Precision oncology medicines and the need for real world evidence acceptance in health technology assessment: Importance of patient involvement in sustainable healthcare.

Precision oncology has made remarkable strides in improving clinical outcomes, offering hope to patients with historically difficult-to-treat, as well as rare or neglected cancers. However, despite rapid advancement, precision oncology has reached a critical juncture, where patient access to these life-saving medicines may be hampered by strict requirements by Health Technology Assessment (HTA) bodies for randomised controlled trials (RCTs) for assessing new medicines against appropriate comparator. The very nature of precision oncology-matching a tumour's unique molecular alterations to targeted therapies predicted to elicit response-can make the use of RCTs very difficult, as only a very small number of patients might qualify for a given therapy within a traditional clinical trial setting. Real-world evidence (RWE) has been accepted for regulatory decision-making but has yet to reach widespread acceptance by HTA bodies. As the oncology treatment landscape has evolved towards favouring the concept of precision oncology, there is a growing need for flexibility in the way HTA bodies evaluate new medicines. We must acknowledge that current assessment methodologies can limit access to life-changing medicines for many patients who have no alternative options and that a growing number of precision oncology medicines with proven clinical benefits in rare tumours cannot be reasonably evaluated using traditional methodologies. The objectives of this paper are to advocate a change in mindset regarding best practices in drug assessment models and to propose alternative approaches when considering indications for which RWE is the most compelling data source available.

Comparison of Alternative Methods to Assess the Cost-Effectiveness of Tumor-Agnostic Therapies: A Triangulation Approach Using Larotrectinib as a Case Study.

OBJECTIVES: The study objective was to investigate the economic value of tumor-agnostic therapies when only single-arm effectiveness data are available at launch by applying multiple methodologies to establish comparative effectiveness. METHODS: In the absence of direct comparative data, 3 methods were used to estimate the counterfactual: (1) a historical control based on a systematic literature review for each tumor site from the larotrectinib trials, (2) an intracohort comparison using the previous line of therapy time to progression from larotrectinib trials, and (3) a nonresponder control that applied outcomes for larotrectinib nonresponders. Cost-effectiveness was modeled using the partitioned survival approach. Stochastic parameter uncertainty was assessed in a probabilistic sensitivity analysis (PSA). A triangulated estimate of the mean cost-effectiveness result was generated combining all 3 counterfactual estimates. RESULTS: Incremental cost-effectiveness ratios were similar across the 3 methodologies in the deterministic analysis ranging from £83 868 (95% uncertainty interval [UI] £65 698-£107 668) to £104 922 per quality-adjusted life-year (95% UI £80 132-£139 658). PSA results for each method substantially overlapped when plotted on the cost-effectiveness plane. Weighting PSA results for each method equally in the triangulation method produced an incremental cost-effectiveness ratios of £95 587 per quality-adjusted life-year gained (95% UI £70 449-£137 431). CONCLUSIONS: In the absence of direct comparative data, different methods of estimating a counterfactual are possible, each with strengths and limitations. Triangulating results across the methods provides a composite view of the total uncertainty and a more consistent estimation of the cost-effectiveness of the tumor-agnostic intervention compared with choosing a single method.

Patient assessment and feasibility of treatment in older patients with cancer: results from the IN-GHO® Registry.

PURPOSE: Predicting feasibility of treatment in older patients with cancer is a major clinical task. The Initiative Geriatrische Hämatologie und Onkologie (IN-GHO®) registry prospectively collected data on the comprehensive geriatric assessment (CGA), physician's and patient's-self assessment of fitness for treatment, and the course of treatment in patients within a treatment decision aged ≥ 70 years. PATIENTS AND METHODS: The registry included 3169 patients from 93 centres and evaluated clinical course and treatment outcomes 2-3 and 6 months after initial assessment. Fitness for treatment was classified as fit, compromised and frail according to results of a CGA, and in addition by an experienced physician's and by patient's itself. Feasibility of treatment (termed IN-GHO®-FIT) was defined as a composite endpoint, including willingness to undergo the same treatment again in retrospect, no modification or unplanned termination of treatment, and no early mortality (within 90 days). RESULTS: CGA classified 30.0% as fit, 35.8% as compromised, and 34.2% as frail. Physician's and patient's-self assessment classified 61.8%/52.3% as fit, 34.2%/42.4% as compromised, and 3.9%/5.3%, as frail, respectively. Survival status at day 180 was available in 2072 patients, of which 625 (30.2%) had died. After 2-3 months, feasibility of treatment could be assessed in 1984 patients. 62.8% fulfilled IN-GHO®-FIT criteria. Multivariable analysis identified physician's assessment as the single most important item regarding feasibility of treatment. CONCLUSION: Geriatricians were involved in 2% of patients only. Classification of fitness for treatment by CGA, and physician's or patient's-self assessment showed marked discrepancies. For the prediction of feasibility of treatment no single item was superior to physician's assessment. However CGA was not performed by trained geriatricians.

