Efficacy-effectiveness gaps in oncology: Looking beyond survival.

The efficacy-effectiveness (EE) gap describes the differences in survival seen in clinical trials and routine clinical practice, where patients in real-world practice often have inferior outcomes compared to trial populations. However, EE gaps may exist beyond survival outcomes, including gaps in quality of life, toxicity, cost-effectiveness, and patient time, and these EE gaps should also influence patient and clinician treatment decisions. Failure to clearly acknowledge these EE gaps may cause patients, clinicians, and health care systems to have unrealistic expectations of the benefits of therapy across a range of important clinical and economic domains. In this commentary, the authors review the evidence supporting the existence of EE gaps in quality of life, time toxicity, cost and toxicities, and urge for further research into this important topic.

Factors associated with the melanoma diagnostic interval in Ontario, Canada: a population-based study.

BACKGROUND: Protracted times to diagnosis of cancer can lead to increased patient anxiety, and in some cases, disease progression and worse outcomes. This study assessed the time to diagnosis for melanoma, and its variability, according to patient-, disease-, and system-level factors. METHODS: This is a descriptive, cross-sectional study in Ontario, Canada from 2007-2019. We used administrative health data to measure the diagnostic interval (DI)-and its two subintervals-the primary care subinterval (PCI) and specialist care subinterval (SCI). Multivariable quantile regression was used. RESULTS: There were 33,371 melanoma patients. The median DI was 36 days (interquartile range [IQR]: 8-85 days), median PCI 22 days (IQR: 6-54 days), and median SCI 6 days (IQR: 1-42 days). Increasing comorbidity was associated with increasing DI. Residents in the most deprived neighbourhoods and those in rural areas experienced shorter DIs and PCIs, but no differences in SCI. There was substantial variation in the DI and SCI across health regions, but limited differences in the PCI. Finally, patients with a history of non-melanoma skin cancer, and those previously established with a dermatologist experienced significantly longer DI, PCI, and SCI. DISCUSSION: This study found variability in the melanoma DI, notably by system-level factors.

Incidence, Mortality, and Survival of Merkel Cell Carcinoma: A Systematic Review of Population Based-Studies.

BACKGROUND: Merkel Cell Carcinoma (MCC) is a rare, aggressive skin cancer that most commonly occurs in UV-exposed body sites. Its epidemiology in different geographies and populations is not well characterised. OBJECTIVE: The objective of this systematic review is to summarize evidence on the incidence, mortality, and survival rates of MCC from population-based studies. METHODS: We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from database inception to June 6th, 2023. No geographic, age or date exclusions were applied. We included population-based studies of MCC that reported the incidence, survival, or mortality rate, and considered systematic reviews. A data-charting form was created and validated to identify variables to extract. Two reviewers then independently charted the data for each included study with patient characteristics, and estimates of incidence rate, mortality rate, and survival rate and assessed the quality of included studies using the Joanna Briggs Institute Checklist for Prevalence studies, Newcastle-Ottawa Scale and Assessment of Multiple Systematic Reviews. We abstracted age-, sex-, stage- and race-stratified outcomes, and synthesized comparisons between strata narratively and using vote counting. We assessed the certainty of evidence for those comparisons using the Grading of Recommendations, Assessments, Developments and Evaluations framework. RESULTS: We identified 11,472 citations, of which 52 studies from 24 countries met our inclusion criteria. Stage 1 and the head and neck were the most frequently reported stage and location at diagnosis. The incidence of MCC is increasing over time (high certainty), with the highest reported incidences reported in Southern hemisphere countries (Australia [2.5 per 100,000], New Zealand [0.96 per 100,000]) (high certainty). Male patients generally had higher incidence rates compared to female patients (high certainty), although there were some variations over time periods. Survival rates varied, with lower survival and/or higher mortality associated with male sex (moderate certainty), higher stage at diagnosis (moderate-to-high certainty), older age (moderate certainty), and immunosuppression (low-to-moderate certainty). CONCLUSIONS: MCC is increasing in incidence and may increase further given the ageing population of many countries. The prognosis of MCC is poor, particularly for males, those who are immunosuppressed, and patients diagnosed at higher stages or at an older age.

Prioritising locations for radiotherapy equipment in Brazil: a cross-sectional, population-based study and development of a LINAC shortage index.

