Treatment Of Cancer Guidelines Research Articles

Uncovering the Daily Experiences of People Living With Advanced Cancer Using an Experience Sampling Method Questionnaire: Development, Content Validation, and Optimization Study.

The experience sampling method (ESM), a self-report method that typically uses multiple assessments per day, can provide detailed knowledge of the daily experiences of people with cancer, potentially informing oncological care. The use of the ESM among people with advanced cancer is limited, and no validated ESM questionnaires have been developed specifically for oncology. This study aims to develop, content validate, and optimize the digital Experience Sampling Method for People Living With Advanced Cancer (ESM-AC) questionnaire, covering multidimensional domains and contextual factors. A 3-round mixed methods study was designed in accordance with the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) and the European Organization for Research and Treatment of Cancer guidelines. The study included semistructured interviews with 43 people with stage IV breast cancer or stage III to IV lung cancer and 8 health care professionals. Round 1 assessed the appropriateness, relative importance, relevance, and comprehensiveness of an initial set of ESM items that were developed based on the existing questionnaires. Round 2 tested the comprehensibility of ESM items. Round 3 tested the usability of the digital ESM-AC questionnaire using the m-Path app. Analyses included descriptive statistics and qualitative content analysis. Following the first round, we developed an initial core set of 68 items (to be used with all patients) and a supplementary set (optional; patients select items), both covering physical, psychological, social, spiritual-existential, and global well-being domains and concurrent contexts in which experiences occur. We categorized items to be assessed multiple times per day as momentary items (eg, "At this moment, I feel tired"), once a day in the morning as morning items (eg, "Last night, I slept well"), or once a day in the evening as evening items (eg, "Today, I felt hopeful"). We used participants' evaluations to optimize the questionnaire items, the digital app, and its onboarding manual. This resulted in the ESM-AC questionnaire, which comprised a digital core questionnaire containing 31 momentary items, 2 morning items, and 7 evening items and a supplementary set containing 39 items. Participants largely rated the digital questionnaire as "easy to use," with an average score of 4.5 (SD 0.5) on a scale from 1 ("completely disagree") to 5 ("completely agree"). We developed the ESM-AC questionnaire, a content-validated digital questionnaire for people with advanced breast or lung cancer. It showed good usability when administered on smartphone devices. Future research should evaluate the potential of this ESM tool to uncover daily experiences of people with advanced breast or lung cancer, explore its clinical utility, and extend its validation to other populations with advanced diseases.

Prophylactic pegfilgrastim to prevent febrile neutropenia among patients receiving biweekly (Q2W) chemotherapy regimens: a systematic review of efficacy, effectiveness and safety

BackgroundPegfilgrastim, a long-acting granulocyte colony-stimulating factor (G-CSF), is commonly used to prevent febrile neutropenia (FN), a potentially life-threatening complication, following myelosuppressive chemotherapy. The FDA label for pegfilgrastim specifies that it should not be administered 14 days before or within 24 h of administration of myelosuppressive chemotherapy, precluding the use of pegfilgrastim in biweekly (Q2W) regimens. The National Comprehensive Cancer Network and the European Organisation for Research and Treatment of Cancer guidelines support the use of prophylactic pegfilgrastim in patients receiving Q2W regimens. The objective of this study was to systematically review evidence from randomized clinical trials (RCTs) and observational studies that describe the effectiveness and safety of prophylactic pegfilgrastim in preventing FN among patients receiving Q2W regimens.MethodsAn Ovid MEDLINE, Embase, and Cochrane Library literature search was conducted to evaluate the evidence regarding efficacy, effectiveness, and safety of prophylactic pegfilgrastim versus no prophylactic pegfilgrastim or prophylaxis with other G-CSF in patients who were receiving Q2W chemotherapy regimens with high (> 20%) or intermediate (10–20%) risk of FN for a non-myeloid malignancy. Studies that addressed absolute or relative risk of FN, grade 1–4 neutropenia, all-cause or any hospitalization, dose delays or dose reductions, adverse events, or mortality were included. Studies where the comparator was a Q3W chemotherapy regimen with primary prophylactic pegfilgrastim were also included.ResultsThe initial literature search identified 2258 publications. Thirteen publications met the eligibility criteria, including eight retrospective, one prospective, one phase 1 dose escalation study, and three RCTs. In nine of the 13 studies reporting incidence of FN, and in seven of the nine studies reporting incidence of neutropenia, administration of prophylactic pegfilgrastim in patients receiving Q2W regimens resulted in decreased or comparable rates of FN or neutropenia compared with patients receiving filgrastim, no G-CSF, lipefilgrastim or pegfilgrastim in Q3W regimens. In six of the nine studies reporting safety data, lower or comparable safety profiles were observed between pegfilgrastim and comparators.ConclusionsIn a variety of non-myeloid malignancies, administration of prophylactic pegfilgrastim was efficacious in reducing the risk of FN in patients receiving high- or intermediate-risk Q2W regimens, with an acceptable safety profile.Trial registrationPROSPERO registration no: CRD42019155572.

