Real-world anticancer medications for reproductive-age women with breast cancer by using a claims database in Japan.

Aim: To describe real-world breast cancer medications among reproductive-age women. Patients & methods: Using data from a Japanese claims database, anticancer prescriptions were classified into seven categories of amenorrhea risk based on fertility preservation guidelines. Results: We identified 2999 women with records of breast cancer and anticancer prescription from 2005 to 2018. The proportions of prescriptions were as follows: high, 4.1-12.9%; intermediate: 6.0-16.3%; low: 0.4-2.3%; very low/no: 0.3-12.2%; unknown: 33.9-45.5%; unlisted combination: 12.2-23.4%; and unlisted drug: 12.5-26.7%. The common drugs in the unknown category were trastuzumab (n = 1527), docetaxel (n = 1014), and paclitaxel (n = 995). For medications unlisted in the guidelines, various drugs and drug combinations were observed. Conclusion: Numerous anticancer drugs are currently being prescribed with insufficient evidence regarding amenorrhea risk.

Lay abstract The ability to have children for breast cancer patients is one of the key issues of cancer survivorship, especially because recent progress in anticancer treatments has enabled patients to achieve longer survival. The fertility preservation guidelines of the American Society of Clinical Oncology (2006) introduce some anticancer treatments that carry potential risks to future fertility. In this study, the anticancer prescriptions of 2999 patients with breast cancer aged between 15 and 49 years were examined. Results showed that several medications are prescribed despite the lack of information on the risk of infertility. This suggests that further research is required to fill the evidence gap, and that decision aid through adequate counseling should be undertaken.

Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): study protocol for a trial within a cohort study.

BACKGROUND: Accurate detection of patients with minimal residual disease (MRD) after surgery for stage II colon cancer (CC) remains an urgent unmet clinical need to improve selection of patients who might benefit form adjuvant chemotherapy (ACT). Presence of circulating tumor DNA (ctDNA) is indicative for MRD and has high predictive value for recurrent disease. The MEDOCC-CrEATE trial investigates how many stage II CC patients with detectable ctDNA after surgery will accept ACT and whether ACT reduces the risk of recurrence in these patients. METHODS/DESIGN: MEDOCC-CrEATE follows the 'trial within cohorts' (TwiCs) design. Patients with colorectal cancer (CRC) are included in the Prospective Dutch ColoRectal Cancer cohort (PLCRC) and give informed consent for collection of clinical data, tissue and blood samples, and consent for future randomization. MEDOCC-CrEATE is a subcohort within PLCRC consisting of 1320 stage II CC patients without indication for ACT according to current guidelines, who are randomized 1:1 into an experimental and a control arm. In the experimental arm, post-surgery blood samples and tissue are analyzed for tissue-informed detection of plasma ctDNA, using the PGDx elio™ platform. Patients with detectable ctDNA will be offered ACT consisting of 8 cycles of capecitabine plus oxaliplatin while patients without detectable ctDNA and patients in the control group will standard follow-up according to guideline. The primary endpoint is the proportion of patients receiving ACT when ctDNA is detectable after resection. The main secondary outcome is 2-year recurrence rate (RR), but also includes 5-year RR, disease free survival, overall survival, time to recurrence, quality of life and cost-effectiveness. Data will be analyzed by intention to treat. DISCUSSION: The MEDOCC-CrEATE trial will provide insight into the willingness of stage II CC patients to be treated with ACT guided by ctDNA biomarker testing and whether ACT will prevent recurrences in a high-risk population. Use of the TwiCs design provides the opportunity to randomize patients before ctDNA measurement, avoiding ethical dilemmas of ctDNA status disclosure in the control group. TRIAL REGISTRATION: Netherlands Trial Register: NL6281/NTR6455 . Registered 18 May 2017, https://www.trialregister.nl/trial/6281.

CDK4/6 inhibition in low burden and extensive metastatic breast cancer: summary of an ESMO Open-Cancer Horizons pro and con discussion.