Developing a Framework for the Health Technology Assessment of Histology-independent Precision Oncology Therapies.

The arrival of precision oncology is challenging the evidence standards under which technologies are evaluated for regulatory approval as well as for health technology assessment (HTA) purposes. Several key concepts are discussed to highlight the source of the challenges in evaluating these products, particularly those impacting the HTA of histology-independent therapies. These include the basket trial design, high uncertainty in (potentially substantial) benefits for histology-independent therapies, and the inability to identify and quantify benefits of standard of care in daily practice when the biomarker is not currently used in practice. There is little precedent for a technology with the unique mixture of challenges for HTA of histology-independent therapies and they will be evaluated using standard HTA, as there currently is no evidence suggesting the standard HTA framework is not appropriate. A number of questions proposed to help guide HTA bodies when assessing the appropriateness of local processes to optimally evaluate histology-independent therapies. Pragmatic solutions are further proposed to decrease uncertainty in the benefits of histology independent therapies as well as fill gaps in comparative evidence. The proposed solutions ensure a consistent and streamlined approach to evaluation across histology-independent products, although with varying strengths and limitations. Alongside these solutions, sponsors should engage early with HTA bodies/payers and regulatory agencies through parallel/joint scientific advice to facilitate the integration of both regulatory and HTA perspectives into one clinical development programme, potentially reconciling evidence requirements.

Management of Germ Cell Tumours of the Testis in Adult Patients. German Clinical Practice Guideline Part I: Epidemiology, Classification, Diagnosis, Prognosis, Fertility Preservation, and Treatment Recommendations for Localized Stages.

INTRODUCTION: This is the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up on germ cell tumours (GCTs) of the testis in adult patients. We present the guideline content in two publications. Part I covers the topic's background, methods, epidemiology, classification systems, diagnostics, prognosis, and treatment recommendations for the localized stages. METHODS: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search was in March 2018) were provided. Thirty-one experts entitled to vote, rated the final clinical recommendations and statements. RESULTS: We provide 161 clinical recommendations and statements. We present information on the quality of cancer care and epidemiology and give recommendations for staging and classification as well as for diagnostic procedures. The diagnostic recommendations encompass measures for assessing the primary tumour as well as procedures for the detection of metastases. One chapter addresses prognostic factors. In part I, we separately present the treatment recommendations for germ cell neoplasia in situ, and the organ-confined stages (clinical stage I) of both seminoma and nonseminoma. CONCLUSION: Although GCT is a rare tumour entity with excellent survival rates for the localized stages, its management requires an interdisciplinary approach, including several clinical experts. Quality of care is highly related to institutional expertise and can be reassured by established online-based second-opinion boards. There are very few studies on diagnostics with good level of evidence. Treatment of metastatic GCTs must be tailored to the risk according to the International Germ Cell Cancer Collaboration Group classification after careful diagnostic evaluation. An interdisciplinary approach as well as the referral of selected patients to centres with proven experience can help achieve favourable clinical outcomes.

Comparison of acetylsalicylic acid and clopidogrel non-responsiveness assessed by light transmittance aggregometry and PFA-100® in patients undergoing neuroendovascular procedures.