BACKGROUND: Similarly to several other upper-middle-income countries, there is a major shortfall in radiotherapy services for the treatment of cancer in Brazil. In this study, we developed the linear accelerator (LINAC) shortage index to assess the LINAC shortage and support the prioritisation of new LINAC distribution in Brazil. METHODS: This cross-sectional, population-based study used data from the National Cancer Institute 2020 Cancer estimates, the Ministry of Health 2019 radiotherapy census, the Minister of Health radiotherapy expansion programme progress reports, and the Fundação Oncocentro de São Paulo public database of the Cancer Hospital Registry of the State of São Paulo to calculate the LINAC shortage index. Data collected were number of new cancer cases in Brazil, number of LINACs per region and state, number of cancer cases treated with radiotherapy, patient state of residence, and radiotherapy treatment centre and location. National, regional, and state-level data were collected for analysis. LINAC numbers, cancer incidence, geographical distribution, and radiotherapy needs were estimated. A LINAC shortage index was calculated as a relative measure of LINAC demand compared with supply based on number of new cancer cases, number of patients requiring radiotherapy, and the number of LINCAS in the region or state. We then built a prioritisation framework using the LINAC shortage index, cancer incidence, and geographical factors. Finally, using patient-level public cancer registry data from the Fundação Oncocentro de São Paulo and Google maps, we estimated the geospatial distance travelled by patients with cancer from their state of residence to radiotherapy treatment in São Paulo from 2005-14. Non-parametric statistics were used for analysis. FINDINGS: Data were collected between Feb 2 and Dec 31, 2021. In 2020, there were 625 370 new cancer cases in Brazil and 252 LINAC machines. The number of LINACs was inadequate in all Brazilian regions, with a national LINAC shortage index of 221 (ie, 121% less than the required radiotherapy capacity). The LINAC shortage index was higher in the midwest (326), north (313), and northeast (237) regions, than the southeast (210) and south (192) regions. Four states (Tocantins, Acre, Amapá, and Roraima) in the north region were ranked first on the prioritisation rank due to no availability of LINACs. There was an association between LINAC shortage index and the number of patients who travelled to receive radiotherapy (p<0·0001). Patients living in the midwest (793 km), north (2835 km), and northeast (2415 km) regions travelled significantly longer average distances to receive radiotherapy treatment in São Paulo than patients living in the southeast or south regions (p=0·032). The reduced number of LINACs in these regions was associated with longer distance travelled (p=0·032). INTERPRETATION: There is substantial discordance between distribution of cancer cases and LINAC availability in Brazil. We developed a tool using the LINACs shortage index to help prioritise the development of radiotherapy infrastructure across Brazil; this approach might also be useful in other health systems. FUNDING: None.

A population-based validation study of the 8th edition UICC/AJCC TNM staging system for cutaneous melanoma.

BACKGROUND: The 8th edition UICC/AJCC TNM8 (Tumour, Nodes, Metastasis) melanoma staging system introduced several modifications from the 7th edition (TNM7), resulting in changes in survival and subgroup composition. We set out to address the limited validation of TNM8 (stages I-IV) in large population-based datasets. METHODS: This retrospective cohort-study included 6,414 patients from the population-based Ontario Cancer Registry diagnosed with cutaneous melanoma between January 1, 2007 and December 31, 2012. Kaplan-Meier curves estimated the melanoma-specific survival (MSS) and overall survival (OS). Cox proportional hazard models were used to estimate adjusted hazard ratios for MSS and OS across stage groups. The Schemper-Henderson measure was used to assess the variance explained in the Cox regression. RESULTS: In our sample, 21.3% of patients were reclassified with TNM8 from TNM7; reclassifications in stage II were uncommon, and 44.1% of patients in stage III were reclassified to a higher subgroup. Minimal changes in MSS curves were observed between editions, but the stage IIB curve decreased and the stage IIIC curve increased. For TNM8, Stage I (n = 4,556), II (n = 1,206), III (n = 598), and IV (n = 54) had an estimated 5-year MSS of 98.4%, 82.5%, 66.4%, and 14.4%, respectively. Within stage III, IIIA 5-year MSS was 91.7% while stage IIID was 23.5%. HRs indicated that TNM8 more evenly separates subgroups once adjusted for patient- and disease-characteristics. The variance in MSS explained by TNM7 and TNM8 is 18.9% and 19.7%, respectively. CONCLUSION: TNM8 performed well in our sample, with more even separation of stage subgroups and a modest improvement in predictive ability compared to TNM7.