In December 2017, ESMO Open-Cancer Horizons convened a round-table discussion on the background and latest data regarding cyclin-dependent kinase (CDK)4/6 inhibitors with endocrine therapy (ET) in the treatment of endocrine-sensitive breast cancer (BC). A review on this discussion was published in summer 2018 (https://esmoopen.bmj.com/content/3/5/e000368).Endocrine-sensitive BC with non-visceral disease and limited spread of the metastases.Endocrine-sensitive BC with non-life-threatening visceral involvement. Several open questions were identified, which led to a second ESMO Open discussion on CDK4/6 inhibitors, taking place in December 2018 and covered in this article. The panel discussed two important clinical scenarios and the pro and cons of a treatment approach with CDK4/6 inhibitors for each scenario:Endocrine-sensitive BC with non-visceral disease and limited spread of the metastases.Endocrine-sensitive BC with non-life-threatening visceral involvement. Regarding scenario 1, the panel agreed that CDK4/6 inhibitors should be recommended in first-line therapy for most patients if cost and practicality allow. However, the use of single-agent ET with an aromatase inhibitor in the first-line treatment of these patients is still a possibility for a small group of patients with very limited disease, such as one or two bone lesions or limited lymph node involvement. Regarding scenario 2, chemotherapy is the first approach for patients with endocrine-sensitive metastatic BC with life-threatening visceral involvement because of the need for a faster response. The therapeutic approaches for patients with non-life-threatening visceral involvement are still under debate. Nevertheless, CDK4/6 inhibitors are currently the treatment of choice for most patients with a close follow-up of tumour response. A treatment algorithm has been suggested at the round table.

Trends and appropriateness of perioperative chemotherapy for muscle-invasive bladder cancer.

INTRODUCTION: Contemporary guidelines recommend cystectomy with neoadjuvant or adjuvant cisplatin-based chemotherapy given with curative intent for patients with resectable muscle-invasive bladder cancer (MIBC). However, rates and appropriateness of perioperative chemotherapy utilization remain unclear. We therefore sought to characterize use of perioperative chemotherapy in older radical cystectomy MIBC patients and examine factors associated with use. METHODS: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified patients with MIBC diagnosed between 2004 and 2013 and treated with radical cystectomy. We classified patients into 3 treatment groups: cystectomy alone, neoadjuvant, or adjuvant chemotherapy. Chemotherapy was classified by regimen. We then fit a multinomial multivariable logistic regression model to assess association between patient factors with the receipt of each treatment. RESULTS: We identified 3,826 eligible patients. The majority (484; 65%) received cystectomy alone. Neoadjuvant (676; 18% overall, 69% cisplatin-based), and adjuvant chemotherapy (666, 17% overall, 55% cisplatin-based) were used in similar proportions of cystectomy patients. Over the study period, the odds of receiving adjuvant chemotherapy decreased by 7.5%, whereas neoadjuvant therapy increased by 27.5% (both P < 0.001). There was an increase in use of cisplatin-based regimens in the neoadjuvant setting (35 to 72%, P < 0.001), but not the adjuvant setting. Female gender, lower comorbidity, married status, and lower stage disease were associated with greater odds of receiving neoadjuvant chemotherapy (all P < 0.05). CONCLUSION: From 2004 to 2013 use of neoadjuvant chemotherapy for MIBC increased while use of adjuvant chemotherapy decreased. Future studies examining barriers to appropriate chemotherapy use, and the comparative effectiveness of neoadjuvant versus adjuvant chemotherapy are warranted.

Impact of Nonconcordance With NCCN Guidelines on Resource Utilization, Cost, and Mortality in De Novo Metastatic Breast Cancer.

