Objective To quantify the association of cancer treatment delay and mortality for each four week increase in delay to inform cancer treatment pathways. Design Systematic review and meta-analysis. Data sources Published studies in Medline from 1 January 2000 to 10 April 2020. Eligibility criteria for selecting studies 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. Results 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. Conclusions 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.

The introduction of the FOLFIRINOX regimen within the last decade marked the first progress in the clinical field of metastatic pancreatic cancer which had not seen any improvements in treatment availability for several years. In a phase III randomized clinical trial, FOLFIRINOX showed superior efficacy compared to the previous standard treatment of gemcitabine monotherapy. Nevertheless, it is unknown whether the superior results observed in this single phase III clinical trial can be translated more broadly to clinical practice. Our investigation sought to analyze all published evidence of the FOLFIRINOX regimen in series and phase II trials and compare it to the experience of the phase III study. Survival analysis revealed that FOLFIRINOX was associated with an Overall Survival of 10–11 months both in the trials and in off-trial settings, with response rates also similar in both settings. The adverse effect profile was consistent between the pooled phase II and off-trial experience and the FOLFIRINOX regimen arm observed in the randomized phase III trial.

Objective/Background: The Oncotype Dx test is a genomic test currently used in clinical practice to predict the risk of disease recurrence in estrogen receptor (ER)-positive, HER2-negative breast cancer patients with axillary lymph node-negative or micrometastatic disease. The test is one of several similar genomically based tests available. Although it has a good predictive value, it is expensive and thus constitutes a significant financial burden for health systems. Thus, several attempts have been made to devise low-cost tools that could predict the recurrence score derived from the genomic evaluation using easily obtainable clinical parameters. Methods: Two previously proposed predictive tools were evaluated in a cohort of 201 patients that had undergone the Oncotype Dx test for their efficacy in predicting the Oncotype Dx Recurrence Score (RS). A simple predictor, named GR-PR, based on two available pathologic parameters, grade and progesterone receptor status was devised and also evaluated. Results: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of all three tools were compared and found to be similar for all cutoff points of Oncotype Dx RS. The accuracy of GR-PR was comparable to the best performing of the two other prediction tools for all four cutoff points. Conclusion: The simple GR-PR predictor proposed in this study seems to be at least as accurate as more complex tools and should be the preferred tool for the prediction of Oncotype Dx RS from clinicopathologic parameters when the Oncotype Dx test is not available.

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