Incident Cancer Detection During Multiple Waves of COVID-19: The Tsunami After the Earthquake.

No population-based study exists to demonstrate the full-spectrum impact of COVID-19 on hindering incident cancer detection in a large cancer system. Building upon our previous publication in JNCCN, we conducted an updated analysis using 12 months of new data accrued in the pandemic era (extending the study period from September 26, 2020, to October 2, 2021) to demonstrate how multiple COVID-19 waves affected the weekly cancer incidence volume in Ontario, Canada, and if we have fully cleared the backlog at the end of each wave.

Incident Cancer Detection During the COVID-19 Pandemic.

BACKGROUND: Resource restrictions were established in many jurisdictions to maintain health system capacity during the COVID-19 pandemic. Disrupted healthcare access likely impacted early cancer detection. The objective of this study was to assess the impact of the pandemic on weekly reported cancer incidence. PATIENTS AND METHODS: This was a population-based study involving individuals diagnosed with cancer from September 25, 2016, to September 26, 2020, in Ontario, Canada. Weekly cancer incidence counts were examined using segmented negative binomial regression models. The weekly estimated backlog during the pandemic was calculated by subtracting the observed volume from the projected/expected volume in that week. RESULTS: The cohort consisted of 358,487 adult patients with cancer. At the start of the pandemic, there was an immediate 34.3% decline in the estimated mean cancer incidence volume (relative rate, 0.66; 95% CI, 0.57-0.75), followed by a 1% increase in cancer incidence volume in each subsequent week (relative rate, 1.009; 95% CI, 1.001-1.017). Similar trends were found for both screening and nonscreening cancers. The largest immediate declines were seen for melanoma and cervical, endocrinologic, and prostate cancers. For hepatobiliary and lung cancers, there continued to be a weekly decline in incidence during the COVID-19 period. Between March 15 and September 26, 2020, 12,601 fewer individuals were diagnosed with cancer, with an estimated weekly backlog of 450. CONCLUSIONS: We estimate that there is a large volume of undetected cancer cases related to the COVID-19 pandemic. Incidence rates have not yet returned to prepandemic levels.

Defining a Core Data Set for the Economic Evaluation of Precision Oncology.

OBJECTIVES: Precision oncology is generating vast amounts of multiomic data to improve human health and accelerate research. Existing clinical study designs and attendant data are unable to provide comparative evidence for economic evaluations. This lack of evidence can cause inconsistent and inappropriate reimbursement. Our study defines a core data set to facilitate economic evaluations of precision oncology. METHODS: We conducted a literature review of economic evaluations of next-generation sequencing technologies, a common application of precision oncology, published between 2005 and 2018 and indexed in PubMed (MEDLINE). Based on this review, we developed a preliminary core data set for informal expert feedback. We then used a modified-Delphi approach with individuals involved in implementation and evaluation of precision medicine, including 2 survey rounds followed by a final voting conference to refine the data set. RESULTS: Two authors determined that variation in published data elements was reached after abstraction of 20 economic evaluations. Expert consultation refined the data set to 83 unique data elements, and a multidisciplinary sample of 46 experts participated in the modified-Delphi process. A total of 68 elements (81%) were selected as required, spanning demographics and clinical characteristics, genomic data, cancer treatment, health and quality of life outcomes, and resource use. CONCLUSIONS: Cost-effectiveness analyses will fail to reflect the real-world impacts of precision oncology without data to accurately characterize patient care trajectories and outcomes. Data collection in accordance with the proposed core data set will promote standardization and enable the generation of decision-grade evidence to inform reimbursement.

Real-world, population-based cohort study of toxicity and resource utilization of second-line ipilimumab for metastatic melanoma in Ontario, Canada.

