federal College of Radiotherapy has the mission to monitor quality of radiotherapy at large. It was therefore decided after discussions with the relevant administration at the Ministry of Health and the Federal Agency for Nuclear Control that the College would practically organise the audits. Early in the 2000s, the IAEA developed a manual for comprehensive audits, as a tool for quality improvement. Auditors were professionals of the domain and the audit visit took the form of a peer review. Great care was taken to assemble an audit party able to cover all aspects of clinical radiotherapy with a radiation oncologist, a medical physicist, a radiation therapist and, on demand, a quality officer. The IAEA manual contains a series of questionnaires to be prepared by the audited centre in advance (pre-audit and self-assessment), indicating what specific areas the auditors would assess. It is also a template for the auditors, ensuring that no area is left aside or forgotten during the site visit. The report, at the end of the visit, is drafted according to a specific report template, also developed by IAEA. Several members of the Belgian radiotherapy community have developed their auditor's skills by participating to the IAEA audit program; they are the core of the auditor Belgian team.

Relevance of a systematic geriatric screening and assessment in older patients with cancer: results of a prospective multicentric study.

BACKGROUND: To evaluate the large-scale feasibility and usefulness of geriatric screening and assessment in clinical oncology practice by assessing the impact on the detection of unknown geriatric problems, geriatric interventions and treatment decisions. PATIENTS AND METHODS: Eligible patients who had a malignant tumour were ≥70 years old and treatment decision had to be made. Patients were screened using G8; if abnormal (score ≤14/17) followed by Comprehensive Geriatric Assessment (CGA). The assessment results were communicated to the treating physician using a predefined questionnaire to assess the topics mentioned above. RESULTS: One thousand nine hundred and sixty-seven patients were included in 10 hospitals. Of these patients, 70.7% had an abnormal G8 score warranting a CGA. Physicians were aware of the assessment results at the time of treatment decision in two-thirds of the patients (n = 1115; 61.3%). The assessment detected unknown geriatric problems in 51.2% of patients. When the physician was aware of the assessment results at the time of decision making, geriatric interventions were planned in 286 patients (25.7%) and the treatment decision was influenced in 282 patients (25.3%). CONCLUSION: Geriatric screening and assessment in older patients with cancer is feasible at large scale and has a significant impact on the detection of unknown geriatric problems, leading to geriatric interventions and adapted treatment.

Quality of care indicators in rectal cancer.

Quality of health care is a hot topic, especially with regard to cancer. Although rectal cancer is, in many aspects, a model oncologic entity, there seem to be substantial differences in quality of care between countries, hospitals and physicians. PROCARE, a Belgian multidisciplinary national project to improve outcome in all patients with rectum cancer, identified a set of quality of care indicators covering all aspects of the management of rectal cancer. This set should permit national and international benchmarking, i.e. comparing results from individual hospitals or teams with national and international performances with feedback to participating teams. Such comparison could indicate whether further improvement is possible and/or warranted.

Experimental and theoretical dosimetry of a new polymer encapsulated iodine-125 source--SmartSeed: dosimetric impact of fluorescence x rays.

PURPOSE: The detailed study of a new permanent iodine-125 brachytherapy source, SmartSeed, is presented in this article. It is the first iodine seed made with biocompatible polymer and is manufactured by the IBt-Bebig group. METHODS: Three dosimetric studies have been performed: The first one used thermoluminescent detectors in a solid water phantom with NIST (National Institute of Standards and Technology, USA) calibrated seeds, and two separate studies were of Monte Carlo photon transport calculations (MCNP5 code). The TG-43U1 protocol was applied to derive dosimetric parameters for clinical applications. RESULTS: The radial dose function g(r) was determined at different distances ranging from 0.5 to 10 cm; and the anisotropy function F(r, theta) at angles ranging from 0 degrees to 350 degrees in 10 degrees increments. Monte Carlo calculations were performed in liquid water to obtain values for lambda, g(r), F(r, theta), and phi(an)(r) as recommended by the TG-43U1 protocol for use in treatment planning system software. SmartSeed's biocompatible polymer capsule permits fluorescence x rays (3, 5, and 12 keV), generated by lead glass marker, to be present in the emission spectrum, influencing the dose rate constant. The impact on near field dosimetry in water from these x rays was also investigated and reported. The capsule also attenuates iodine-125 energies much less than typical titanium encased sources, resulting in a highly isotropic source. CONCLUSIONS: SmartSeed has a dose rate constant of 0.895 +/- 7.3% cGy h(-1) U(-1), a radial dose function nearly identical to the IBt-Bebig model I25.S06 seed, and a highly isotropic dose distribution. Fluorescence x rays account for the relatively low value of lambda, yet their variable contribution to dosimetry arising from seed dimensional uncertainties is estimated to be < 0.2%.