Background: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) have directed the care of patients with cancer for >20 years. Payers are implementing guideline-based pathway programs that restrict reimbursement for non-guideline-based care to control costs, yet evidence regarding impact of guidelines on outcomes, including mortality, Medicare costs, and healthcare utilization, is limited. Patients and Methods: This analysis evaluated concordance of first treatment with NCCN Guidelines for women with de novo stage IV metastatic breast cancer (MBC) included within the SEER-Medicare linked database and diagnosed between 2007 and 2013. Cox proportional hazards models were used to evaluate the association between mortality and guideline concordance. Linear mixed-effects and generalized linear models were used to evaluate total cost to Medicare and rates of healthcare utilization by concordance status. Results: We found that 19% of patients (188/988) with de novo MBC received nonconcordant treatment. Patients receiving nonconcordant treatment were more likely to be younger and have hormone receptor-negative and HER2-positive MBC. The most common category of nonconcordant treatment was use of adjuvant regimens in the metastatic setting (40%). Adjusted mortality risk was similar for patients receiving concordant and nonconcordant treatments (hazard ratio [HR], 0.85; 95% confidence limit [CL], 0.69, 1.05). When considering category of nonconcordance, patients receiving adjuvant regimens in the metastatic setting had a decreased risk of mortality (HR, 0.60; 95% CL, 0.43, 0.84). Nonconcordant treatments were associated with $1,867 higher average Medicare costs per month compared with concordant treatments (95% CL, $918, $2,817). Single-agent HER2-targeted therapy was the highest costing category of nonconcordance at $3,008 (95% CL, $1,014, $5,001). Healthcare utilization rates were similar for patients receiving concordant and nonconcordant treatments. Conclusions: Despite a lack of survival benefit, concordant care was associated with lower costs, suggesting potential benefit to increasing standardization of care. These findings may influence policy decisions regarding implementation of pathway programs as health systems transition to value-based models.

Assessment of the quality of surgery within randomised controlled trials for the treatment of gastro-oesophageal cancer: a systematic review.

Multicentre, randomised, controlled trials (RCTs) provide level 1 evidence for surgery in the treatment of gastro-oesophageal cancer. This systematic review investigated whether standardisation of surgical techniques in RCTs reduces the variation in lymph-node harvest, in-hospital mortality, and locoregional cancer recurrence. The range in the coefficients of variation for lymph-node harvest (0.07-0.61), proportion of patients with locoregional cancer recurrence (1.1-46.2%), and in-hospital mortality (0-10%) was wide. Credentialing of surgeons through assessment of operative reports and monitoring of their performance through data collection were important factors that reduced the variation in lymph-node harvest. Factors that reduced adjusted in-hospital mortality included credentialing surgeons through procedural volume and operative reports, and standardisation of surgical techniques. Future RCTs should include an assessment of surgical performance as an important aspect of study design to reduce variation in clinical outcomes.

Management of gastric cancer in Asia: resource-stratified guidelines.

Gastric cancer is the fourth most common cancer globally, and is the second most common cause of death from cancer worldwide. About three-quarters of newly diagnosed cases in 2008 were from Asian countries. With a high mortality-to-incidence ratio, management of gastric cancer is challenging. We discuss evidence for optimum management of gastric cancer in aspects of screening and early detection, diagnosis, and staging; endoscopic and surgical intervention; and the concepts of perioperative, postoperative, and palliative chemotherapy and use of molecularly targeted therapy. Recommendations are formulated on the basis of the framework provided by the Breast Health Global Initiative, using the categories of basic, limited, enhanced, and maximum level. We aim to provide a stepwise strategy for management of gastric cancer applicable to different levels of health-care resources in Asian countries.

Time to adjuvant chemotherapy for breast cancer in National Comprehensive Cancer Network institutions.