Second-line ipilimumab has been publicly funded in Ontario for metastatic melanoma (MM) since September 2012. We examined real-world toxicity of second-line ipilimumab compared to standard second-line treatments prior to funding. MM patients who received systemic treatment from April 2005 to March 2015 were included. Patients receiving second-line ipilimumab after September 2012 were considered as cases, and those who received second-line treatment prior to the funding date were included as historical controls. Outcomes assessed include treatment-related mortality, any-cause hospital visits, ipilimumab-related hospital visits and specialist visits (eg, endocrinologists, ophthalmologists, gastroenterologists, rheumatologists and respirologists), which were captured from up to 30 and/or 90 days after end of second-line treatment. Inverse probability of treatment weighting was used to adjust for baseline differences between groups. Odds ratios (ORs) from logistic regressions and rate ratios (RRs) from rate regressions were used to assess differences between groups. We identified 329 MM patients who received second-line treatments (ipilimumab: 189; controls: 140). Ipilimumab was associated greater any-cause (60.1% vs 45.7%; OR = 1.81; P value = .019) and ipilimumab-related (47.2% vs 31.9%; OR = 1.91; P value = .011) hospital visits. Adjusting for different follow-up days, ipilimumab was associated with higher rates of all-cause (RR = 1.56 [95%CI: 1.12-2.16]), and ipilimumab-related (RR = 2.18 [95% CI: 1.45-3.27]) hospital visits. Patients receiving ipilimumab were more likely to visit specialist involved in immunotherapy toxicity management (23.5% vs 13.7%; P value = .04). Compared to historical second-line treatments, second-line ipilimumab was associated with more health service utilization (specifically hospital visits and specialist visits), suggestive of potentially increased toxicity in the real world.

Cancer staging in individuals with a severe psychiatric illness: a cross-sectional study using population-based cancer registry data.

BACKGROUND: Advanced cancer stage at diagnosis may explain high cancer mortality among patients with a severe psychiatric illness (SPI). Studies to date investigating advanced stage cancer at diagnosis as a potential explanation for high cancer mortality in individuals with a history of mental illness have been inconclusive. We examined the relationship between a SPI history and unknown cancer stage at diagnosis in colorectal cancer (CRC) patients. METHODS: This was a population-based, cross-sectional study using linked administrative databases of CRC patients diagnosed between 01/04/2007 and 31/12/2012. Individuals who had a history of mental illness but did not meet the definition of a SPI were excluded. An SPI was measured in the 5 years prior to the cancer diagnosis and categorized as inpatient, outpatient or no SPI. Individuals with a best stage in Stage 0 to Stage IV were considered staged and absence of staging information was defined as unknown stage. The risk of unknown stage cancer was estimated using modified Poisson regression. RESULTS: The final study cohort included 24,507 CRC patients. 258 (1.1%) individuals experienced a history of inpatient SPI and 482 (2.0%) experienced outpatient SPI. After adjusting for confounders, CRC patients with an inpatient or outpatient history of SPI were at greater risk of having missing TNM stage at diagnosis, compared to patients with no history of a mental illness (RR 1.45 (95% CI: 1.14-1.85) and RR1.17 (95% CI 0.95-1.43), respectively). The results did not change when alternate practices to assign SPI history using administrative data were used. CONCLUSIONS: Individuals with an SPI, especially those with a psychiatric admission, were more likely to have missing stage data compared to individuals without a history of a mental illness. Incomplete and low quality cancer staging data likely undermines the quality of cancer care following initial diagnosis. Understanding why patients with an SPI are missing this information is a critical first step to providing excellent care to this vulnerable population.

Real-world comparative effectiveness of second-line ipilimumab for metastatic melanoma: a population-based cohort study in Ontario, Canada.

BACKGROUND: For novel cancer treatments, effectiveness in clinical practice is not always aligned with clinical efficacy results. As such it is important to understand a treatment's real-world effectiveness. We examined real-world population-based comparative effectiveness of second-line ipilimumab versus non-ipilimumab treatments (chemotherapy or targeted treatments). METHODS: We used a cohort of melanoma patients receiving systemic treatment for advanced disease since April 2005 from Ontario, Canada. Patients were identified from provincial drug databases and the Ontario Cancer Registry who received second-line ipilimumab from 2012 to 2015 (treated) or second-line non-ipilimumab treatment prior to 2012 (historical controls). Historical controls were chosen, to permit the most direct comparison to pivotal trial findings. The cohort was linked to administrative databases to identify baseline characteristics and outcomes. Kaplan-Meier curves and multivariable Cox regression models were used to assess overall survival (OS). Observed potential confounders were adjusted for using inverse probability of treatment weighting (IPTW). RESULTS: We identified 329 patients with metastatic melanoma (MM) who had received second-line treatments (189 treated; 140 controls). Patients receiving second-line ipilimumab were older (61.7 years vs 55.2 years) compared to historical controls. Median OS were 6.9 (95% CI: 5.4-8.3) and 4.95 (4.3-6.0) months for ipilimumab and controls, respectively. The crude 1-year, 2-year, and 3-year OS probabilities were 34.3% (27-41%), 20.6% (15-27%), and 15.2% (9.6-21%) for ipilimumab and 17.1% (11-23%), 7.1% (2.9-11%), and 4.7% (1.2-8.2%) for controls. Ipilimumab was associated with improved OS (IPTW HR = 0.62; 95% CI: 0.49-0.78; p < 0.0001). CONCLUSIONS: This real-world analysis suggests second-line ipilimumab is associated with an improvement in OS for MM patients in routine practice.