Definition of fields margins for the optimized 2D radiotherapy of prostate carcinoma.

Prostate cancer (PCa) is one of the most common malignancies in men both in western and developing countries. Radiotherapy (RT) is an important therapeutic option. New technologies (including 3D, intensity modulated RT, image-guided RT and, volumetric modulated arc therapy) have been introduced in the last few decades with progressive improvement of clinical outcomes. However, in many developing countries, the only treatment option is the traditional two-dimensional (2D) technique based on standard simulation. The guidelines for 2D field definition are still based on expert's opinions. The aim of the present study was to propose new practical guidelines for 2D fields definition based on 3D simulation in PCa. A total of 20 patients were enrolled. Computed tomography-simulation and pelvic magnetic resonance images were merged to define the prostate volumes. Clinical Target Volume (CTV) was defined using the European Organisation for Research and Treatment of Cancer guidelines in consideration of the four risk categories: Low, intermediate, and high risk with or without seminal vesicles involvement, respectively. Planning Target Volume (PTV) was defined by adding 10 mm to the CTV. For each category, two treatment plans were calculated using a cobalt source or 10 MV photons. Progressive optimization was achieved by evaluating 3D dose distribution. Finally, the optimal distances between field margins and radiological landmarks (bones and rectum with contrast medium) were defined. The results were reported in tabular form. Both field margins (PTV D98% >95%) needed to adequately irradiate all patients and to achieve a similar result in 95% of the enrolled patients are reported. Using a group of patients with PCa and based on a 3D planning analysis, we propose new practical guidelines for PCa 2D-RT based on current criteria for risk category and CTV, and PTV definition.

Management of mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL): focus on chlormethine gel.

Mycosis fungoides (MF) is a low-grade cutaneous lymphoma accounting for more than half of primary cutaneous T-cell lymphomas (CTCLs). Due to the rarity of CTCL, randomized studies are lacking, and treatment is based mainly on the recent published European Organisation for Research and Treatment of Cancer guidelines. Basically, early-stage MF is treated with skin-directed treatments, whereas advanced-stage MF requires more aggressive therapies. Among the skin-directed therapies, nitrogen mustard has been used for more than 50 years. A gel formulation was developed recently, showing a slight decrease in efficacy, counterbalanced by better tolerance (essentially due to a decrease in delayed hypersensitivity reactions). This review aims to summarize the current management of MF and the role of chlormethine gel in the treatment of the disease.

Portuguese Version of the EORTC QLQ-OES18 and QLQ-OG25 for Health-Related Quality of Life Assessment.