EORTC elderly task force position paper: approach to the older cancer patient.

As a result of an increasing life expectancy, the incidence of cancer cases diagnosed in the older population is rising. Indeed, cancer incidence is 11-fold higher in persons over the age of 65 than in younger ones. Despite this high incidence of cancer in older patients, solid data regarding the most appropriate approach and best treatment for older cancer patients are still lacking, mostly due to under-representation of these patients in prospective clinical trials. The clinical behaviour of common malignant diseases, e.g. breast, ovarian and lung cancers, lymphomas and acute leukaemias, may be different in older patients because of intrinsic variation of the neoplastic cells and the ability of the tumour host to support neoplastic growth. The decision to treat or not these patients should be based on patients' functional age rather than the chronological age. Assessment of patients' functional age includes the evaluation of health, functional status, nutrition, cognition and the psychosocial and economic context. The purpose of this paper is to focus on the influence of age on cancer presentation and cancer management in older cancer patients and to provide suggestions on clinical trial development and methodology in this population.

Feasibility of radiotherapy with concomitant gemcitabine and oxaliplatin in locally advanced pancreatic cancer and distal cholangiocarcinoma: a prospective dose finding phase I-II study.

BACKGROUND: The prognosis of pancreaticobiliary tumors is poor. The aim was to assess the feasibility of radiotherapy (RT) and concomitant gemcitabine and oxaliplatin in locally advanced pancreatic cancer and distal cholangiocarcinoma. PATIENTS AND METHODS: Twenty-two patients with locally advanced pancreatic (n = 17) or biliary tract cancer (n = 5) were included. They received two cycles of gemcitabine/oxaliplatin followed by 5 weeks of RT in combination with a weekly fixed dose gemcitabine and an escalating dose of oxaliplatin from 40 up to 70 mg/m(2). National Cancer Institute-Common Toxicity Criteria 3.0 was used to score weekly the treatment-related toxicity. RESULTS: The patients treated at a dose of 40 mg/m(2) of oxaliplatin had no dose-limiting toxicity. At 50 mg/m(2), two patients developed grade 4 thrombocytopenia. Nine patients received 60 mg/m(2), one developed grade 4 thrombocytopenia. Grade 4 thrombocytopenia in two patients and grade 3 diarrhea in one patient were observed with 70 mg/m(2). Median time to progression was 8 months and median overall survival was 17 months. CONCLUSIONS: RT in combination with gemcitabine and oxaliplatin is feasible in patients with locally advanced pancreaticobiliary cancer. The reported time to progression underlines the potential activity of this regimen. The dose of 60 mg/m(2) of oxaliplatin can be considered as the recommended dose.

An experimental palladium-103 seed (OptiSeedexp) in a biocompatible polymer without a gold marker: characterization of dosimetric parameters including the interseed effect.