Scale-up of radiotherapy for cervical cancer in the era of human papillomavirus vaccination in low-income and middle-income countries: a model-based analysis of need and economic impact.

BACKGROUND: Radiotherapy is standard of care for cervical cancer, but major global gaps in access exist, particularly in low-income and middle-income countries. We modelled the health and economic benefits of a 20-year radiotherapy scale-up to estimate the long-term demand for treatment in the context of human papillomavirus (HPV) vaccination. METHODS: We applied the Global Task Force on Radiotherapy for Cancer Control investment framework to model the health and economic benefits of scaling up external-beam radiotherapy and brachytherapy for cervical cancer in upper-middle-income, lower-middle-income, and low-income countries between 2015 and 2035. We estimated the unique costs of external-beam radiotherapy and brachytherapy and included a specific valuation of women's caregiving contributions. Model outcomes life-years gained and the human capital and full income net present value of investment. We estimated the effects of stage at diagnosis, radiotherapy delivery system, and simultaneous HPV vaccination (75% coverage) up to a time horizon set at 2072. FINDINGS: For the period from 2015 to 2035, we estimated that 9·4 million women in low-income and middle-income countries required treatment with external-beam radiotherapy, of which 7·0 million also required treatment with brachytherapy. Incremental scale-up of radiotherapy in these countries from 2015 to meet optimal radiotherapy demand by 2035 yielded 11·4 million life-years gained, $59·3 billion in human capital net present value (-$1·5 billion in low-income, $19·9 billion in lower-middle-income, and $40·9 billion in upper-middle-income countries), and $151·5 billion in full income net present value ($1·5 billion in low-income countries, $53·6 billion in lower-middle-income countries, and $96·4 billion in upper-middle-income countries). Benefits increased with advanced stage of cervical cancer and more efficient scale up of radiotherapy. Bivalent HPV vaccination of 12-year-old girls resulted in a 3·9% reduction in incident cases from 2015-2035. By 2072, when the first vaccinated cohort of girls reaches 70 years of age, vaccination yielded a 22·9% reduction in cervical cancer incidence, with 38·4 million requiring external-beam radiotherapy and 28·8 million requiring brachytherapy. INTERPRETATION: Effective cervical cancer control requires a comprehensive strategy. Even with HPV vaccination, radiotherapy treatment scale-up remains essential and produces large health benefits and a strong return on investment to countries at different levels of development. FUNDING: None.

Patient Indications for Mohs Micrographic Surgery: A Systematic Review.

The purpose of the present review was to describe evidence-based indications for Mohs micrographic surgery (MMS) in patients with a diagnosis of skin cancer. Relevant studies were identified from a systematic MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews search of studies published from 1970 to 2017. Randomized controlled trials (RCTs), prospective and retrospective comparative studies with greater than 30 patients, and single-arm retrospective studies with multivariate analyses were included. A total of 2 RCTs, 3 prospective studies, and 16 retrospective studies (14 comparative and 2 single-arm) were included. Data on recurrence rate, cure rate, complications, cosmesis, and quality of life were extracted. Surgery (with postoperative or intraoperative marginal assessment) or radiation for those who are ineligible for surgery should remain the standard of care for patients with skin cancer given the lack of high-quality, comparative evidence. MMS is recommended for those with histologically confirmed recurrent basal cell carcinoma (BCC) of the face and is appropriate for primary BCCs of the face that are >1 cm, have aggressive histology, or are located on the H zone of the face. The available evidence is difficult to generalize to all patients with skin cancer because the evidence did not adequately cover non-BCC skin cancers; however, those skin cancers can be considered on a case-by-case basis for MMS. MMS should be performed by physicians who have completed a degree in medicine or equivalent, including a Royal College of Physicians and Surgeons of Canada Specialist Certificate or equivalent, and have received advanced training in MMS.

Use and Effectiveness of Adjuvant Chemotherapy for Stage III Colon Cancer: A Population-Based Study.