Objectives: Dual platelet inhibition is commonly used for prevention of cardiovascular events in patients undergoing neuroendovascular procedures. Non-responsiveness to platelet inhibitors may be associated with adverse outcomes. The aim of this study was to evaluate the reliability of the platelet function analyzer PFA-100® in comparison to light transmittance aggregometry (LTA) for monitoring clopidogrel and acetylsalicylic acid (ASA) non-responsiveness in a cohort of patients treated for intracranial aneurysm or cranial artery stenosis. Methods: Non-responsiveness to clopidogrel and ASA was assessed by LTA using adenosine diphosphate (ADP) and arachidonic acid and by PFA-100® with the ADP/prostaglandin E1 (PGE1) and collagen/epinephrine cartridges, respectively. Results: A total of 203 patients (145 females; median age, 57 years) were analyzed. Agreement between the two tests was poor for clopidogrel non-responsiveness (ƙ=0.19) and not better than chance for ASA non-responsiveness (ƙ=0.01). Clopidogrel non-responsiveness by LTA and PFA-100® was associated with higher von Willebrand factor antigen and activity levels. ADP-induced platelet disaggregation was lower in patients with clopidogrel non-responsiveness as assessed by PFA-100®. Clopidogrel non-responsiveness by LTA was associated with a higher prevalence of diabetes and a higher body mass index (BMI). Adverse outcomes (death, thromboembolism, or in-stent thrombosis) occurred in 13% (n=26) of all patients independently of ASA and clopidogrel non-responsiveness as assessed by both devices. Conclusions: Our results show that LTA and PFA-100® are not interchangeable in the assessment of ASA and clopidogrel non-responsiveness in patients undergoing neuroendovascular interventions.

Individual specialist physical activity assessment and intervention in advanced cancer patients on a palliative care ward; the 3STEPS-study.

The aim of this prospective study was to evaluate the feasibility and outcome of an activity assessment and intervention on a specialized palliative care ward. All patients admitted between May 2017 and April 2018 were screened for basic assessment (Step 1). Whenever possible the Tinetti-mobility test (TT) was performed by a physiotherapist. A comparison between physician and nurse-led assessment and patient report was performed (Step 2), followed by a low-intensity individually adapted activity intervention (Step 3). Physical function and global quality of life was measured at intervention start and at discharge. Home care training adherence was controlled by phone call. In total, 437 patients were admitted in one year. In 248 patients, a basic assessment was done of which 131 performed a TT. In this group, median age was 63 years. Types of cancer were gastrointestinal (n=39), lung (n=27), urogenital (n=20), non-cancer (n=26) and other (n=26). Median length of stay was 13 days. Correlations between assessment methods were low to moderate, the highest between the TT and the nurse led assessment. Six patients started the intervention. Four patients completed the intervention, of which two continued with the home based training. In all four patients, an improvement in outcomes was measured. In conclusion in around a quarter of patients on a palliative care ward a TT could be performed. The TT correlated to most with nurse led mobility assessment. In the few accrued patients, the activity intervention showed an effect.

Systematic symptom and problem assessment at admission to the palliative care ward - perspectives and prognostic impacts.

BACKGROUND: Symptom assessment is essential in palliative care, but holds challenges concerning implementation and relevance. This study aims to evaluate patients' main symptoms and problems at admission to a specialist inpatient palliative care (SIPC) ward using physician proxy- and patient self-assessment, and aims to identify their prognostic impact as well as the agreement between both assessments. METHODS: Within 12 h after admission, palliative care specialists completed the Symptom and Problem Checklist of the German Hospice and Palliative Care Evaluation (HOPE-SP-CL). Patients either used the new version of the minimal documentation system for patients in palliative care (MIDOS) or the Integrated Palliative Care Outcome Scale (IPOS) plus the Distress Thermometer (DT). RESULTS: Between 01.01.2016-30.09.2018, 1206 patients were included (HOPE-SP-CL 98%; MIDOS 21%, IPOS 34%, DT 27%) whereof 59% died on the ward. Proxy-assessment showed a mean HOPE-SP-CL Total Score of 24.6 ± 5.9 of 45. Most frequent symptoms/problems of at least moderate intensity were weakness (95%), needs of assistance with activities of daily living (88%), overburdening of family caregivers (83%), and tiredness (75%). Factor analysis identified four symptom clusters (SCs): (1) Deteriorated Physical Condition/Decompensation of Home Care, (2) Emotional Problems, (3) Gastrointestinal Symptoms and (4) Other Symptoms. Self-assessment showed a mean MIDOS Total Score of 11.3 ± 5.3 of 30, a mean IPOS Total Score of 32.0 ± 9.0 of 68, and a mean distress of 6.6 ± 2.5 of 10. Agreement of self- and proxy-assessment was moderate for pain (ƙ = 0.438) and dyspnea (ƙ = 0.503), fair for other physical (ƙ = 0.297 to 0.394) and poor for psychological symptoms (ƙ = 0.101 to 0.202). Multivariate regression analyses for single symptoms and SCs revealed that predictors for dying on the SIPC ward included impaired ECOG performance status, moderate/severe dyspnea, appetite loss, tiredness, disorientation/confusion, and the SC Deteriorated Physical Condition/Decompensation of Home Care. CONCLUSION: Admissions to a SIPC ward are mainly caused by problems impairing mobility and autonomy. Results demonstrate that implementation of self- and reliability of proxy- and self-assessment is challenging, especially concerning non-physical symptoms/problems. We identified, specific symptoms and problems that might provide information needed for treatment discussions regarding the medical prognosis.