Permanent implantation of 125I (iodine) or 103Pd (palladium) sources is a popular treatment option in the management of early stage prostate cancer. New sources are being developed, some of which are being marketed for different clinical applications. A new technique of adjuvant stereotactic permanent seed breast implant, similar to that used in the treatment of prostate cancer, has been proposed by [N. Jansen et al., Int. J. Radiat. Oncol. Biol. Phys. 67, 1052-1058 (2007)] with encouraging results. The presence of artifacts from the metallic seeds, however, can disturb follow-up imaging. The development of plastic seeds has reduced these artifacts. This paper presents a feasibility study of the advantages of palladium-103 seeds, encapsulated with a biocompatible polymer, for future clinical applications, and on the effect of the gold marker on the dosimetric characteristics of such seeds. Experimental palladium seeds, OptiSeedexp, were manufactured by International Brachytherapy (IBt), Seneffe, Belgium, from a biocompatible polymer, including the marker. Apart from the absence of a gold marker, the studied seed has an identical design to the OptiSeed103 [Phys. Med. Biol. 50, 1493-1504 (2005)]; [Appl. Radiat. Isot. 63, 311-321 (2005)]. Polymer encapsulation was preferred by IBt in order to reduce the quantity of radioactive material needed for a given dose rate and to reduce the anisotropy of the radiation field around the seed. In addition, this design is intended to decrease the interseed effects that can occur as a result of the marker and the encapsulation. Dosimetric measurements were performed using LiF thermoluminescent dosimeters (1 mm3) in solid water phantoms (WT1). Measured data were compared to Monte Carlo simulated data in solid water using the MCNP code, version 4C. Updated cross sections [Med. Phys. 30, 701-711 (2003)] were used. As the measured and calculated data were in agreement, Monte Carlo calculations were then performed in liquid water to obtain relevant dosimetric data as required by TG-43U1 recommendations. Comparison of the results with previous studies of OptiSeed103 [Phys. Med. Biol. 50, 1493-1504 (2005)]; [Appl. Radiat. Isot. 63, 311-321 (2005)], and of InterSource103 [Appl. Radiat. Isot. 57, 805-811 (2002)] showed very good agreement for the dose rate constant and for the radial dose function. With respect to the anisotropy function, the relative dose (anisotropy value relative to 90 degrees) from the polymer seed at a distance of 3 cm was close to unity (105%) at 0 degrees, whereas the relative values for the OptiSeed103 with a gold marker and the titanium-encapsulated InterSource103 seed decreased to 70% and 40%, respectively. The interseed effect from one seed was negligible and in the order of calculation uncertainty, making calculation of the dose rate distribution of the studied seeds, according to TG43U1 recommendations, more accurate and closer to reality. This feasibility study shows that due to the low energy of palladium-103, the negligible interseed effect and the reduced artifacts in postimplant medical imaging, this experimental plastic seed would be a good source for breast brachytherapy. This feasibility study was carried out in collaboration with IBt and will be continued with a study of its visibility in different tissues.

Phase I/II study of preoperative cetuximab, capecitabine, and external beam radiotherapy in patients with rectal cancer.

BACKGROUND: To assess the safety and preliminary efficacy of concurrent radiotherapy, capecitabine, and cetuximab in the preoperative treatment of patients with rectal cancer. PATIENTS AND METHODS: Forty patients with rectal cancer (T3-T4, and/or N+, endorectal ultrasound) received preoperative radiotherapy (1.8 Gy, 5 days/week for 5 weeks, total dose 45 Gy, three-dimensional conformal technique) in combination with cetuximab [initial dose 400 mg/m(2) intravenous given 1 week before the beginning of radiation followed by 250 mg/m(2)/week for 5 weeks] and capecitabine for the duration of radiotherapy (650 mg/m(2) orally twice daily, first dose level; 825 mg/m(2) twice daily, second dose level). RESULTS: Four and six patients were treated at the first and second dose level of capecitabine, respectively. No dose-limiting toxicity occurred. Thirty additional patients were treated with capecitabine at 825 mg/m(2) twice daily. The most frequent grade 1/2 side-effects were acneiform rash (87%), diarrhea (65%), and fatigue (57%). Grade 3 diarrhea was found in 15%. Three grade 4 toxic effects were recorded: one myocardial infarction, one pulmonary embolism, and one pulmonary infection with sepsis. Two patients (5%) had a pathological complete response. CONCLUSIONS: Preoperative radiotherapy in combination with capecitabine and cetuximab is feasible with some patients achieving pathological downstaging.

Factors that influence cancer patients' anxiety following a medical consultation: impact of a communication skills training programme for physicians.