BACKGROUND: International guidelines recommend adjuvant chemotherapy (ACT) for patients with stage III colon cancer. Whether efficacy observed in clinical trials translates to effectiveness in routine practice is less well understood. Here we describe use and outcomes of ACT in routine practice. METHODS: All cases of colon cancer treated with surgery in Ontario 2002-2008 were identified using the population-based Ontario Cancer Registry. Linked electronic records of treatment identified surgery and ACT use. Pathology reports were obtained for a random 25% sample of all cases; patients with stage III disease were included in the study population. Modified Poisson regression was used to evaluate factors associated with ACT. Cox proportional hazards model and propensity score analysis were used to explore the association between ACT and cancer-specific survival (CSS) and overall survival (OS). RESULTS: The study population included 2,801 patients with stage III colon cancer; 66% (n=1,861) received ACT. ACT use rates varied substantially across age groups; 90% among patients aged 20 to 49 years versus 68% among those aged 70 to 79 years (P<.001). ACT use was inversely associated with comorbidity (P<.001) and socioeconomic status (P=.049). In adjusted analyses advanced age is associated with inferior CSS and OS. Use of ACT was associated with decreased risk of death from cancer (hazard ratio [HR], 0.63; 95% CI, 0.54-0.73) and decreased risk of death from any cause (HR, 0.63; 95% CI, 0.55-0.71). This result was consistent in the propensity score analysis. CONCLUSIONS: One-third of patients with stage III colon cancer in the general population do not receive ACT. Use of ACT in routine practice is associated with a substantial improvement in CSS and OS.

Expanding global access to radiotherapy.

Radiotherapy is a critical and inseparable component of comprehensive cancer treatment and care. For many of the most common cancers in low-income and middle-income countries, radiotherapy is essential for effective treatment. In high-income countries, radiotherapy is used in more than half of all cases of cancer to cure localised disease, palliate symptoms, and control disease in incurable cancers. Yet, in planning and building treatment capacity for cancer, radiotherapy is frequently the last resource to be considered. Consequently, worldwide access to radiotherapy is unacceptably low. We present a new body of evidence that quantifies the worldwide coverage of radiotherapy services by country. We show the shortfall in access to radiotherapy by country and globally for 2015-35 based on current and projected need, and show substantial health and economic benefits to investing in radiotherapy. The cost of scaling up radiotherapy in the nominal model in 2015-35 is US$26·6 billion in low-income countries, $62·6 billion in lower-middle-income countries, and $94·8 billion in upper-middle-income countries, which amounts to $184·0 billion across all low-income and middle-income countries. In the efficiency model the costs were lower: $14·1 billion in low-income, $33·3 billion in lower-middle-income, and $49·4 billion in upper-middle-income countries-a total of $96·8 billion. Scale-up of radiotherapy capacity in 2015-35 from current levels could lead to saving of 26·9 million life-years in low-income and middle-income countries over the lifetime of the patients who received treatment. The economic benefits of investment in radiotherapy are very substantial. Using the nominal cost model could produce a net benefit of $278·1 billion in 2015-35 ($265·2 million in low-income countries, $38·5 billion in lower-middle-income countries, and $239·3 billion in upper-middle-income countries). Investment in the efficiency model would produce in the same period an even greater total benefit of $365·4 billion ($12·8 billion in low-income countries, $67·7 billion in lower-middle-income countries, and $284·7 billion in upper-middle-income countries). The returns, by the human-capital approach, are projected to be less with the nominal cost model, amounting to $16·9 billion in 2015-35 (-$14·9 billion in low-income countries; -$18·7 billion in lower-middle-income countries, and $50·5 billion in upper-middle-income countries). The returns with the efficiency model were projected to be greater, however, amounting to $104·2 billion (-$2·4 billion in low-income countries, $10·7 billion in lower-middle-income countries, and $95·9 billion in upper-middle-income countries). Our results provide compelling evidence that investment in radiotherapy not only enables treatment of large numbers of cancer cases to save lives, but also brings positive economic benefits.

The management of stage I Non-Small cell lung cancer (NSCLC) in Ontario: A Population-Based study of patterns of care and Stereotactic Ablative Body radiotherapy (SABR) utilization from 2010 to 2019.

