Beyond hazard ratios: appropriate statistical methods for quantifying the clinical effectiveness of immune-oncology therapies - the example of the Netherlands.

BACKGROUND: The Dutch Committee for the Evaluation of Oncological Drugs evaluates the effectiveness of new oncological treatments. The committee compares survival endpoints to the so-called PASKWIL-2023 criteria for palliative treatments, which define if treatment effects are considered clinically relevant. A positive recommendation depends on whether the median overall survival (OS) is below or above 12 months in the comparator arm. If the former applies, an OS benefit of at least 12 weeks, and a hazard ratio (HR) smaller than 0.7 are required. If the latter applies, an OS or progression free survival (PFS) benefit of at least 16 weeks, and an HR smaller than 0.7 are required. Nonetheless, the median survival time may not be reached and the proportional hazards (PH) assumption, quantified by the HR, is likely violated for immuno-oncology (IO) therapies, deeming these criteria inappropriate. METHODS: We conducted a systematic literature review to identify statistical methods used to represent the clinical effectiveness of IO therapies based on trial data. We searched MEDLINE and EMBASE databases from inception to August 31, 2022, limited to English papers. Methodological studies, randomized controlled trials, and discussion papers recognising key issues of survival data analysis of IO therapies were eligible for inclusion. RESULTS: A total of 1,035 unique references were identified. After full paper screening, 17 publications were included in the review. Additionally, 43 papers were identified through 'snowballing'. We conclude that the current PASKWIL-2023 criteria are methodologically incorrect under non-PH. In that case, single summary statistics fail to capture the treatment effect and any measure should be interpreted in combination with the Kaplan-Meier curves. We recommend 'parameter-free' measures, such as the difference in restricted mean survival time, avoiding assumptions on the underlying survival. CONCLUSIONS: The HR is commonly used to assess treatment effectiveness, without investigating the validity of the PH assumption. This happens with the application of the PASKWIL-2023 criteria for palliative oncology treatments, which can only be valid under a PH setting. Under non-PH, alternative treatment effect measures are suggested. We propose a step-by-step approach supporting the choice of the most appropriate methods to quantify treatment effectiveness that can be used to redefine the PASKWIL-2023 criteria, or similar criteria in other clinical areas.

International Society of Paediatric Oncology (SIOP) Global Mapping Program: Analysis of healthcare centers in countries of the Latin American Society of Pediatric Oncology (SLAOP).

BACKGROUND: The International Society of Paediatric Oncology Society Global Mapping Program aims to describe the local pediatric oncology capacities. Here, we report the data from Latin America. METHODS: A 10-question survey was distributed among chairs of pediatric oncology services. Centers were classified according to patient volume into high- (HVC; 100 or more new cases per year), medium- (MVC; 31-99 cases), and low-volume centers (LVC; 30 cases or less), respectively. National referral centers (NRC) were identified. RESULTS: Total 307 centers in 20 countries were identified (271 responded), and 264 responses were evaluable, accounting for 78% of the expected cases (21,359 cases per year). Seventy-seven percent of patients are treated in public centers, including additional support by civil society organizations. We found that 66% of the patients are treated in 70 centers of excellence, including 21 NRC. There was a median of one pediatric oncologist every 21 newly diagnosed patients (44 for NRC), and in 84% of the centers, nurses rotated to other services. A palliative care team was lacking in 25% of the centers. LVC with public funding have significantly lower probability of having a palliative care team or trained pediatric oncology surgeons. Psychosocial, pharmacy, and nutrition services were available in more than 93% of the centers. No radiotherapy facility was available on campus in nine of 21 NRC. CONCLUSIONS: Most children with cancer in Latin America are treated in public HVC. There is a scarcity of pediatric oncologists, specialized nurses and surgeons, and palliative care teams, especially in centers with public funding.

Secondary Endpoint Utilization and Publication Rate among Phase III Oncology Trials.