BACKGROUND: No study has yet assessed the impact of physicians' skills acquisition after a communication skills training programme on the evolution of patients' anxiety following a medical consultation. This study aimed to compare the impact, on patients' anxiety, of a basic communication skills training programme (BT) and the same programme consolidated by consolidation workshops (CW), and to investigate physicians' communication variables associated with patients' anxiety. PATIENTS AND METHODS: Physicians, after attending the BT, were randomly assigned to CW or to a waiting list. The control group was not a non-intervention group. Consultations with a cancer patient were recorded. Patients' anxiety was assessed with the State Trait Anxiety Inventory before and after a consultation. Communication skills were analysed according to the Cancer Research Campaign Workshop Evaluation Manual. RESULTS: No statistically significant change over time and between groups was observed. Mixed-effects modelling showed that a decrease in patients' anxiety was linked with screening questions (P = 0.045), physicians' satisfaction about support given (P = 0.004) and with patients' distress (P < 0.001). An increase in anxiety was linked with breaking bad news (P = 0.050) and with supportive skills (P = 0.013). No impact of the training programme was observed. CONCLUSIONS: This study shows the influence of some communication skills on the evolution of patients' anxiety. Physicians should be aware of these influences.

Phase II study of preoperative oxaliplatin, capecitabine and external beam radiotherapy in patients with rectal cancer: the RadiOxCape study.

BACKGROUND: Preoperative radiotherapy has been shown to decrease the local recurrence rate of patients with locally advanced rectal cancer. Capecitabine and oxaliplatin are both active anticancer agents in the treatment of patients with advanced colorectal cancer and have radiosensitizing properties. Therefore, these drugs would be expected to improve effectiveness of preoperative radiotherapy in terms of local control and prevention of distant metastases. PATIENTS AND METHODS: Forty patients with rectal cancer (T3-T4 and/or N+) received radiotherapy (1.8 Gy, 5 days a week over 5 weeks, total dose 45 Gy, 3D conformational technique) in combination with intravenous oxaliplatin 50 mg/m2 once weekly for 5 weeks and oral capecitabine 825 mg/m2 twice daily on each day of radiation. Surgery was performed 6-8 weeks after completion of radiotherapy. The main end points were safety and efficacy as assessed by the pathological complete response (pCR). RESULTS: The most frequent grade 3/4 adverse event was diarrhea, occurring in 30% of patients. pCR was found in five (14%) patients. According to Dworak's classification, good regression was found in six (18%) additional patients. CONCLUSIONS: Combination of preoperative radiotherapy with capecitabine and oxaliplatin is feasible for downstaging rectal cancer.

Optimization of a breast implant in Brachytherapy PDR: validation with Monte Carlo simulation and measurements with TLDs and GafChromic films.

BACKGROUND AND PURPOSE: The calculation of the dose distribution of Brachytherapy breast implant has been carried out in accordance with the Paris System (PS) in the majority of the radiotherapy departments in Europe. PDR (Pulsed Dose Rate) has lead to an improvement of the treatment procedure, optimization tools, however, allow an improvement of the treatment technique. The goal of this study was to perform a dosimetric verification of an optimized seven needles implant and to try to decrease the active length while preserving the same treatment volume. This corresponds to a ratio "treated length/active length" (L(t)/L(a)) that tends towards 1. MATERIAL AND METHODS: A dosimetry phantom was made of polystyrene, capable of receiving the implant, TLDs (LiF100 1mm(3) micro cubes) and films (GafChromic MD 55-2). Dose distributions for one source position and for the implant in conformity with the PS were calculated, utilizing version 14.2 of the Plato TPS (Nucletron); the remote afterloading system was a microSelectron-PDR (Nucletron). MCNP (Monte Carlo N-Particles transport) modeling was used for various configurations to evaluate the influence of the composition of the medium, of the presence of the needles and the lack of scatter. RESULTS: The benefit of the optimization was shown by the determination of a L(t)/L(a) factor of 1.05 instead of 0.7 for the standard PS. The dose distributions calculated by Plato are in agreement with TLD and film measurements for the optimization and the PS (<5%). The TPS results were confirmed by MC calculation as well as by measurements. MC calculations also showed that only the lack of scatter had a significant influence on the dose received by the skin (20%) CONCLUSIONS: The optimization brings a significant benefit in protecting the skin and in homogeneity of the dose distribution in the treated volume. Through MC simulation, this work made it possible to update a parameter significantly influencing dose distribution calculations: the lack of scattering.