BACKGROUND: Stereotactic Ablative Body Radiotherapy (SABR) is the standard of care for medically inoperable patients with Stage I NSCLC. The adoption of SABR and its association with cancer outcomes requires characterization. AIM: We described the management of biopsy-proven Stage I NSCLC with SABR, surgery, non-SABR curative radiotherapy (RT) and observation in Ontario, Canada, between 2010 and 2019. Temporal and geographic trends in practice and survival outcomes were analyzed. METHODS: This was a retrospective population-based cohort study conducted by linking electronic radiotherapy (RT) records to a population-based cancer registry. RESULTS: A total of 12,065 patients were identified, 61.7 % underwent surgery, 17.9 % received SABR, 8.6 % received non-SABR curative RT and 11.7 % were observed. Between 2010 and 2019, the utilization of surgery decreased (63.8 % to 49.9 %, p < 0.0001), while SABR use increased (7.5 % to 24.4 %, p < 0.0001), non-SABR curative RT use increased (6.7 % to 9.6 %, p < 0.0014) and patients observed decreased (14.4 % to 12.0 %, p < 0.0001). Substantial variation in practice exists across Ontario. Two- yr CSS improved for the entire cohort (81.9 % to 85.0 %, p < 0.0001). While there was improvement in 2 yr CSS for surgical patients (92.1 %% to 95.7 %, p < 0.001), survival for patients who received SABR, Non-SABR curative RT and observation remained stable. CONCLUSION: There has been an increase in SABR utilization and a reduction in surgical utilization with a corresponding increased survival of stage I patients in Ontario between 2010 and 2019. Substantial differences in practice patterns exist across health regions, suggesting the need for strategies to improve access to SABR in many jurisdictions.

Common Sense (Radiation) Oncology: Redefining targets in radiotherapy.

In 2023, the Common Sense Oncology (CSO) movement was launched with the goal of recalibrating cancer care to focus on outcomes that matter to patients. We extend the three CSO pillars - evidence generation, interpretation and communication - to radiation oncology and advocate for better evidence demonstrating the value of our modality.

Trajectories of Health Care Contact Days for Patients With Stage IV Non-Small Cell Lung Cancer.

Importance: Patients with stage IV non-small cell lung cancer (NSCLC) experience substantial morbidity and mortality. Contact days (ie, the number of days with health care contact outside the home) measure how much of a person's life is consumed by health care, yet little is known about patterns of contact days for patients with NSCLC. Objective: To describe the trajectories of contact days in patients with stage IV NSCLC and how trajectories vary by receipt of cancer-directed treatment in routine practice. Design, Setting, and Participants: A retrospective, population-based decedent cohort study was conducted in Ontario, Canada. Participants included adults aged 20 years or older who were diagnosed with stage IV NSCLC (January 1, 2014, to December 31, 2017) and died (January 1, 2014, to December 31, 2019); there was a maximum 2-year follow-up. Data analysis was conducted from February 22 to August 16, 2023. Exposure: Systemic cancer-directed therapy (yes or no) and type of therapy (chemotherapy vs immunotherapy vs targeted therapy). Main Outcomes and Measures: Contact days (days with health care contact, outpatient or institution-based, outside the home) were identified through administrative data. The weekly percentage of contact days and fitted models with cubic splines were quantified to describe trajectories from diagnosis until death. Results: A total of 5785 decedents with stage IV NSCLC were included (median age, 70 [IQR 62-77] years; 3108 [53.7%] were male, and 1985 [34.3%] received systemic therapy). The median overall survival was 108 (IQR, 49-426) days, median contact days were 36 (IQR, 21-62), and the median percentage that were contact days was 33.3%. A median of 5 (IQR, 2-10) days were spent with specialty palliative care. Patients who did not receive systemic therapy had a median overall survival of 66 (IQR, 34-130) days and median contact days of 28 (IQR, 17-44), of which a median of 5 (IQR, 2-9) days were spent with specialty palliative care. Overall and for subgroups, normalized trajectories followed a U-shaped distribution: contact days were most frequent immediately after diagnosis and before death. Patients who received targeted therapy had the lowest contact day rate during the trough (10.6%; vs immunotherapy, 15.4%; vs chemotherapy, 17.7%). Conclusions and Relevance: In this cohort study, decedents with stage IV NSCLC had a median survival in the order of 3.5 months and spent 1 in every 3 days alive interacting with the health care system outside the home. These results highlight the need to better support patients and care partners, benchmark appropriateness, and improve care delivery.

Challenges in building radiotherapy capacity: A longitudinal study evaluating eight years of the Brazilian radiotherapy expansion plan.