Secondary endpoints (SEP) provide crucial information in the interpretation of clinical trials, but their features are not yet well understood. Thus, we sought to empirically characterize the scope and publication rate of SEPs among late-phase oncology trials. We assessed SEPs for each randomized, published phase III oncology trial across all publications and ClinicalTrials.gov, performing logistic regressions to evaluate associations between trial characteristics and SEP publication rates. After screening, a total of 280 trials enrolling 244,576 patients and containing 2,562 SEPs met the inclusion criteria. Only 22% of trials (62/280) listed all SEPs consistently between ClinicalTrials.gov and the trial protocol. The absolute number of SEPs per trial increased over time, and trials sponsored by industry had a greater number of SEPs (median 9 vs. 5 SEPs per trial; P < 0.0001). In total, 69% of SEPs (1,770/2,562) were published. The publication rate significantly varied by SEP category [X2 (5, N = 2,562) = 245.86; P < 0.001]. SEPs that place the most burden on patients, such as patient-reported outcomes and translational correlatives, were published at 63% (246/393) and 44% (39/88), respectively. Trials with more SEPs were associated with lower overall SEP publication rates. Overall, our findings are that SEP publication rates in late-phase oncology trials are highly variable based on the type of SEP. To avoid undue burden on patients and promote transparency of findings, trialists should weigh the biological and clinical relevance of each SEP together with its feasibility at the time of trial design. SIGNIFICANCE: In this investigation, we characterized the utilization and publication rates of SEPs among late-phase oncology trials. Our results draw attention to the proliferation of SEPs in recent years. Although overall publication rates were high, underpublication was detected among endpoints that may increase patient burden (such as translational correlatives and patient-reported outcomes).

Is the Medical Oncology Workforce in Canada in Jeopardy? Findings from the Canadian Association of Medical Oncologists' COVID-19 Impact Survey Series.

The COVID-19 (C19) pandemic introduced challenges in all areas of the Canadian healthcare system. Along with adaptations to clinical care environments, there was increasing concern about physician burnout during this time. The Canadian Association of Medical Oncologists (CAMO) has examined the effects of the pandemic on the medical oncology (MO) workforce. A series of four multiple choice web-based surveys distributed to MOs who were identified using the Royal College of Physicians and Surgeons directory and CAMO membership in May 2020 (S1), July 2020 (S2), December 2020 (S3), and March 2022 (S4). Descriptive analyses were performed for each survey, and a Chi-square test (α = 0.05) was used to assess factors associated with planned change in practice in S4. The majority of respondents work in a comprehensive cancer center S1/S2/S3/S4 (87%/86%81%/88%) and have been in practice >10 years (56%/61%/50%/64%). The most commonly reported personal challenges were physical (60%) and mental (60%) wellness. In S4, 47% of MOs reported dissatisfaction with their current work-life balance. In total, 83% reported that their workload has increased since the beginning of C19, and 51% of MOs reported their future career plans have been impacted by C19. In total, 56% of respondents are considering retiring or reducing total working hours in the next 5 years. Since the onset of the C19 pandemic, there are concerns identified with wellness, increasing workload, and job dissatisfaction among MOs, associated with experienced staff who have >10 years in practice. As rates of cancer prevalence rise and treatments become more complex, it is crucial to address the concerns raised in these surveys to ensure that we have a stable MO workforce in the future.

Impact of Location of Residence and Distance to Cancer Centre on Medical Oncology Consultation and Neoadjuvant Chemotherapy for Triple-Negative and HER2-Positive Breast Cancer.

Despite consensus guidelines, most patients with early-stage triple-negative (TN) and HER2-positive (HER2+) breast cancer do not see a medical oncologist prior to surgery and do not receive neoadjuvant chemotherapy (NAC). To understand barriers to care, we aimed to characterize the relationship between geography (region of residence and cancer centre proximity) and receipt of a pre-treatment medical oncology consultation and NAC for patients with TN and HER2+ breast cancer. Using linked administrative datasets in Ontario, Canada, we performed a retrospective population-based analysis of women diagnosed with stage I-III TN or HER2+ breast cancer from 2012 to 2020. The outcomes were a pre-treatment medical oncology consultation and the initiation of NAC. We created choropleth maps to assess the distribution of the outcomes and cancer centres across census divisions. To assess the relationship between distance to the nearest cancer centre and outcomes, we performed multivariable regression analyses adjusted for relevant factors, including tumour extent and nodal status. Of 14,647 patients, 29.9% received a pre-treatment medical oncology consultation and 77.7% received NAC. Mapping demonstrated high interregional variability, ranging across census divisions from 12.5% to 64.3% for medical oncology consultation and from 8.8% to 64.3% for NAC. In the full cohort, compared to a distance of ≤5 km from the nearest cancer centre, only 10-25 km was significantly associated with lower odds of NAC (OR 0.83, 95% CI 0.70-0.99). Greater distances were not associated with pre-treatment medical oncology consultation. The interregional variability in medical oncology consultation and NAC for patients with TN and HER2+ breast cancer suggests that regional and/or provider practice patterns underlie discrepancies in the referral for and receipt of NAC. These findings can inform interventions to improve equitable access to NAC for eligible patients.