Implications of SARS-CoV-2 Infection and COVID-19 Crisis on Clinical Cancer Care: Report of the University Cancer Center Hamburg.

With the outbreak of the COVID-19 pandemia, routine clinical work was immediately, deeply, and sustainably impacted in Germany and worldwide. The infrastructure of almost all hospitals is currently redirected to provide a maximum of intensive care resources, including the necessary staff. In parallel, routine as well as emergency clinical care for all patients in need has to be secured. This challenge becomes particularly evident in cancer care. In order to maintain adequate oncological care at all levels of provision and to conduct especially curative and intensive treatments with a maximum of safety, continuous adaption of the oncology care system has to be ensured. Intensive communication with colleagues and patients is needed as is consequent expert networking and continuous reflection of the own developed strategies. In parallel, it is of high importance to actively avoid cessation of innovation in order not to endanger the continuous improvement in prognosis of cancer patients. This includes sustained conduction of clinical trials as well as ongoing translational research. Here, we describe measures taken at the University Cancer Center Hamburg (UCCH) - a recognized comprehensive oncology center of excellence - during the COVID-19 crisis. We aim to provide support and potential perspectives to generate a discussion basis on how to maintain high-end cancer care during such a crisis and how to conduct patients safely into the future.

Exploring the gender dimension of problems and needs of patients receiving specialist palliative care in a German palliative care unit - the perspectives of patients and healthcare professionals.

BACKGROUND: Gender disparities of specific symptoms and problems have frequently been observed in palliative care patients, but research rarely focused on the range of problems and needs affected by gender. METHODS: We conducted semi-structured interviews with patients and healthcare professionals (HCPs) of a hospital-based palliative care unit to examine gender effects on patients' problems and needs based on systematically gathered qualitative data. Content analysis was used to identify emerging themes with data coded using MAXQDA. RESULTS: Ten patients (5 female, 5 male) and 17 HCPs (12 female, 5 male) were interviewed. Seven categories of gender-specific problems and needs emerged: "physical symptoms, care and body image", "psychological symptoms and emotional response", "interaction with the palliative care team", "use of professional supportive measures", "activation of informal social networks", "decision-making", and "preservation of autonomy and identity". Both patients and HCPs felt that female patients adopt more expressive coping strategies, have stronger need for communication with and support of HCPs, and activate an extended social network for support and decision-making. Further, both groups thought that male patients mainly rely on social support from partners, have higher expectations to be cared for at home, and have higher need for preservation of autonomy. CONCLUSION: Gender relevantly impacts patients' problems and needs during palliative care. Therefore, gender-sensitive palliative care that acknowledges the patient's individual situation and respective ramifications are required.

Specific Characteristics of Patients with Advanced Genitourinary Cancer Receiving Specialized Inpatient Palliative Care.