BACKGROUND: In 2012, the Brazilian government launched a radiotherapy (RT) expansion plan (PER-SUS) to install 100 linear accelerators. This study assesses the development of this program after eight years. METHODS: Official reports from the Ministry of Health (MoH) were reviewed. RT centres projects status, timeframes, and cost data (all converted to US dollars) were extracted. The time analysis was divided into seven phases, and for cost evaluation, there were five stages. The initial predicted project time (IPPT) and costs (estimated by the MoH) for each phase were compared between the 18 operational RT centres (able to treat patients) and 30 non-operational RT centres using t-tests, ANOVA, and the Mann-Whitney U. A p-value < 0.05 indicates statistical significance. RESULTS: A significant delay was observed when comparing the IPPT with the overall time to conclude each 48 RT centres project (p < 0.001), with considerable delays in the first five phases (p < 0.001 for all). Moreover, the median time to conclude the first 18 operational RT centres (77.4 months) was shorter compared with the 30 non-operational RT centres (94.0 months), p < 0.001. The total cost of 48 RT services was USD 82,84 millions (mi) with a significant difference in the per project median total cost between 18 operational RT centres, USD1,34 mi and 30 non-operational RT centres USD2,11 mi, p < 0.001. All phases had a higher cost when comparing 30 non-operational RT centres to 18 operational RT centres, p < 0.001. The median total cost for expanding existing RT centres was USD1,30 mi versus USD2,18 mi for new RT services, p < 0.0001. CONCLUSION: After eight years, the PER-SUS programs showed a substantial delay in most projects and their phases, with increased costs over time. POLICY SUMMARY: Our findings indicate a need to act to increase the success of this plan. This study may provide a benchmark for other developing countries trying to expand RT capacity.

Impact on costs and outcomes of multi-gene panel testing for advanced solid malignancies: a cost-consequence analysis using linked administrative data.

Background: To date, economic analyses of tissue-based next generation sequencing genomic profiling (NGS) for advanced solid tumors have typically required models with assumptions, with little real-world evidence on overall survival (OS), clinical trial enrollment or end-of-life quality of care. Methods: Cost consequence analysis of NGS testing (555 or 161-gene panels) for advanced solid tumors through the OCTANE clinical trial (NCT02906943). This is a longitudinal, propensity score-matched retrospective cohort study in Ontario, Canada using linked administrative data. Patients enrolled in OCTANE at Princess Margaret Cancer Centre from August 2016 until March 2019 were matched with contemporary patients without large gene panel testing from across Ontario not enrolled in OCTANE. Patients were matched according to 19 patient, disease and treatment variables. Full 2-year follow-up data was available. Sensitivity analyses considered alternative matched cohorts. Main Outcomes were mean per capita costs (2019 Canadian dollars) from a public payer's perspective, OS, clinical trial enrollment and end-of-life quality metrics. Findings: There were 782 OCTANE patients with 782 matched controls. Variables were balanced after matching (standardized difference <0.10). There were higher mean health-care costs with OCTANE ($79,702 vs. $59,550), mainly due to outpatient and specialist visits. Publicly funded drug costs were less with OCTANE ($20,015 vs. $24,465). OCTANE enrollment was not associated with improved OS (restricted mean survival time [standard error]: 1.50 (±0.03) vs. 1.44 (±0.03) years, log-rank p = 0.153), varying by tumor type. In five tumor types with ≥35 OCTANE patients, OS was similar in three (breast, colon, uterus, all p > 0.40), and greater in two (ovary, biliary, both p < 0.05). OCTANE was associated with greater clinical trial enrollment (25.4% vs. 9.5%, p < 0.001) and better end-of-life quality due to less death in hospital (10.2% vs. 16.4%, p = 0.003). Results were robust in sensitivity analysis. Interpretation: We found an increase in healthcare costs associated with multi-gene panel testing for advanced cancer treatment. The impact on OS was not significant, but varied across tumor types. OCTANE was associated with greater trial enrollment, lower publicly funded drug costs and fewer in-hospital deaths suggesting important considerations in determining the value of NGS panel testing for advanced cancers. Funding: T.P H holds a research grant provided by the Ontario Institute for Cancer Research through funding provided by the Government of Ontario (#IA-035 and P.HSR.158) and through funding of the Canadian Network for Learning Healthcare Systems and Cost-Effective 'Omics Innovation (CLEO) via Genome Canada (G05CHS).