The effects of Asian American Pacific Islander (AAPI) data inequities in gynecologic oncology.

Asian American and Pacific Islanders (AAPI) are the fastest growing racial group in the United States. Data on AAPI communities, however, are significantly limited. The oversimplification and underreporting of this ethnically and socioeconomically heterogenous population through the use of aggregated data has deleterious effects and worsens disparities in patient treatment, outcomes, and experiences. Gynecologic oncology disparities do not exist in a vacuum, and are rooted in larger cultural gaps in our understanding and delivery of healthcare. In this paper, we aim to demonstrate how AAPI data inequities have negative downstream effects on research and public health policies and initiatives, and also provide a call to action with specific recommendations on how to improve AAPI data equity within these realms.

An Evaluation of Novel Oncology Approvals with a PMR/C for Assessing Data in Racial and Ethnic Populations Underrepresented in Premarket Clinical Trials.

Clinical trials supporting oncology drug approvals frequently underrepresent diverse racial and ethnic populations. Recent policies have focused on ensuring premarket clinical trials are more inclusive and representative of racial and ethnic diversity in the general U.S. population or intended patient population; however, recent U.S. Food and Drug Administration (FDA) guidance on postmarketing approaches to collecting data in underrepresented populations demonstrates that, in certain circumstances, postmarketing requirements and/or commitments (PMR/Cs) may be issued to conduct more representative studies if there are remaining questions about safety or efficacy. This analysis demonstrates that prior to 2020, no drugs had PMR/Cs to further characterize use in a more representative population, and in the last 3 years, more than half of novel oncology approvals have had such a PMR/C (21/40, 53%). In addition, this analysis helps to identify characteristics, such as single-arm pivotal trial design, U.S. enrollment, and results of safety subgroup analyses based on race and ethnicity, that may contribute to decisions to issue a PMR/C to conduct a study that is more representative of the racial and ethnic diversity of the U.S. or intended patient population. These results can inform efforts to improve premarket clinical trials to ensure they are representative and able to characterize use in any patient who may need the drug.

Improving quality of care by standardising patient data collection in electronic medical records in an oncology department in Spain.

BACKGROUND: Evaluation of quality of care in oncology is key in ensuring patients receive adequate treatment. American Society of Clinical Oncology's (ASCO) Quality Oncology Practice Initiative (QOPI) Certification Program (QCP) is an international initiative that evaluates quality of care in outpatient oncology practices. METHODS: We retrospectively reviewed free-text electronic medical records from patients with breast cancer (BR), colorectal cancer (CRC) or non-small cell lung cancer (NSCLC). In a baseline measurement, high scores were obtained for the nine disease-specific measures of QCP Track (2021 version had 26 measures); thus, they were not further analysed. We evaluated two sets of measures: the remaining 17 QCP Track measures, as well as these plus other 17 measures selected by us (combined measures). Review of data from 58 patients (26 BR; 18 CRC; 14 NSCLC) seen in June 2021 revealed low overall quality scores (OQS)-below ASCO's 75% threshold-for QCP Track measures (46%) and combined measures (58%). We developed a plan to improve OQS and monitored the impact of the intervention by abstracting data at subsequent time points. RESULTS: We evaluated potential causes for the low OQS and developed a plan to improve it over time by educating oncologists at our hospital on the importance of improving collection of measures and highlighting the goal of applying for QOPI certification. We conducted seven plan-do-study-act cycles and evaluated the scores at seven subsequent data abstraction time points from November 2021 to December 2022, reviewing 404 patients (199 BR; 114 CRC; 91 NSCLC). All measures were improved. Four months after the intervention, OQS surpassed the quality threshold and was maintained for 10 months until the end of the study (range, 78-87% for QCP Track measures; 78-86% for combined measures). CONCLUSIONS: We developed an easy-to-implement intervention that achieved a fast improvement in OQS, enabling our Medical Oncology Department to aim for QOPI certification.