BACKGROUND: High-quality care must be not only appropriate but also timely. We assessed time to initiation of adjuvant chemotherapy for breast cancer as well as factors associated with delay to help identify targets for future efforts to reduce unnecessary delays. METHODS: Using data from the National Comprehensive Cancer Network (NCCN) Outcomes Database, we assessed the time from pathological diagnosis to initiation of chemotherapy (TTC) among 6622 women with stage I to stage III breast cancer diagnosed from 2003 through 2009 and treated with adjuvant chemotherapy in nine NCCN centers. Multivariable models were constructed to examine factors associated with TTC. All statistical tests were two-sided. RESULTS: Mean TTC was 12.0 weeks overall and increased over the study period. A number of factors were associated with a longer TTC. The largest effects were associated with therapeutic factors, including immediate postmastectomy reconstruction (2.7 weeks; P < .001), re-excision (2.1 weeks; P < .001), and use of the 21-gene reverse-transcription polymerase chain reaction assay (2.2 weeks; P < .001). In comparison with white women, a longer TTC was observed among black (1.5 weeks; P < .001) and Hispanic (0.8 weeks; P < .001) women. For black women, the observed disparity was greater among women who transferred their care to the NCCN center after diagnosis (P (interaction) = .008) and among women with Medicare vs commercial insurance (P (interaction) < .001). CONCLUSIONS: Most observed variation in TTC was related to use of appropriate therapeutic interventions. This suggests the importance of targeted efforts to minimize potentially preventable causes of delay, including inefficient transfers in care or prolonged appointment wait times.

An evaluation of the feasibility, cost and value of information of a multicentre randomised controlled trial of intravenous immunoglobulin for sepsis (severe sepsis and septic shock): incorporating a systematic review, meta-analysis and value of information analysis.

BACKGROUND: Sepsis is a syndrome characterised by a systemic inflammatory response to infection that leads to rapid acute organ failure and potentially rapid decline to death. Intravenous immunoglobulin (IVIG), a blood product derived from human donor blood, has been proposed as an adjuvant therapy for sepsis. OBJECTIVES: To describe current practice in the management of adult patients severely ill with sepsis (severe sepsis or septic shock) in the UK; to assess the clinical effectiveness of IVIG for severe sepsis and septic shock and to obtain the appropriate inputs for the relative efficacy parameters, and the key uncertainties associated with these parameters, required to populate the decision model; to develop a decision-analytic model structure and identify key parameter inputs consistent with the decision problem and relevant to an NHS setting; and to populate the decision model and determine the cost-effectiveness of IVIG and to estimate the value of additional primary research. DATA SOURCES: Existing literature on IVIG and severe sepsis. Existing case-mix and outcome data on critical care admissions. Survey data on management of admissions with severe sepsis. Databases searched for clinical effectiveness were Cochrane Infectious Diseases Group Specialized Trials Register, the Cochrane Trials Register, MEDLINE and EMBASE. Dates searched were 1 January 2002 to 2 October 2009 to update previous Cochrane review. Databases searched for cost-effectiveness were NHS Economic Evaluation Database (NHS EED) to 2 October 2009, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations and EMBASE to 20 October 2009. REVIEW METHODS: Systematic literature searching with data extraction, descriptive analysis and clinical effectiveness and cost-effectiveness modelling of IVIG in severe sepsis. Additional primary data analysis. Expected value of information (EVI) analysis. RESULTS: Our meta-analysis, the first to simultaneously allow for type of IVIG (IVIG or immunoglobulin M-enriched polyclonal IVIG), choice of control (no treatment or albumin), study quality/publication bias and other potential covariates, indicated that the treatment effect of IVIG on mortality for patients with severe sepsis is borderline significant with a large degree of heterogeneity in treatment effect between individual studies. Modelling indicated that there were issues with bias associated with trial methodology, publication and small-study effects with the current evidence. The large degree of heterogeneity in treatment effects between studies, however, could be explained (best-fitting model) by a measure of study quality (i.e. use of albumin as control - as an indicator of proper blinding to treatment as a proxy for study quality - associated with decreased effect) and duration of IVIG therapy (longer duration associated with increased effect). In-depth discussion within the Expert Group on duration of IVIG therapy, with daily dose and total dose also clearly inter-related, indicated no clear clinical rationale for this association and exposed a lack of evidence on the understanding of the mechanism of action of IVIG in severe sepsis. Although the EVI analyses suggested substantial expected net benefit from a large, multicentre randomised controlled trial (RCT) evaluating the clinical effectiveness of IVIG, the remaining uncertainties around the design of such a study mean that we are unable to recommend it at this time. LIMITATIONS: As has been identified in previous meta-analyses, there are issues with the methodological quality of the available evidence. CONCLUSIONS: Although the results highlight the value for money obtained in conducting further primary research in this area, the biggest limitation for such research regards the uncertainties over the mechanism of action of IVIG and the heterogeneous nature of severe sepsis. Resolving these would allow for better definition of the plausibility of the effectiveness scenarios presented and, consequently, a better understanding of the cost-effectiveness of this treatment. This information would also inform the design of future, primary evaluative research. Our recommendations for future research focus on filling the knowledge gaps to inform a future multicentre RCT prior to recommending its immediate design and conduct. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Influence of race, insurance, socioeconomic status, and hospital type on receipt of guideline-concordant adjuvant systemic therapy for locoregional breast cancers.