BACKGROUND: The aim of this study was to compare the characteristics for genitourinary cancer (GUC) patients receiving specialized inpatient palliative care (SIPC) with those of a general cohort. METHODS: We retrospectively evaluated 151 GUC patients receiving SIPC from 2008 to 2014 regarding symptoms, problems, treatment, and outcome. These characteristics were compared with a general cohort of 1,285 patients with various diseases who received SIPC (German Hospice and Palliative care investigation: HOPE). RESULTS: Patients suffering from advanced prostate cancer (n = 59), renal cell cancer (n = 37), urothelial cancer (n = 36), urothelial accompanied by prostate cancer (n = 11), germ cell cancer (n = 7), and penile squamous cell cancer (n = 1) were included in the study. Most frequent symptoms and problems at admission were weakness (93%), the need for assistance with activities of daily living (85%), loss of appetite (81%), and organization of care (80%). Symptoms were more frequent in the GUC than in the general cohort during treatment, in particular with regards to pain (p < 0.001), tension (p < 0.001), nausea (p = 0.001), and vomiting (p < 0.001). GUC patients received significantly more opioids with 89% compared to the general cohort with 72% (p < 0.001). CONCLUSION: Symptom burden of GUC patients, in particular pain, tension, and nausea was higher compared to the general cohort, and analgesic treatment played an important role in achieving control of symptoms.

Quality of life, psychological burden, needs, and satisfaction during specialized inpatient palliative care in family caregivers of advanced cancer patients.

BACKGROUND: This pilot study aimed to investigate quality of life, psychological burden, unmet needs, and care satisfaction in family caregivers of advanced cancer patients (FCs) during specialized inpatient palliative care (SIPC) and to test feasibility and acceptance of the questionnaire survey. METHODS: During a period of 12 weeks, FCs were recruited consecutively within 72 h after the patient's admission. They completed validated scales on several outcomes: quality of life (SF-8), distress (DT), anxiety (GAD-7), depression (PHQ-9), supportive needs (FIN), palliative care outcome (POS), and satisfaction with care (FAMCARE-2). We used non-parametric tests, t-tests and correlation analyses to address our research questions. RESULTS: FCs showed high study commitment: 74 FCs were asked to participate whereof 54 (73%) agreed and 51 (69%) returned the questionnaire. Except for "bodily pain", FCs' quality of life (SF-8) was impaired in all subscales. Most FCs (96%) reported clinically significant own distress (DT), with sadness, sorrows and exhaustion being the most distressing problems (80-83%). Moderate to severe anxiety (GAD-7) and depression (PHQ-9) were prevalent in 43% and 41% of FCs, respectively. FCs scored a mean number of 16.3 of 20 needs (FIN) as very or extremely important (SD 3.3), 20% of needs were unmet in >50% of FCs. The mean POS score assessed by FCs was 16.6 (SD 5.0) and satisfaction (FAMCARE-2) was high (73.4; SD 8.3). CONCLUSIONS: This pilot study demonstrated feasibility of the questionnaire survey and showed relevant psychosocial burden and unmet needs in FCs during SIPC. However, FCs' satisfaction with SIPC seemed to be high. A current multicenter study evaluates these findings longitudinally in a large cohort of FCs.

Anxiety and fear of cancer recurrence and its association with supportive care needs and health-care service utilization in cancer patients.

PURPOSE AND METHODS: We investigated the relationship between fear of cancer recurrence (FCR), anxiety, supportive care needs, and utilization of health-care services in a mixed sample of 335 cancer patients. We used validated questionnaires including the Fear of Progression Questionnaire-Short Form (FoP-Q-SF), the General Anxiety Disorder Scale (GAD-7) and the Supportive Care Needs Survey (SCNS-SF34). Health-care services utilization was measured by a self-constructed questionnaire recording the use of 22 health and supportive care offers. RESULTS: In our sample, 3.9% of patients were classified as having high anxiety and 5.1% had high FCR. Patients reported the highest unmet supportive care needs in the domain health system and information followed by psychological needs. Integrated care and complementary support services were the most frequently used (32%) followed by medical (31%), psychological (23%), spiritual and religious (8%) and other support services (9%). Whereas anxiety was related to both unmet psychological and physical/daily living needs (p < 0.01), FCR was associated with unmet supportive care needs in all five domains further including needs with regard to health system and information, patient care, and sexuality (p < 0.01). However, higher levels of anxiety and FCR were not related to higher utilization of health-care services. CONCLUSION: Our findings show that FCR plays a significant role in unmet supportive care needs in cancer patients but not for health-care service utilization. IMPLICATIONS FOR CANCER SURVIVORS: We recommend that clinicians monitor supportive care needs in patients struggling with FCR and anxiety.