Health-related quality of life assessment is increasingly important as it can help both clinical research and care forpatients, particularly among oncological patients. Quality of Life Questionnaire - OES18 (esophageal module) and Quality of LifeQuestionnaire - OG25 (esophagogastric module) are the European Organization for Research and Treatment of Cancer modules forthe evaluation of quality of life in patients with esophageal and esophagogastric cancers, respectively. The aim of our study was totranslate, to culturally adapt and to perform a pilot testing to create the Portuguese version of both questionnaires. The European Organization for Research and Treatment of Cancer guidelines were followed for translation,cultural adaptation and pilot testing of Quality of Life Questionnaire - OES18 (esophageal module) and Quality of Life Questionnaire- OG25 (esophagogastric module). The Quality of Life Questionnaire - OG25 (esophagogastric module) went through a process offorward (English → Portuguese) and backward (Portuguese → English) translation, by independent native speaker translators. Afterreview, a preliminary version was created to be pilot tested among Portuguese patients. As a Brazilian version was already availablefor Quality of Life Questionnaire - OES18 (esophageal module), the questionnaire was simply culturally adapted and pilot tested. Bothcancer and non-cancer patients were included. Overall, 30 patients completed the Portuguese version of each questionnaire. Afterwards, a structured interview wasconducted to find and report any problematic items. Troublesome items and wording were changed according to the pilot testing results.The final versions were sent to the European Organisation for Research and Treatment of Cancer Quality of Life Group and approved. The Portuguese versions of the European Organization for Research and Treatment of Cancer Quality of LifeQuestionnaire - OES18 (esophageal module) and OG25 (esophagogastric module) questionnaires are useful, reliable and valid toolsfor measuring health-related quality of life in patients with esophageal and esophagogastric cancers, respectively. They can now beused in clinical setting and for scientific purposes.

Norwegian translation, and validation, of the Pelvic Floor Distress Inventory (PFDI-20) and the Pelvic Floor Impact Questionnaire (PFIQ-7).

The goal was to translate into Norwegian, and validate, short versions of the Pelvic Floor Distress Inventory (PFDI-20) and the Pelvic Floor Impact Questionnaire (PFIQ-7) using a sample of women with symptomatic pelvic organ prolapse and pelvic floor dysfunction. Modified European Organization for Research and Treatment of Cancer Guidelines were used for translation and cultural adaptation. Of 212 eligible Norwegian women who consented to participate, 205 completed the questionnaires, of whom 50 were retested after 1-3weeks, and 76 were tested 6months after surgery. Reliability, validity and responsiveness were evaluated. Additionally, interpretability, the smallest detectable change, the standard error of measurement, floor and ceiling effects, and the percentages of missing items are reported. Reliability ranged from 0.66 to 0.93 and intraclass correlation coefficients from 0.85 to 0.94. Both construct validity and responsiveness were found to be adequate. The responsiveness of the PFDI-20 was further supported by areas under the curve above 0.70. Estimates were lower for the PFIQ-7. The smallest detectable changes at the individual level were 15-21% and 17-27% for the PFDI-20 and PFIQ-7, respectively. The absolute values of the minimal important changes in the total scores were 48 and 47, respectively. No floor or ceiling effects were evident in the distributions of the PFDI-20 and PFIQ-7 total scores. The translated questionnaires provided adequate reliability, validity and good responsiveness to change. These short versions of the PFDI and PFIQ are robust measuring instruments that will enable symptom severity and health-related quality of life to be evaluated in the Norwegian context.

PET/CT Response Criteria (European Organization for Research and Treatment of Cancer) Predict Survival Better Than Response Evaluation Criteria in Solid Tumors in Locally Advanced Cervical Cancer Treated With Chemoradiation