PURPOSE: For breast cancer, guidelines direct the delivery of adjuvant systemic therapy on the basis of lymph node status, histology, tumor size, grade, and hormonal receptor status. We explored how race/ethnicity, insurance, census tract-level poverty and education, and hospital Commission on Cancer (CoC) status were associated with the receipt of guideline-concordant adjuvant systemic therapy. METHODS: Locoregional breast cancers diagnosed in 2004 (n = 6,734) were from the National Program of Cancer Registries-funded seven-state Patterns of Care study of the Centers for Disease Control and Prevention. Predictors of guideline-concordant (receiving/not receiving) adjuvant systemic therapy, according to National Comprehensive Cancer Network Guidelines, were explored by logistic regression. RESULTS: Overall, 35% of women received nonguideline chemotherapy, 12% received nonguideline regimens, and 20% received nonguideline hormonal therapy. Significant predictors of nonguideline chemotherapy included Medicaid insurance (odds ratio [OR], 0.66; 95% CI, 0.50 to 0.86), high-poverty areas (OR, 0.77; 95% CI, 0.62 to 0.96), and treatment at non-CoC hospitals (OR, 0.69; 95% CI, 0.56 to 0.85), with adjustment for age, registry, and clinical variables. Predictors of nonguideline regimens among chemotherapy recipients included lack of insurance (OR, 0.47; 95% CI, 0.25 to 0.92), high-poverty areas (OR, 0.71; 95% CI, 0.51 to 0.97), and low-education areas (OR, 0.65; 95% CI, 0.48 to 0.89) after adjustment. Living in high-poverty areas (OR, 0.78; 95% CI, 0.64 to 0.96) and treatment at non-CoC hospitals (OR, 0.68; 95% CI, 0.55 to 0.83) predicted nonguideline hormonal therapy after adjustment. ORs for poverty, education, and insurance were attenuated in the full models. CONCLUSION: Sociodemographic and hospital factors are associated with guideline-concordant use of systemic therapy for breast cancer. The identification of modifiable factors that lead to nonguideline treatment may reduce disparities in breast cancer survival.

Exclusão do procedimento 0304050164: quimioterapia adjuvante do carcinoma epidermoide de cabeça e pescoço da tabela do SUS / Exclusion of procedure 0304050164: adjuvant chemotherapy of epidermoid carcinoma of the head and neck of the SUS table