Provider perceptions of barriers to biosimilar utilization in community oncology practices.

BACKGROUND: Biosimilars reduce the burden of cost on patients and payers, and so doing, increase access to life-saving care. However, biosimilar uptake in the US has been inconsistent. OBJECTIVES: This study assessed provider perceptions of barriers to biosimilar use and their relationships to utilization rates in a large, national oncology network and examined if perceptions differed by demographic and practice characteristics. METHODS: A 28-item survey was administered to 400 network physicians, pharmacists, nurses, and administrators, spanning 25 provider groups, and measured 1) barriers to use categorized into 4 subscales-payer-related, provider-related, operational, and patient-related, using a Likert scale ranging from Never (1) to Always (5); and 2) demographic and practice characteristics. Utilization rates were assessed using aggregated patient-level drug administration data found in the electronic health record system. Descriptive and inferential statistics were used to describe responses and assess relationships between variables. RESULTS: A total of 46 responses were analyzed, with a response rate of 11.5%. Most respondents were female (55.6%), physicians (52.2%), with over 6 years of experience (67%). A majority worked in practices participating in the Oncology Care Model (86.7%) and received continuing education on biosimilars (84.8%). Overall scale score was moderately low (mean=2.31), indicating low levels of perceived barriers. The lowest subscale score was operational barriers (mean=2.21), while payer-related barriers was the highest (mean=2.78). Perceptions of barriers did not differ based on demographic and practice characteristics. The average biosimilar utilization rate was 66.2%, with practices in the West administering biosimilars most frequently (71.8%). Utilization was not impacted by perceptions of barriers. CONCLUSION: Perceived barriers to biosimilar utilization were not common and not associated with utilization. Infrequent impediments to utilization may be associated with network-wide emphasis on continuing education and a value-based care environment. Future research should consider other practice- and patient-level factors that may impact biosimilar utilization.

Real-world evidence in the reassessment of oncology therapies: payer perceptions from five countries.

Aim: This study explored the perceived value of real-world evidence (RWE) in the reassessment of oncology therapies by collecting the perspectives of health technology assessment/payer decision-makers.Materials & methods: A web-based survey was conducted using the Market Access Transformation Rapid Payer Response online portal. 30 participants from France, Germany, Spain, the UK and the USA were recruited based on their expertise.Results: Participants agreed that the most common uses of RWE are to confirm efficacy and safety results from randomized controlled trials and to reevaluate the projected utilization of an oncology therapy. We found variability in other reported uses of RWE.Conclusion: The organizations developing RWE should ensure that their plans recognize the heterogeneity in payer perceptions.

A survey from the Market Access Transformation RPR portal queried decision-makers from five countries about the value of real-world evidence in oncology therapy reassessment. Participants agreed that RWE can confirm efficacy/safety and reevaluate utilization, but other uses varied.

Ambulatory Routine Care in Oncology in Germany: Real-World Survival Data.

INTRODUCTION: Survival data reported by randomised controlled trials are collected in a highly selected patient population and can thus only be transferred to a limited extent to real-world patients: the patients in routine care are mostly older, present with more comorbidities and a worse general state of health. This so-called efficacy-effectiveness gap typically results in inferior survival data in routine healthcare. METHODS: Six prospective clinical tumour registries recruited a total of 11,679 patients receiving systemic therapy in haemato-oncological practices in Germany between 2006 and 2020. For these patients with advanced colorectal cancer, breast cancer, lung cancer, pancreatic cancer, renal cell cancer, and lymphatic neoplasms, overall survival was analysed. A comprehensive literature search was performed to identify suitable pivotal randomised controlled trials. RESULTS: Median overall survival of patients treated in German routine care, with advanced colorectal, breast, lung, and pancreatic cancer, as well as with diffuse large B-cell lymphoma and multiple myeloma, is not shorter than the respective survival data reported in trials. Patients with advanced renal cell carcinoma, chronic lymphocytic leukaemia, or indolent non-Hodgkin lymphoma showed slightly lower survival rates compared to clinical trials. CONCLUSIONS: Despite less favourable patient characteristics, survival data from patients with cancer treated in ambulatory routine care in Germany are in range with results from randomised controlled studies.