To investigate whether the ratio of SUVs measured with F-FDG PET/CT between pretreatment and posttreatment has prognostic value in patients with locally advanced cervical cancer treated with primary chemoradiation therapy. Cases of locally advanced cervical cancer (International Federation of Gynecology and Obstetrics stages IB1 to IVA) treated with a nonsurgical curative modality (172 cases including chemoradiation or radiation therapy) were reviewed. F-FDG PET/CT parameters, including SUVmax and SUVmean, were evaluated by F-FDG PET/CT performed prior to treatment and 6 weeks after the end of treatment. Metabolic response was evaluated according to the European Organization for Research and Treatment of Cancer guidelines and was compared with radiologic response measured according to the Response Evaluation Criteria In Solid Tumours (RECIST). In total, 142 patients receiving chemoradiation showed radiologic responses (median 56% decrease in maximal diameter), whereas 160 and 146 patients showed metabolic responses measured with SUVmax and SUVmean, respectively (73% decrease in SUVmax; 48% decrease in SUVmean). Radiologic response and metabolic response were significantly correlated for SUVmax and SUVmean (P = 0.0009; P = 0.0457, respectively). Kaplan-Meier analysis revealed significant differences in overall survival and progression-free survival between the responder and nonresponder groups, based on the European Organization for Research and Treatment of Cancer criteria (both P < 0.001), whereas no significant difference was found when using RECIST criteria (P = 0.058, P = 0.088, respectively). F-FDG PET/CT parameters are good prognostic markers for the response of cervical cancer patients to concurrent chemoradiation therapy, as compared with the RECIST criteria.

Validation of the German Version of the Quality of Dying and Death Questionnaire for Informal Caregivers (QODD-D-Ang)

ContextThe quality of dying and death (QOD) influences end-of-life care for patients and their relatives. To the best of our knowledge, there are currently no validated standard instruments for evaluating the QOD of patients in palliative care units (PCUs) in Germany. ObjectivesThis study aimed to validate the German version of the multidimensional questionnaire “Quality of Dying and Death” for informal caregivers (QODD-Deutsch-Angehörige [QODD-D-Ang]) and provide a detailed report on its validity and reliability. MethodsThe QODD was forward/backward translated following the European Organization for Research and Treatment of Cancer guidelines. Data collected in two German palliative care units (N = 226) with the QODD-D-Ang were used to calculate the QODD-D-Ang total score (TS) and to define reliability and validity, as well as acceptance and burden for informal caregivers. Frequencies, means, and SDs of various patient data related to care and disease were calculated to describe the study population and to look at group differences. ResultsThe mean TS of 175 participants was 75.72 (range 38–99; minimum 0 to maximum 100; higher scores indicate better QOD). The QODD-D-Ang showed good internal consistency for 27 items (Cronbach's alpha 0.852). Factors extracted by factor analysis could not be usefully interpreted. The TS of the QODD-D-Ang correlated substantially with the Palliative care Outcome Scale (r = 0.540), indicating good convergent validity. The QODD-D-Ang TS was stable for various demographic and clinical dimensions except for the amount of days on which informal caregivers visited patients, and, therefore, provided good discriminant validity. ConclusionAnalyses of validity and reliability of the QODD-D-Ang showed satisfactory to good psychometric properties, meaning that the QODD can be recommended for standard implementation in German hospices and palliative care institutions to measure the QOD. Feasibility could be improved by adapting the instrument so that it may be administered with minimal demands on staff. When interpreting the results, it should be kept in mind that the QODD-D-Ang does not measure quality of care but the quality of the dying process as estimated by bereaved relatives.

Use of EORTC Target Definition Guidelines for Dose-Intensified Salvage Radiation Therapy for Recurrent Prostate Cancer: Results of the Quality Assurance Program of the Randomized Trial SAKK 09/10

