Periodic Reporting for period 2 - ISAC (International Study on Age-related disparity in Cancer patient survival)
Berichtszeitraum: 2020-07-22 bis 2021-07-21
Survival in patients with cancer has considerably improved, except for older adults. The ISAC project aimed to investigate the role of comorbidities and other factors in cancer survival disparities among older patients compared with younger patients, which will aid interventions to increase the probability of survival regardless of age.
Specifically, the project aimed at:
1 - Determining the contribution of comorbidities, treatment and stage at diagnosis on age-related disparities in colon and lung cancer survival in New Zealand and England;
2 - Determining the effect of social determinants notably socioeconomic position and ethnicity on age-related disparities in colon and lung cancer survival in New Zealand and England;
3 - Assessing the impact of eliminating age inequalities on colon and lung cancer survival to help inform health policymakers in England.
In conclusion, age-related disparities in cancer survival are largely influenced by the stage of the disease at diagnosis and differently based on the cancer prognosis suggesting the importance of early diagnosis and individualization of cancer management in the reduction of age-related disparities in cancer survival.
Specifically, the project aimed at:
1 - Determining the contribution of comorbidities, treatment and stage at diagnosis on age-related disparities in colon and lung cancer survival in New Zealand and England;
2 - Determining the effect of social determinants notably socioeconomic position and ethnicity on age-related disparities in colon and lung cancer survival in New Zealand and England;
3 - Assessing the impact of eliminating age inequalities on colon and lung cancer survival to help inform health policymakers in England.
In conclusion, age-related disparities in cancer survival are largely influenced by the stage of the disease at diagnosis and differently based on the cancer prognosis suggesting the importance of early diagnosis and individualization of cancer management in the reduction of age-related disparities in cancer survival.
In New Zealand, the fellow reviewed the literature on factors of age-related disparities in colon and lung cancer survival and found that while age is one of the most important prognostic factors, age-related disparities in colon and lung cancer survival have so far been understudied in population-based research. Moreover, the included studies were highly heterogeneous and often of poor quality. The magnitude of age disparities in survival varied greatly by sex, ethnicity, socio-economic status, stage at diagnosis, cancer site, and morphology, the number of nodes examined, and treatment strategy. Although results were inconsistent for most characteristics, we consistently observed greater age disparities for females with lung cancer compared to males. Also, age disparities increased with more advanced disease for colon cancer and decreased with more advanced disease for lung cancer. This work is published in BMJ Open.
The fellow described the role of patient-related and clinical factors on age-related disparities in colon cancer survival among patients aged 50-99 years at diagnosis in New Zealand. The excess mortality in older patients was minimal for localized cancers, maximal during the first six months for regional cancers, the first 18 months for distant cancers, and over the three years for missing stages. Overall, the results showed that factors reflecting timeliness of cancer diagnosis (eg. stage at diagnosis and emergency diagnosis) affected the most age-related disparities in cancer survival, probably by impacting treatment strategy. This work is published in the Journal of Geriatric Oncology.
The fellow did similar work on lung cancer. In contrast to colon cancer, age-related disparities decreased as the disease was more advanced. We also observed a greater disparity in cancer survival in females compared to males, likely explained by the role of sex hormones but this needs to be confirmed. Like in colon cancer, comorbidity and socio-demographic played a minor or even no role in age-related disparity in lung cancer survival. This work is published in Lung cancer.
The Fellow presented these works at the NCRI virtual conference in November 2020, the Nuffield Department of Population Health symposium at the University of Oxford in March 2021, the SIOG 2021 virtual annual conference, and at 3 webinars (Canada, New Zealand and SIOG NAH webinar).
In England, the Fellow focused on describing treatment patterns and outcomes in relation to age.
Observational data are often used to study the effectiveness of treatment but these data are prone to several biases including the immortal time bias (ITB). ITB occurs in longitudinal studies (e.g. cohort studies, time-to-event studies) when the exposure is defined based on information available after the start of participants' follow-up. Using simulated data, we compared estimates from a time-fixed exposure model to three methods addressing ITB: time-varying exposure, delayed entry, and landmark methods, and we estimated the effect of surgery performed within 6 months of diagnosis on one-year overall survival in patients diagnosed with stage IV colon cancer aged 50-74 and separately, in those aged 75-99. In simulations, the magnitude of ITB is larger among older patients when their probability of early death increases, or the treatment is delayed. The bias is corrected using appropriate methods. In real data, appropriate methods yielded smaller effects of surgery than the time-fixed exposure approach, but effects were generally similar in both age groups. While ITB may be exacerbated in older patients, this was not obvious in our real data, because of the possible highly selected older population. The manuscript is circulating among co-authors.
The Fellow also described the patterns of chemotherapy use and associated outcomes in >18 000 patients with stage III or IV non-small cell lung cancer (NSCLC) and >8000 patients with stage III or IV small cell lung cancer (SCL) in relation to age using the national Systemic Anti-Cancer Treatment dataset. In NSCLC, the treatment plan was modified more often in patients aged 75+ than younger ones. The difference in survival based on age was small, except for patients with stage IV NSCLC who first received curative treatment.
In SCLC, despite a similar chemotherapy pattern in patients aged below 75 and older ones, the 30-day mortality rate (in stage IV SCLC) and overall survival were poorer in older patients.