The Association Between Oncology Outreach and Timely Treatment for Rural Patients with Breast Cancer: A Claims-Based Approach.

BACKGROUND: Oncology outreach is a common strategy for increasing rural access to cancer care, where traveling oncologists commute across healthcare settings to extend specialized care. Examining the extent to which physician outreach is associated with timely treatment for rural patients is critical for informing outreach strategies. METHODS: We identified a 100% fee-for-service sample of incident breast cancer patients from 2015 to 2020 Medicare claims and apportioned them into surgery and adjuvant therapy cohorts based on treatment history. We defined an outreach visit as the provision of care by a traveling oncologist at a clinic outside of their primary hospital service area. We used hierarchical logistic regression to examine the associations between patient receipt of preoperative care at an outreach visit (preoperative outreach) and > 60-day surgical delay, and patient receipt of postoperative care at an outreach visit (postoperative outreach) and > 60-day adjuvant delay. RESULTS: We identified 30,337 rural-residing patients who received breast cancer surgery, of whom 4071 (13.4%) experienced surgical delay. Among surgical patients, 14,501 received adjuvant therapy, of whom 2943 (20.3%) experienced adjuvant delay. In adjusted analysis, we found that patient receipt of preoperative outreach was associated with reduced odds of surgical delay (odds ratio [OR] 0.75, 95% confidence interval [CI] 0.61-0.91); however, we found no association between patient receipt of postoperative outreach and adjuvant delay (OR 1.04, 95% CI 0.85-1.25). CONCLUSIONS: Our findings indicate that preoperative outreach is protective against surgical delay. The traveling oncologists who enable such outreach may play an integral role in catalyzing the coordination and timeliness of patient-centered care.

Gender and Racial Diversity Among Obstetrics and Gynecology Departments and Gynecologic Oncology Divisions in Canada: Are We There Yet?

OBJECTIVES: Gender and racial diversity in academic Canadian departments of obstetrics and gynecology (OBGYN) have not been previously described. We examined gender representation in leadership in academic OBGYN departments and gynecologic oncology (GO) divisions, and determined factors predictive of leadership and promotion including racialized status. METHODS: This cross-sectional study of Canadian residency-affiliated academic OBGYN departments queried institutional websites in January 2021 to compile a list of academic faculty. Subjective gender was assessed using photographs and pronouns, and racialized status was determined using photographs. Logistic regression analyses determined predictive factors for leadership roles. Fassiotto et al. rank equity indices (REI) and Hofler et al. representation ratios were calculated. RESULTS: Within 16 Canadian institutions there were 354 (33.6%) men and 699 (66.4%) women, with 18.3% racialized faculty. Men were more likely to reach full professorship (P < 0.00001) and leadership positions of department chair, vice-chair or division head (P = 0.01). Representation ratios for women in OBGYN were <1 for all administrative leadership positions, and pairwise comparisons of the probability of promotion for women OBGYNs using REI reveal significant disparities between senior and junior administrative leadership and professorial ranks. Racialized physicians were less likely to have attained full professorship (P = 0.002). Ninety-seven academic GOs were identified: 68 (70.1%) were women, 17 (17.5%) racialized. Seven GO divisions (44%) had no racialized members. On multivariate analysis, only year of completion of fellowship was predictive of leadership. CONCLUSION: In academic Canadian OBGYN departments women are underrepresented in leadership and full professor positions. Racialized faculty are underrepresented in full professorship.

[Feedback on the first three years of application of the reform of the third cycle in oncology]. / La phase socle en oncologie : retour d'expérience sur les trois premières années d'application de la réforme du troisième cycle.