Different international target volume delineation guidelines exist and different treatment techniques are available for salvage radiation therapy (RT) for recurrent prostate cancer, but less is known regarding their respective applicability in clinical practice. A randomized phase III trial testing 64 Gy vs 70 Gy salvage RT was accompanied by an intense quality assurance program including a site-specific and study-specific questionnaire and a dummy run (DR). Target volume delineation was performed according to the European Organisation for the Research and Treatment of Cancer guidelines, and a DR-based treatment plan was established for 70 Gy. Major and minor protocol deviations were noted, interobserver agreement of delineated target contours was assessed, and dose-volume histogram (DVH) parameters of different treatment techniques were compared. Thirty European centers participated, 43% of which were using 3-dimensional conformal RT (3D-CRT), with the remaining centers using intensity modulated RT (IMRT) or volumetric modulated arc technique (VMAT). The first submitted version of the DR contained major deviations in 21 of 30 (70%) centers, mostly caused by inappropriately defined or lack of prostate bed (PB). All but 5 centers completed the DR successfully with their second submitted version. The interobserver agreement of the PB was moderate and was improved by the DR review, as indicated by an increased κ value (0.59 vs 0.55), mean sensitivity (0.64 vs 0.58), volume of total agreement (3.9 vs 3.3 cm(3)), and decrease in the union volume (79.3 vs 84.2 cm(3)). Rectal and bladder wall DVH parameters of IMRT and VMAT vs 3D-CRT plans were not significantly different. The interobserver agreement of PB delineation was moderate but was improved by the DR. Major deviations could be identified for the majority of centers. The DR has improved the acquaintance of the participating centers with the trial protocol.

Imaging for high-precision thoracic radiotherapy.

The motion of intra-thoracic tumors and radiosensitive normal organs is an important consideration when planning curative radiotherapy. An individualized assessment of such motion is preferable over use of standard 'planning margins', which may be based upon tumor location or patient characteristics (1-3). This is primarily because many tumors move less than 1 cm in any direction (3), thereby requiring smaller treatment fields. In addition, lung tumors may exhibit complex motions patterns, including hysteresis and be influenced by cardiac motion (4). Furthermore, patients with locally advanced lung cancer may exhibit motion in metastatic mediastinal nodes that exceeds that of the primary tumor or move maximally in a different phase (2,5). Identifying such variations in tumor motion can minimize the risk of compromising the effectiveness of radiotherapy delivery. Based on these studies, the European Organization for Research and Treatment of Cancer guidelines recommend use of respiration-correlateDCT or 4-Dimensional CT (4DCT) scans for planning (6).

Optimisation de la radiothérapie involved-node grâce à l’inspiration profonde bloquée dans la maladie de Hodgkin

PurposeTo assess the clinical outcome of the involved-node radiotherapy (INRT) concept with the use of deep-inspiration breath-hold (DIBH) technique in patients with localized supra-diaphragmatic Hodgkin lymphoma. Patients and methodsAll were patients with stage I–II Hodgkin lymphoma and they were treated with chemotherapy prior to irradiation. Radiation treatments were delivered using the involved-node radiotherapy concept according to the European Organization for Research and Treatment of Cancer Guidelines and a spirometer dedicated to DIBH radiotherapy was used for every patient. ResultsTwenty-seven patients with Hodgkin lymphoma (26 patients with primary Hodgkin lymphoma, one with refractory disease), treated from November 2004 to October 2010, were retrospectively analysed. The median age was 27 years (range 16 to 54). Seventeen (63%) patients had stage I–IIA and 10 (37%) had stage I–IIB disease. All patients received two to six cycles of adriamycin, bleomycin, vinblastine and dacarbazine. The median radiation dose to patients was 30,6Gy (range: 19,8–40). Protection of various organs at risk was satisfactory. Median follow-up, 3-year progression-free and 3-year overall survival were 38 months (range: 7–70), 96% (95%CI: 79–99%) and 95% (95%CI: 75–99%), respectively. Recurrence occurred in one patient (mediastinal in-field relapse). There was one grade 3 acute toxicity (transient pneumonitis). ConclusionsOur results suggest that patients with localized Hodgkin lymphoma can be safely and efficiently treated using deep-inspiration breath technique and the involved-node radiotherapy concept. Longer follow-up is needed to assess late toxicity, especially for the heart and the coronary arteries.