The opinion of general practitioners on the treatment of prostate and breast cancer in elderly people: results of a survey based on clinical models.

AIMS: Several publications have reported age-related differences in the management of people with cancer. Most data have been derived retrospectively from hospital or cancer-centre databases. The aim of the present study was to identify major decisional factors observed in general practitioner (GP) practices, outside the hospital setting, regarding the clinical management of patients with prostate and breast cancer. MATERIALS AND METHODS: During three national GP meetings in Belgium, questionnaires presenting two simulated patient cases were presented to GPs who were asked two questions: one regarding further staging and referral of the case and the second regarding the treatment of the case. A total of 678 questionnaires were distributed. GPs received two randomly selected cases each: a breast cancer history and a prostate cancer history. Three variables were assessed simultaneously: age, performance status and medical history (comorbidity). RESULTS: The analysis indicated that elderly patients were more likely to be referred for non-curative treatment (OR 13.71; 95% CI 5.67-33.12; P < 0.0001 for prostate cancer and OR 17.67; 95% CI 4.04-77.31; P < 0.0001 for breast cancer). The other variables (performance status and medical history) did not affect treatment orientation. However, GPs were prepared to seek assistance from oncologists in both cases, irrespective of the patient's age. CONCLUSION: Age seems to be more important among GPs in deciding how to manage cancer patients than performance status and comorbidity. This is a very common prejudice. They are, nevertheless, inclined to refer people with cancer to oncologists independently of the patient's age.

Impact of medical specialists' locus of control on communication skills in oncological interviews.

Although is it widely recognised that physicians' characteristics could influence their communication styles, no empirical evidence is currently available. No studies are available on the impact of physicians' locus of control (LOC) on their communication skills. LOC is a generalised belief regarding the extent to which life outcomes are controlled by an individual's actions (internal LOC) or by external forces such as luck, fate or other individuals (external LOC). It was hypothesised that physicians with external LOC would take more into account others' concerns than physicians with internal LOC and would consequently use more appropriate assessment, informative and supportive functions. A total of 81 medical specialists were assessed in a simulated interview and a clinical interview. Communication skills were rated according to the Cancer Research Campaign Workshop Evaluation Manual. LOC was assessed using the Rotter I-E scale. Communication skills of the upper and lower quartiles of physicians in respect of their scores on this scale were compared using Student's t-test. Results show that physicians with external LOC give more appropriate information than physicians with internal LOC in simulated interviews (P=0.011) and less premature information than physicians with internal LOC in clinical interviews (P=0.015). This result provides evidence that physicians' LOC can influence their communication styles in oncological interviews and in particular the way they provide information to the patient.

Dosimetric study of a new palladium seed.

In this paper, the dosimetric parameters for a new palladium seed design: the InterSource(103,)(1) are presented as recommended by the AAPM in the TG-43 formalism. Measurements are made with LiF thermoluminescent dosimeters (size of 1mm(3)) in solid water phantoms WT1 to obtain the dose constant, the radial dose function and the anisotropy function. The TLD were calibrated at 6 MV and an energy correction factor of 1.40 has been applied. The same dose parameters are also obtained by Monte Carlo calculations (MCNP4B) in solid water and in liquid water. The calculated and the measured TG-43 functions for solid water are in excellent agreement. In WT1, the calculated dose rate constant is 0.657+/-1% and the measured value is 0.672+/-7%. The calculated value for water is 0.692+/-1%. The comparison with the previous study (Med. Phys. 27(5) (2000)) shows a very good agreement for the dose rate constant. The agreement for the radial function is poorer. For the measurements, it can be due to the difference of TLD settings. For the calculations the discrepancy could come from the different cross-section data utilized in the different Monte Carlo codes. In conclusion, the dosimetric functions for the new iodine seed InterSource(103) have been determined using the MCNP4B Monte Carlo code and TLD measurement in solid water WT1.