Since the establishment of the reform of medical studies' third cycle in 2017, the first two residency semesters define the "phase socle" whose objective is to provide the basic knowledge of the specialty. We have carried out a declarative survey, submitted in 2020 to all French residents in Oncology whose "phase socle" had taken place during the first 3 years of the reform. The main objectives of this survey were to evaluate the theoretical teaching of oncology as well as the practical hospital training provided during this phase. The response rate was 44% (among 355 residents, 155 answered). In terms of theoretical training, the level of satisfaction with the national teaching courses of the Collège National des Enseignants en Cancérologie and the distant learning courses on the SIDES-NG platform was considered satisfactory (average visual analog scale of 6.7/10 and 5.7/10, respectively). There was greater heterogeneity in the organization of local courses, of which only 50% of base phase residents benefited. In terms of practical training, the training value of the medical oncology and radiation oncology residencies was good (visual analogue scale 7.9/10 and 6.7/10, respectively), with educational objectives adapted to the base phase, but with a greater workload for medical oncology. This study provides feedback that shows the success of this reform in oncology. It also offers suggestions, which could be the basis to improve the formation of oncology residents.

An Italian Model for the Management of Cancer Patients during COVID-19 Pandemic: The Regional Center for Oncological Orientation (COrO) of Taranto (ROP).

OBJECTIVE: The recent outbreak of COVID-19 limited the resources of the National Health System necessitating the formulation of novel practice recommendations for oncological care. To date, management guidelines for cancer patients in case of pandemic are not available. Each center tried to manage its own needs and requests independently, often reducing access to treatment and diagnostic exams to patients. Here, we have described the management of cancer patients during COVID-19 infection with suggestions of some practical approaches applied by our Regional Center for Oncological Orientation (COrO) in S.G. Moscati Hospital (Taranto, Italy). SUBJECTS AND METHODS: Our strategy was to minimize any interruption of cancer treatment through the extension of Taranto's Health Regional (COrO). The extension of the oncological network, assisted by the General Management of Taranto ASL through agreements with private structures in Taranto's area, allowed cancer patients to receive up to 11 different types of services, according to their needs (first investigation or follow-up), and represents an exclusive organization on the entire Italian territory. RESULTS: Thanks to the organization of the COrO in 2020, 1,406 first oncological visits and 566 preparatory treatments were carried out, 372 of exemption for oncological pathology (free health care) were activated, and 1,742 instrumental investigations and 7 cases of civil invalidity were performed (certificate of disability). CONCLUSIONS: We have overcome barriers to care of oncology patients leading to a reduction of waiting lists representing a practical application model that can be extended to other healthcare settings.

Internações oncológicas: perfil epidemiológico dos pacientes internados no ano de 2021 do Hospital do Servidor Público Municipal de São Paulo / Oncological hospitalizations: epidemiological profile of patients hospitalized in 2021 at the Hospital do Servidor Público Municipal de São Paulo

Introdução: O câncer é uma doença causada por uma multiplicação celular desordenada ocasionada por mutação nos genes que codificam as proteínas reguladoras do ciclo celular, fazendo com que as células cancerosas apresentem diferentes características. O número de casos novos de câncer cresce a cada ano. A estimativa do INCA para 2020/2022 é a incidência de 625mil casos novos de câncer no Brasil para cada um dos anos. Objetivo: analisar e descrever o perfil epidemiológico dos pacientes internados pela oncologia do serviço Hospital Servidor Público Municipal no ano de 2021. Metodologia: trata-se de um estudo observacional, retrospectivo e com abordagem descritiva. A população é formada por pacientes do sexo feminino e masculino que foram internados pela especialidade no ano de 2021 e que possuíam idade igual ou maior de 18 anos. Resultados: Foram observadas 149 internações, sendo 125 pacientes que entraram nos critérios de inclusão e foram estudados quanto às variáveis. Do total de pacientes estudados, 60% são pessoas do sexo masculino, sendo a faixa etária mais prevalente entre 50-69 anos. Quanto ao sítio primário, a maior parte da amostra tinha o diagnóstico de neoplasia de mama e o principal fator de risco citado foi o tabagismo. A presença avançada constitui 71,2% da incidência ao todo nestes doentes. Conclusão: Os resultados desse estudo apontaram para a importância de se repensar a efetividade no atendimento ao paciente oncológico, a equidade do acesso na atenção hospitalar, o investimento de recursos nos programas de cuidados paliativos e como amenizar as desigualdades regionais brasileiras na saúde. Palavras-chave: Câncer. Aspectos epidemiológicos. Pacientes oncológicos. Tratamento.