Consolidative Involved-Node Proton Therapy for Stage IA-IIIB Mediastinal Hodgkin Lymphoma: Preliminary Dosimetric Outcomes From a Phase II Study

To compare the dose reduction to organs at risk (OARs) with proton therapy (PT) versus three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) in patients with mediastinal Hodgkin lymphoma (HL) enrolled on a Phase II study of involved-node radiotherapy (INRT). Between June 2009 and October 2010, 10 patients were enrolled on a University of Florida institutional review board-approved protocol for de novo "classical" Stage IA-IIIB HL with mediastinal (bulky or nonbulky) involvement after chemotherapy. INRT was planned per European Organization for Research and Treatment of Cancer guidelines. Three separate optimized plans were developed for each patient: 3D-CRT, IMRT, and PT. The primary end point was a 50% reduction in the body V4 with PT compared with 3D-CRT or IMRT. The median relative reduction with PT in the primary end point, body V4, was 51% compared with 3D-CRT (p = 0.0098) and 59% compared with IMRT (p = 0.0020), thus all patients were offered treatment with PT. PT provided the lowest mean dose to the heart, lungs, and breasts for all 10 patients compared with either 3D-CRT or IMRT. The median difference in the OAR mean dose reduction with PT compared with 3D-CRT were 10.4 Gy/CGE for heart; 5.5Gy/CGE for lung; 0.9 Gy/CGE for breast; 8.3 Gy/CGE for esophagus; and 4.1 Gy/CGE for thyroid. The median differences for mean OAR dose reduction for PT compared with IMRT were 4.3 Gy/CGE for heart, 3.1 Gy/CGE for lung, 1.4 Gy/CGE for breast, 2.8 Gy/CGE for esophagus, and 2.7 Gy/CGE for thyroid. All 10 patients benefitted from dose reductions to OARs with PT compared with either 3D-CRT or IMRT. It is anticipated that these reductions in dose to OAR will translate into lower rates of late complications, but long-term follow-up on this Phase II INRT study is needed.

Involved-Node Radiotherapy and Modern Radiation Treatment Techniques in Patients With Hodgkin Lymphoma

To assess the clinical outcome of the involved-node radiotherapy (INRT) concept using modern radiation treatments (intensity-modulated radiotherapy [IMRT] or deep-inspiration breath-hold radiotherapy [DIBH) in patients with localized supradiaphragmatic Hodgkin lymphoma. All but 2 patients had early-stage Hodgkin lymphoma, and they were treated with chemotherapy prior to irradiation. Radiation treatments were delivered using the INRT concept according to European Organization for Research and Treatment of Cancer guidelines. IMRT was performed with the patient free-breathing. For the adapted breath-hold technique, a spirometer dedicated to DIBH radiotherapy was used. Three-dimensional conformal radiotherapy was performed with those patients. Fifty patients with Hodgkin lymphoma (48 patients with primary Hodgkin lymphoma, 1 patient with recurrent disease, and 1 patient with refractory disease) entered the study from January 2003 to August 2008. Thirty-two patients were treated with IMRT, and 18 patients were treated with the DIBH technique. The median age was 28 years (range, 17-62 years). Thirty-four (68%) patients had stage I - (I-IIA) IIA disease, and 16 (32%) patients had stage I - (I-IIB) IIB disease. All but 3 patients received three to six cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). The median radiation doses to patients treated with IMRT and DIBH were, respectively, 40 Gy (range, 21.6-40 Gy) and 30.6 Gy (range, 19.8-40 Gy). Protection of various organs at risk was satisfactory. Median follow-up was 53.4 months (range, 19.1-93 months). The 5-year progression-free and overall survival rates for the whole population were 92% (95% confidence interval [CI], 80%-97%) and 94% (95% CI, 75%-98%), respectively. Recurrences occurred in 4 patients: 2 patients had in-field relapses, and 2 patients had visceral recurrences. Grade 3 acute lung toxicity (transient pneumonitis) occurred in 1 case. Our results suggest that patients with localized Hodgkin lymphoma can be safely and efficiently treated using the INRT concept and modern radiation treatment techniques such as IMRT and DIBH.