A DOENÇA: O carcinoma epidermoide, também denominado escamocelular ou espinocelular, é o tipo histológico mais comum de câncer de cabeça e pescoço e inclui variantes queratinizantes (carcinomas bem diferenciados) e não queratinizantes, estas por vezes distinguíveis apenas por exame imuno-histoquímico de outras neoplasias malignas que podem acometer de modo primário ou secundário as estruturas da região: adenocarcinoma, melanoma, linfoma e sarcoma. Os tumores que acometem com maior frequência a cavidade nasal e seios paranasais são o estesioneuroblastoma (47%), adenocarcinoma (24%) e carcinoma indiferenciado (22%) e apresentam um prognóstico ruim mesmo com os melhores tratamentos disponíveis (ressecção cirúrgica por via endoscópica ou cranofacial, seguida por irradiação isolada ou radioquimioterapia pós-operatória). TRATAMENTO: As principais modalidades terapêuticas para o CECP são a cirurgia e a radioterapia, visando à erradicação da doença no sítio primário e na rede de drenagem linfática próxima ao tumor. A cirurgia tem a vantagem de permitir o estadiamento patológico do pescoço, evitando o tratamento com radiação quando desnecessário e indicando os casos em que a terapia adjuvante deve ser empregada. A radioterapia confere chance de controle locorregional do CECP. O principal desafio para esse tratamento é a necessidade de aplicação de doses de radiação relativamente altas em tumores (ou áreas de risco) de localizações muito próximas a estruturas críticas, como a base do crânio, medula espinhal, tronco cerebral e aparato óptico. O planejamento ou a técnica de radioterapia utilizados podem impactar na qualidade de vida, dado o potencial de lesão de estruturas responsáveis pela produção de saliva, paladar, função oral, audição, fala e deglutição. A cirugia é a modalidade de tratamento principal para doentes com câncer de hipofaringe (laringectomia total com faringectomia parcial ou faringolaringectomia) e laringe (laringectomia quase total ou laringectomia total), mas cirurgias com preservação do órgão da fonação podem ser oferecidas ao doente, desde que ele conte com acompanhamento multiprofissional. A quimioterapia prévia não é recomendada como tratamento inicial padrão para a maioria dos doentes com CECP avançado, pois sua morbidade é elevada e não está associada a benefício clínico inequívoco em termos de melhora estatisticamente significativa na sobrevida global, recidiva locorregional ou na sobrevida livre de doença. A quimioterapia adjuvante não é recomendada após tratamento locorregional definitivo com cirurgia ou radioquimioterapia, pois a despeito de sua morbidade não reduz a chance de recidiva a distância ou morte pela doença. Relativamente ao carcinoma de nasofaringe, a radioterapia é a principal modalidade terapêutica para o carcinoma da nasofaringe, que historicamente resulta no controle da doença para 50%-70% dos casos. DELIBERAÇÃO FINAL: os membros da CONITEC presentes na 34ª reunião do plenário, realizada nos dias 1/4 e 2/4/2015, recomendaram a exclusão do procedimento 0304050164 - quimioterapia adjuvante do carcinoma epidermoide de cabeça e pescoço da Tabela de Procedimentos, Medicamentos, Órteses/Próteses e Materiais Especiais do SUS. DECISÃO: PORTARIA Nº 20, de 27 de maio de 2015 - Torna pública a decisão de excluir a quimioterapia adjuvante do carcinoma epidermoide de cabeça e pescoço da Tabela do SUS.

[Impact of the new guidelines for adjuvant systemic treatment of breast cancer at hospital level]. / Gevolgen op ziekenhuisniveau van de nieuwe richtlijnen voor adjuvante systemische behandeling bij mammacarcinoom.

Recently, the Dutch Society for Medical Oncology published new consensus guidelines for the use of adjuvant systemic treatment in patients with operable breast cancer. We used data of the cancer registry of the Comprehensive Cancer Centre South to predict the change in the number of patients who will be candidates for systemic treatment according to these new guidelines. It was estimated that of all patients with operable breast cancer, 15% should receive chemotherapy, 27% hormonal therapy and 17% a combination of both modalities. Of the patients with negative axillary lymph nodes, one-third will receive adjuvant systemic treatment. Compared with the previous guidelines, the introduction of the new guidelines will cause a 50% increase in the number of patients receiving adjuvant systemic treatment in Dutch hospitals.

How courts view experimental treatments.

The consequences of lawsuits brought by patients to obtain insurance coverage for autologous bone marrow treatment for breast cancer illustrate the problems that arise when health plans seek to exclude "experimental" treatments.