Impact of Waiting Times on Mortality in Advanced Stage Non-Small Cell Lung Cancer: A 10-Year Retrospective Cohort Study in Thailand.

OBJECTIVE: This study investigated the relationship between mortality and waiting times from diagnosis to first treatment while also considering other important risk factors associated with mortality. METHODS: This is a cohort study including 497 patients diagnosed with advanced stage non-small cell lung cancer (NSCLC) between 1st January 2012 and 31st December 2021. The risk factors and waiting periods were analysed to determine their association with mortality. The waiting periods were recorded based on the timeline of patient visits, including the time between the 1st visit and imaging, the time between the 1st visit and tissue diagnosis, the time between the procedure and tissue diagnosis, the time between tissue diagnosis and treatment and the time from the 1st visit until treatment. The data were assessed using Cox regression with time-varying covariates. RESULTS: Waiting time for tissue diagnosis had a modest effect on mortality, a waiting time of more than four weeks indicated poor prognosis both in univariate and multivariate analyses [HR 1.48 (95%CI 1.18-1.87), p = < 0.01), adjusted HR 1.007 (95%CI 1.002-1.010), p = 0.02]. Waiting time for other services was not shown to be associated with mortality. The mortality rate was 3 times higher in patients with poor ECOG performance status than good ECOG performance [adjusted HR 3.17(2.04-4.91)]. Patients with EGFR sensitizing mutation who were treated with EGFR TKI therapy had a lower risk of lung cancer death compared to those being treated with chemotherapy [adjusted HR 0.49 (0.33-0.72)]. CONCLUSION: Molecular testing for EGFR sensitizing mutation and the TKI treatment were fundamental changes that assisted in improving survival rates for patients diagnosed with advanced stage lung cancer over the 10-year period. However, poor ECOG performance status remained a strong risk factor for lung cancer death. Longer waiting time for tissue diagnosis might indicate a poor prognosis.

Tumor stage affects risk and prognosis of contralateral breast cancer: results from a large Swedish-population-based study.

PURPOSE: The number of breast cancer survivors at risk of developing contralateral breast cancer (CBC) is increasing. However, ambiguity remains regarding risk factors and prognosis for women with CBC. PATIENTS AND METHODS: In a cohort of 42,670 women with breast cancer in the Uppsala/Örebro and Stockholm regions in Sweden in 1992 to 2008, we assessed risk factors for and prognosis of metachronous CBC by using survival analysis. Breast cancer-specific survival for women with CBC was evaluated and compared with results for women with unilateral breast cancer (UBC) by using time-dependent Cox-regression modeling. RESULTS: An increased risk for CBC was observed among women who had primary breast cancer with ≥ 10 involved lymph nodes compared with node-negative women (adjusted hazard ratio [HR], 1.8; 95% CI, 1.2 to 2.7). The prognosis was poorer in women with CBC than with UBC. The hazard of dying from breast cancer was especially high for women with a short interval time to CBC (adjusted HR, 2.3; 95% CI, 1.8 to 2.8 for CBC diagnosed ≤ 5 years v UBC) and gradually decreased with longer follow-up time but remained higher than the hazard originating from the primary tumor for ≥ 10 years. CONCLUSION: Women with advanced-stage primary breast cancer had an increased risk of developing CBC. CBC is associated with an increased risk of dying from breast cancer throughout a long period of follow-up after the primary tumor. Our findings suggest that the event of CBC marks a new clinical situation in terms of investigations for metastases, treatment considerations, and follow-up strategy.

Prognosis of metachronous contralateral breast cancer: importance of stage, age and interval time between the two diagnoses.

Studies comparing the prognosis after contralateral breast cancer (CBC) with that after unilateral breast cancer (UBC) shows conflicting results. We assessed the risk of breast cancer-specific death for women with metachronous CBC compared to those with a UBC in 8,478 women with invasive primary breast cancer registered in the Guy's and St. Thomas' Breast Cancer Tissue and Data Bank. Risk factors associated with breast cancer-specific death for women with CBC were estimated using Cox proportional hazards modelling. Prognoses after UBC and CBC were compared, with survival time for women with CBC calculated: (i) from CBC, (ii) from the initial cancer with CBC as a time-dependent covariate. Women diagnosed with CBC within 5 years after the initial primary breast cancer had a worse prognosis than those with CBC after 5 years and those with UBC. Women with CBC who had positive lymph nodes at the initial breast cancer diagnosis were at an increased risk of dying from breast cancer compared to those without [HR 2.5 (95% CI 1.5-4.0)]. For all stages of the initial breast cancer, a worse prognosis was observed after CBC. CBC increased the hazard originating from the initial cancer at any follow-up time, but the highest hazards were associated with a short interval to CBC. Metachronous CBC adds to the risk of dying from breast cancer. The risk increases substantially when it occurs shortly after the initial cancer, indicating a CBC in some instances may be an indicator of active distant disease. The occurrence of CBC implies a new surveillance and therapeutic situation.

Risk factors for metachronous contralateral breast cancer suggest two aetiological pathways.

Although many studies show an increased risk of metachronous contralateral breast cancer (CBC) in women with a positive family history and young age at diagnosis of the initial breast cancer, the aetiological pathways are still enigmatic. In a cohort of 8478 primary breast cancer patients diagnosed between 1975 and 2006, 558 cases of metachronous CBC were identified. Using multivariate Cox proportional hazards models, we analysed risk factors assessed at the time of the first primary tumour, including patient demographics, tumour characteristics and treatment among 4681 breast cancer patients for whom data on key variables were available. The analysis was performed separately in patients who developed CBC without and with prior recurrence(s). Risk of CBC without prior recurrent disease was increased by a positive family history [adjusted relative risk (RR) 2.8 (95% confidence interval (CI) 1.4-5.5)]; and decreased by endocrine treatment [RR 0.6 (95% CI 0.4-1.0)]. We found an increased risk of CBC with prior recurrent disease with younger age [RR 1.2 (95% CI 1.4-3.0)]; positive family history [RR 2.1 (95%CI 0.8-5.0)]; and extensive lymph node involvement [RR 2.0 (95% CI 1.2-3.6)]. Our results suggest that nodal status of the primary tumour may be as important a risk factor as family history or age, which indicates a high susceptibility to breast cancer or an impaired host defence mechanism. It may also imply that some CBCs are metastases from the first primary tumour, particularly in patients who present with recurrent disease before CBC.