Rectal Filling at Planning Does Not Predict Stability of the Prostate Gland during a Course of Radical Radiotherapy if Patients with Large Rectal Filling are Re-imaged

Aims It has been suggested that large rectal filling is associated with an increased risk of prostate motion in radiotherapy. The aim of the present study was to determine if there is a correlation between rectal distension on planning computed tomography and the intrafraction and interfraction stability of the prostate gland during a course of radical radiotherapy for prostate cancer if a protocol was used to rescan patients with excessive rectal diameter during planning. Materials and methods The computed tomography planning scans of 89 patients with adenocarcinoma of the prostate treated with conformal radiotherapy were reviewed. All patients had three gold seed fiducial markers implanted into the prostate before planning computed tomography. About one in five patients had repeat computed tomography because their rectum was judged to be too large at the time of the first planning computed tomography. Rectal distension was assessed on planning computed tomography using outlines following European Organization for Research and Treatment of Cancer guidelines by measuring the rectal volume, the average cross-sectional area and the mean anterior–posterior diameter of the rectum. Daily kV images were obtained before and after treatment delivery to determine positional matching of the fiducial markers in the superior–inferior, anterior–posterior and right–left dimensions. Results In total, 2860 pre- and post-treatment daily kV image pairs were obtained of 89 patients (average 32.1 image pairs per patient). The median rectal cross-sectional area was 7.3 cm 2 (range 2.8–17.1), the median rectal volume was 54.8 cm 3 (range 20.9–128.2), and the median anterior–posterior rectal diameter was 3.03 cm (range 1.58–8.30). Unifactor linear regression models showed no statistically significant relationship between intra- and interfraction prostate stability and rectal volume on planning computed tomography. Conclusions No statistically significant relationship between rectal distension on planning computed tomography and the intra- and interfraction stability of the prostate gland was identified if patients with a large rectal volume were rescanned for planning.

The economic value of primary prophylaxis using pegfilgrastim compared with filgrastim in patients with breast cancer in the UK

Febrile neutropenia (FN) is a serious adverse event associated with myelotoxic chemotherapy that predisposes patients to life-threatening bacterial infections. Prophylaxis with granulocyte colony-stimulating factors (G-CSFs) from the first cycle of chemotherapy is recommended by the 2006 American Society of Clinical Oncology, 2008 National Comprehensive Cancer Network and 2006 European Organisation for Research and Treatment of Cancer guidelines when the overall risk of FN is approximately 20% or higher. Once-per-cycle pegfilgrastim and daily filgrastim are two commonly used G-CSFs with different dosing schedules and associated costs. To evaluate the cost effectiveness of pegfilgrastim versus filgrastim primary prophylaxis in women with early-stage breast cancer receiving chemotherapy in the UK. A decision-analytic model was constructed from the UK NHS perspective with a lifetime study horizon. The model simulated three clinical scenarios: scenario 1 assumed that pegfilgrastim and filgrastim had differential impact on the risk of FN; scenario 2 assumed additional differential impact on FN-related mortality; and scenario 3 assumed additional differential impact on chemotherapy relative dose intensity (RDI) with long-term survival effects. The base-case population included 45-year-old women with stage II breast cancer receiving four chemotherapy cycles, with an FN risk of approximately 20% or higher. Model inputs, including FN risk, FN case-fatality, RDI, impact of RDI on survival and utility scores, were based on a review of the literature and expert panel validation. Using data from the literature, it was estimated that the absolute risk of FN associated with pegfilgrastim was 5.5% lower than with 11-day filgrastim (7% vs 12.5%), and 10.5% lower than with 6-day filgrastim (7% vs 17.5%). Costs were taken from official price lists or the literature and included drugs, drug administration, FN-related hospitalizations and subsequent medical costs. Breast cancer mortality and all-cause mortality were obtained from official statistics. The main outcome measures were the costs ( pound, year 2006 values) per percentage decrease in (absolute) FN risk, per FN event avoided, per life-year gained (LYG), and per QALY gained. Model robustness was tested using deterministic and probabilistic sensitivity analyses. Pegfilgrastim was cost saving compared with 11-day filgrastim ( pound 3196 vs pound 4315). Compared with 6-day filgrastim, pegfilgrastim was associated with a cost of pound 4200 per FN event avoided, or pound 42 per 1% decrease in absolute risk of FN, in scenario 1. In scenario 2, pegfilgrastim provided 0.055 more LYGs or 0.052 more QALYs at a minimal cost increase of pound 441 ( pound 3196 vs pound 2754) per person, yielding an incremental cost-effectiveness ratio (ICER) of pound 8075/LYG or pound 8526/QALY. In scenario 3, when all potential benefits of G-CSF were considered, the ICER became pound 3955/LYG or pound 4161/QALY. Results were most sensitive to the relative risk of FN for 6-day filgrastim versus pegfilgrastim. In this UK analysis, pegfilgrastim appears to dominate 11-day use of filgrastim. The value of pegfilgrastim versus 6-day filgrastim at pound 4161-8526/QALY was very favourable compared with the commonly used threshold in the UK. In this setting, primary prophylaxis with pegfilgrastim may be cost effective compared with filgrastim.