Reducing the burden of bone metastases: current concepts and treatment options.

BACKGROUND: Bone metastases occur frequently in patients with solid tumours such as those of the prostate, breast and lung, and are associated with an increased risk of skeletal-related events (SREs). This article reviews the personal, social and economic burdens of bone metastases and SREs, and approaches to treatment. METHODS: PubMed searches were conducted using a broad range of search terms. Articles identified were refined by author review of abstracts. Additional material was identified by searching recent relevant congress abstracts. RESULTS: Bone metastases often decrease quality of life, but quantitative data on the extent of this effect are limited. Data from the USA demonstrate a significant financial burden associated with bone metastases; similar trends are now being uncovered in Europe as the number of assessments of health economics and healthcare resource utilisation in the region increases. The bisphosphonate zoledronic acid reduces the incidence of SREs compared with placebo. Recent phase 3 studies have shown that therapy with the RANK ligand inhibitor denosumab is superior to zoledronic acid for preventing or delaying SREs in patients with bone metastases from solid tumours. Denosumab also has a comparable safety profile to bisphosphonates, with reduced risk of renal toxicity and acute phase reactions. Data from Europe suggest that denosumab is cost-effective for the prevention of SREs compared with zoledronic acid. Additionally, several new experimental bone-targeted agents show promise. CONCLUSION: Recent progress may help to reshape evidence-based guidelines to improve patient care and reduce the economic burden of bone metastases.

Symptom burden in palliative care patients: perspectives of patients, their family caregivers, and their attending physicians.

RATIONALE: The purpose of this study was to prospectively evaluate the perspectives of palliative care patients, their family caregivers, and their attending palliative care specialists on frequency, intensity, distress, and treatment requirement of the patient's physical and psychological symptoms. PATIENTS AND METHODS: Forty advanced cancer patients and their family caregivers were recruited through a palliative care inpatient ward within 24 h after admission. Patients, caregivers, and physicians completed a modified version of the Memorial Symptom Assessment Scale (including perceived treatment requirement). RESULTS: Thirty-nine patients (98 %) suffered from at least one symptom frequently or almost constantly (median number 5; range, 0-9). Most frequent symptoms were lack of energy (95 %), tiredness (88 %), and pain (80 %), which were scored correspondingly by patients, caregivers, and physicians to be the most intensive, distressing, and treatment requiring. Treatment requirement was determined by symptom intensity or distress in patients and physicians, but by distress in caregivers. Significant differences in symptom burden between patients, caregivers, and physicians were found with regard to pain (p = .007), tiredness (p = .037), lack of energy (p < .05), anxiety (p < .05), and sadness (p < .05). Physicians underestimated 60 % of symptom dimensions, while the caregivers overestimated 77 %; however, overall median scoring differences were limited with -.10 (range, -.55 to +.25) between patients and physicians and +.33 (range, -.78 to +.61) between patients and family caregivers. CONCLUSIONS: While physicians tended to underestimate, family caregivers tended to overestimate the patient's symptoms. Therefore, adequate symptom treatment can only be successful in a close dialog between patients, their caregivers, and a multidisciplinary team.

[Registries and clinical trials in geriatric oncology in Germany]. / Register und studienaktivitaten in der geriatrischen onkologie.

Regardless of the fact that elderly cancer patients in Germany are more and more recognized as a cohort with special characteristics and potentially specific needs, there is a lack of sound data from clinical trials that could guide the care of this population. This article addresses the issue of underrepresentation of elderly patients in trials and points out why this is not only a missed chance to gain knowledge but also hampers the care of a group that in many cancer entities presents the majority of patients. Finally, an overview of current clinical trials and registries in Germany is presented.

Cost-utility analysis of survival with epoetin-alfa versus placebo in stage IV breast cancer.

