To quantify the association of cancer treatment delay and mortality for each four week increase in delay to inform cancer treatment pathways.
Systematic review and meta-analysis.
Published studies in ...Medline from 1 January 2000 to 10 April 2020.
Curative, neoadjuvant, and adjuvant indications for surgery, systemic treatment, or radiotherapy for cancers of the bladder, breast, colon, rectum, lung, cervix, and head and neck were included. The main outcome measure was the hazard ratio for overall survival for each four week delay for each indication. Delay was measured from diagnosis to first treatment, or from the completion of one treatment to the start of the next. The primary analysis only included high validity studies controlling for major prognostic factors. Hazard ratios were assumed to be log linear in relation to overall survival and were converted to an effect for each four week delay. Pooled effects were estimated using DerSimonian and Laird random effect models.
The review included 34 studies for 17 indications (n=1 272 681 patients). No high validity data were found for five of the radiotherapy indications or for cervical cancer surgery. The association between delay and increased mortality was significant (P<0.05) for 13 of 17 indications. Surgery findings were consistent, with a mortality risk for each four week delay of 1.06-1.08 (eg, colectomy 1.06, 95% confidence interval 1.01 to 1.12; breast surgery 1.08, 1.03 to 1.13). Estimates for systemic treatment varied (hazard ratio range 1.01-1.28). Radiotherapy estimates were for radical radiotherapy for head and neck cancer (hazard ratio 1.09, 95% confidence interval 1.05 to 1.14), adjuvant radiotherapy after breast conserving surgery (0.98, 0.88 to 1.09), and cervix cancer adjuvant radiotherapy (1.23, 1.00 to 1.50). A sensitivity analysis of studies that had been excluded because of lack of information on comorbidities or functional status did not change the findings.
Cancer treatment delay is a problem in health systems worldwide. The impact of delay on mortality can now be quantified for prioritisation and modelling. Even a four week delay of cancer treatment is associated with increased mortality across surgical, systemic treatment, and radiotherapy indications for seven cancers. Policies focused on minimising system level delays to cancer treatment initiation could improve population level survival outcomes.
Abstract
Background
Patients undergoing treatment for cancer are at increased risk of acute kidney injury (AKI). There are few data on AKI incidence and risk factors in the current era of cancer ...treatment.
Methods
We conducted a population-based study of all patients initiating systemic therapy (chemotherapy or targeted agents) for a new cancer diagnosis in Ontario, Canada (2007–2014). The primary outcome was hospitalization with AKI or acute dialysis. We estimated the cumulative incidence of AKI and fitted Fine and Gray models, adjusting for demographics, cancer characteristics, comorbidities, and coprescriptions. We modeled exposure to systemic therapy (the 90-day period following treatments) as a time-varying covariate. We also assessed temporal trends in annual AKI incidence.
Results
We identified 163 071 patients initiating systemic therapy of whom 10 880 experienced AKI. The rate of AKI was 27 per 1000 person-years, with overall cumulative incidence of 9.3% (95% CI = 9.1% to 9.6%). Malignancies with the highest 5-year AKI incidence were myeloma (26.0%, 95% CI = 24.4% to 27.7%), bladder (19.0%, 95% CI = 17.6% to 20.5%), and leukemia (15.4%, 95% CI = 14.3% to 16.5%). Advanced cancer stage, chronic kidney disease, and diabetes were associated with increased risk of AKI (adjusted hazard ratios aHR = 1.41, 95% CI = 1.28 to 1.54; 1.80, 95% CI = 1.67 to 1.93; and 1.43, 95% CI = 1.37 to 1.50, respectively). In patients aged 66 years or older with universal drug benefits, diuretic, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker coprescription was associated with higher AKI risk (aHR = 1.20, 95% CI = 1.14 to 1.28; 1.30, 95% CI = 1.23 to 1.38). AKI risk was further accentuated during the 90-day period following systemic therapy (aHR = 2.34, 95% CI = 2.24 to 2.45). The annual incidence of AKI increased from 18 to 52 per 1000 person-years between 2007 and 2014.
Conclusion
Cancer-related AKI is common and associated with advanced stage, chronic kidney disease, diabetes, and concomitant receipt of diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Risk is heightened in the 90 days after systemic therapy. Preventive strategies are needed to address the increasing burden of AKI in this population.
...the drug nab-paclitaxel (brand name abraxane) costs 50 times more per dose than paclitaxel.7 The proposed benefit of abraxane over paclitaxel is a lesser frequency of neuropathy and probably ...infusion reactions, but several cancer types are still being treated with paclitaxel as the standard of care and the minor differences in some side-effects do not justify the price difference between paclitaxel and abraxane. In 2016, the NAPOLI-1 trial tested fluorouracil plus nanoliposomal irinotecan versus fluorouracil as second-line treatment in patients who had progressed on gemcitabine-based first-line therapy (but were irinotecan naive).8 Again, nanoliposomal irinotecan is effectively just expensive irinotecan. Since FOLFIRINOX is active in pancreatic cancer, it is understandable that irinotecan would be an active agent in pancreatic cancer. ...this trial concluded that although there was no statistically significant overall survival benefit observed, “the hazard ratio numerically favored olaparib”.11 At the 2023 ASCO Gastrointestinal Cancers Symposium, the results of NAPOLI-3 trial were presented.12 This randomised controlled trial assigned patients with advanced pancreatic cancer to receive first-line NALIRIFOX (nanoliposomal irinotecan, fluorouracil, folinic acid, and oxaliplatin) or gemcitabine plus nab-paclitaxel. ...if we look at the past 25 years of treatments for metastatic pancreatic cancer, we arrive at a very sobering picture. ...we shifted towards a normalisation of progression-free survival as the primary endpoint in pancreatic cancer trials
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