The impact of new European Organisation for Research and Treatment of Cancer guidelines on the use of granulocyte colony-stimulating factor on the management of breast cancer patients

Febrile neutropenia (FN) is a severe consequence of myelosuppressive therapy. The European Organisation for Research and Treatment of Cancer recently published guidelines on the use of granulocyte colony-stimulating factor (G-CSF) to prevent FN in patients with malignant disease. In this review, the impact of these guidelines on breast cancer treatment is discussed. A brief summary of FN in breast cancer is given, and patient-related and treatment schedule-related risk factors for FN are reviewed for the adjuvant/neoadjuvant and metastatic disease settings. Primary G-CSF support is recommended if the overall FN risk is ⩾20%, or if a reduction in dose-intensity is associated with a poorer outcome. Any formulation of G-CSF is recommended. The utility of G-CSF in reducing the incidence of FN and enabling treatment regimens is discussed.

Effect of Treatment with Epoetin Beta on Thromboembolic Events in Anemic Patients with Cancer: A Metaanalysis

PurposeEpoetin therapy is associated with a slight increase in thromboembolic event (TEE) incidence, although causality is uncertain. This metaanalysis compared TEE incidence in patients with cancer-related anemia treated with epoetin beta versus a control group (placebo or standard treatment) and investigated the impact of hemoglobin (Hb) parameters on thromboembolic risk. Patients and MethodsPatients from 9 randomized trials were pooled (epoetin beta group, n = 800; control group, n = 613). Adverse event reports were reviewed for all TEEs recorded during treatment and 28 days thereafter. Thromboembolic event incidence was compared between 2 groups, and standard statistical analyses were conducted to investigate the potential of Hb parameters to modulate thromboembolic risk. ResultsFor epoetin beta, 5.9% of patients (n = 47) experienced ≥ 1 TEE versus 4.2% of controls (n = 26; not significant). Thromboembolic-related mortality rates were 1% in both groups. Thromboembolic event rates in patients stratified by tumor type were consistent with the overall population. For epoetin beta, greater baseline-adjusted Hb area under the concentration-time curve and greater Hb increases during the first 4 weeks of treatment significantly correlated with reduced risk of TEEs. Conversely, treatment in those with higher baseline Hb levels was associated with increased TEE risk. ConclusionWhen administered in accordance with European Organization for Research and Treatment of Cancer guidelines, epoetin beta did not appear to be associated with increased thromboembolic risk. Although risk of TEEs might be marginally increased in patients with cancer treated with epoetin beta, there is no increased risk of thromboembolic mortality.