Two manuscripts are in preparation and will be submitted in 2022. These results were presented at the SIOG 2021 virtual conference and the Fellow was awarded the SIOG Nursing and Allied Health investigator award for her work on NSCLC.
The Fellow could not answer the 3rd specific objective because the relevant data were not accessible for use in this project.
The Fellow was invited by the Union for International Cancer Control (UICC), a NGO advocating for better cancer control, as an expert in epidemiology of cancer in older people.
The fellow described the role of patient-related and clinical factors on age-related disparities in colon cancer survival among patients aged 50-99 years at diagnosis in New Zealand. The excess mortality in older patients was minimal for localized cancers, maximal during the first six months for regional cancers, the first 18 months for distant cancers, and over the three years for missing stages. Overall, the results showed that factors reflecting timeliness of cancer diagnosis (eg. stage at diagnosis and emergency diagnosis) affected the most age-related disparities in cancer survival, probably by impacting treatment strategy. This work is published in the Journal of Geriatric Oncology.
The fellow did similar work on lung cancer. In contrast to colon cancer, age-related disparities decreased as the disease was more advanced. We also observed a greater disparity in cancer survival in females compared to males, likely explained by the role of sex hormones but this needs to be confirmed. Like in colon cancer, comorbidity and socio-demographic played a minor or even no role in age-related disparity in lung cancer survival. This work is published in Lung cancer.
The Fellow presented these works at the NCRI virtual conference in November 2020, the Nuffield Department of Population Health symposium at the University of Oxford in March 2021, the SIOG 2021 virtual annual conference, and at 3 webinars (Canada, New Zealand and SIOG NAH webinar).
In England, the Fellow focused on describing treatment patterns and outcomes in relation to age.
Observational data are often used to study the effectiveness of treatment but these data are prone to several biases including the immortal time bias (ITB). ITB occurs in longitudinal studies (e.g. cohort studies, time-to-event studies) when the exposure is defined based on information available after the start of participants' follow-up. Using simulated data, we compared estimates from a time-fixed exposure model to three methods addressing ITB: time-varying exposure, delayed entry, and landmark methods, and we estimated the effect of surgery performed within 6 months of diagnosis on one-year overall survival in patients diagnosed with stage IV colon cancer aged 50-74 and separately, in those aged 75-99. In simulations, the magnitude of ITB is larger among older patients when their probability of early death increases, or the treatment is delayed. The bias is corrected using appropriate methods. In real data, appropriate methods yielded smaller effects of surgery than the time-fixed exposure approach, but effects were generally similar in both age groups. While ITB may be exacerbated in older patients, this was not obvious in our real data, because of the possible highly selected older population. The manuscript is circulating among co-authors.
The Fellow also described the patterns of chemotherapy use and associated outcomes in >18 000 patients with stage III or IV non-small cell lung cancer (NSCLC) and >8000 patients with stage III or IV small cell lung cancer (SCL) in relation to age using the national Systemic Anti-Cancer Treatment dataset. In NSCLC, the treatment plan was modified more often in patients aged 75+ than younger ones. The difference in survival based on age was small, except for patients with stage IV NSCLC who first received curative treatment.
In SCLC, despite a similar chemotherapy pattern in patients aged below 75 and older ones, the 30-day mortality rate (in stage IV SCLC) and overall survival were poorer in older patients.
Two manuscripts are in preparation and will be submitted in 2022. These results were presented at the SIOG 2021 virtual conference and the Fellow was awarded the SIOG Nursing and Allied Health investigator award for her work on NSCLC.
The Fellow could not answer the 3rd specific objective because the relevant data were not accessible for use in this project.
The Fellow was invited by the Union for International Cancer Control (UICC), a NGO advocating for better cancer control, as an expert in epidemiology of cancer in older people.
The ISAC project offers a comprehensive description of age disparities in survival for colon and lung cancers, two common cancers in older patients. In addition, the ISAC project described treatment patterns and outcomes in relation to age. The findings of the ISAC project identified key moments where disparities arise and started to provide evidence on cancer management that is lacking in older adults. By specifically documenting age-related disparities in cancer outcomes, the ISAC project is expected to participate in reducing the survival gap between older and younger patients.
The ISAC project does not expect any socioeconomic impacts at short or long term.
Age inequalities in cancer outcomes has attracted the attention of the International Cancer Benchmarking Partnership (ICBP) that is a collaboration bringing together clinicians, policymakers, researchers and data experts across the world. The ICBP help identify best international practice, and generate insights needed for policy and practice change. The ICBP group has invited the Fellow to be co-chair of a network of age inequalities. It is therefore likely that the Fellow's work, initiated during her Fellowship, will help improving cancer outcomes in older adults in a near future.
The ISAC project does not expect any socioeconomic impacts at short or long term.
Age inequalities in cancer outcomes has attracted the attention of the International Cancer Benchmarking Partnership (ICBP) that is a collaboration bringing together clinicians, policymakers, researchers and data experts across the world. The ICBP help identify best international practice, and generate insights needed for policy and practice change. The ICBP group has invited the Fellow to be co-chair of a network of age inequalities. It is therefore likely that the Fellow's work, initiated during her Fellowship, will help improving cancer outcomes in older adults in a near future.