BACKGROUND: In a multinational trial of anaemic patients with cancer receiving nonplatinum-containing chemotherapy, epoetin-alfa effectively increased haemoglobin levels, reduced red blood cell transfusion requirements, and improved QOL. Although the study was not designed or powered to evaluate survival, a survival trend was noted favouring epoetin-alfa compared with placebo (median survival 17 vs 11 months [p = 0.126]). OBJECTIVES: To determine the incremental cost utility of epoetin-alfa versus placebo in anaemic patients with stage IV breast cancer from a UK National Health Service perspective. METHODS: Patient data regarding transfusions, epoetin-alfa usage, chemotherapy treatment cycles, and adverse events were recorded, with survival follow-up for 12-36 months post-study. Stage IV breast cancer therapy costs were collected by surveying UK oncologists, and utilities for associated health states were from published sources. Costs were in British pounds and year 2000 values. Costs and benefits were jointly determined for the stage IV breast cancer subgroup (n = 55). Incremental cost-utility ratios (ICURs) were calculated assuming a 6% annual discount rate for costs and a 1.5% annual discount rate for benefits. Bootstrap simulations (10,000 iterations) were conducted to account for uncertainty, and sensitivity analyses were conducted to establish robustness. RESULTS: The ICUR for epoetin-alfa treatment was pounds 8,851 per QALY, with a 99% probability of a positive net benefit in QALYs (net benefit = 0.4805 years of perfect life) and a 94% probability of being acceptable using a threshold ICUR of pounds 30,000/QALY. The main cost drivers distinguishing epoetin-alfa from placebo were the costs of drug and patient care due to increased survival. CONCLUSIONS: The available data suggest a high probability of favourable cost-utility outcomes with epoetin-alfa treatment for anaemia in patients with stage IV breast cancer receiving nonplatinum-containing chemotherapy. Additional studies are warranted.

Prospective comparison of [18F]fluorodeoxyglucose positron emission tomography with conventional assessment by computed tomography scans and serum tumor markers for the evaluation of residual masses in patients with nonseminomatous germ cell carcinoma.

BACKGROUND: To assess the ability of [(18)F]fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET) to predict the viability of residual masses after chemotherapy in patients with metastatic nonseminomatous germ cell tumors (GCT), PET results were compared in a blinded analysis with computed tomography (CT) scans and serum tumor marker changes (TUM) as established methods of assessment. METHODS: Independent reviewers who were blinded to each other's results evaluated the PET results and corresponding CT scan and TUM results in 85 residual lesions from 45 patients. All patients were treated within prospective clinical trials and received primary/salvage, high-dose chemotherapy with autologous blood stem cell support for primary poor prognosis disease or recurrent disease. PET results were assessed both visually and by quantifying glucose uptake (standardized uptake values). Results were validated either by histologic examination of a resected mass and/or biopsy (n = 28 lesions) or by a 6-month clinical follow-up after evaluation (n = 57 lesions). RESULTS: F-18 FDG PET showed increased tracer uptake in 32 of 85 residual lesions, with 29 true positive (TP) lesions and three false positive (FP) lesions. Fifty-three lesions were classified by PET as negative (no viable GCT), 33 lesions were classified by PET as true negative (TN), and 20 lesions were classified by PET as false negative (FN). In the blinded reading of the corresponding CT scan and TUM results, 38 residual lesions were assessed correctly as containing viable carcinoma and/or teratoma. Forty-six lesions were classified as non-suspicious by CT scan/TUM (33 TN lesions and 14 falsely classified lesions). PET correctly predicted the presence of viable carcinoma in 5 of these 14 and the absence of viable carcinoma in 3 of these 14 lesions. Resulting sensitivities and specificities for the prediction of residual mass viability were as follows: PET, 59% sensitivity and 92% specificity; radiologic monitoring, 55% sensitivity and 86% specificity; and TUM, 42% sensitivity and 100% specificity. The positive and negative predictive values for PET were 91% and 62%, respectively. The diagnostic efficacy of PET did not improve when patients with teratomatous elements in the primary tumor were excluded from the analysis. In patients with multiple residual masses, a uniformly increased residual F-18 FDG uptake in all lesions was a strong predictor for the presence of viable carcinoma. CONCLUSIONS: F-18 FDG PET imaging performed in conjunction with conventional staging methods offers additional information for the prediction of residual mass histology in patients with nonseminomatous GCT. A positive PET is highly predictive for the presence of viable carcinoma. Other useful indications for a PET examination include patients with multiple residual masses and patients with marker negative disease.