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Background: The addition of induction chemotherapy to concomitant neoadjuvant chemoradiation in locally advanced rectal cancer could increase pathological downstaging and act on occult micrometastatic disease, leading ultimately to a better outcome. A systematic review was carried out of the existing literature on the treatment outcomes of total neoadjuvant therapy (TNT) on locally advanced rectal cancer. TNT was defined as chemotherapy using cycles of induction and/or consolidation in conjunction with standard chemoradiotherapy prior to surgery. Methods: A systematic search of PubMed, Embase, and the Cochrane Library was performed according to the PRISMA statement up until January 2019. The primary endpoints were complete pathologic response (pCR), disease-free survival, and overall survival rates. Results: A total of 28 studies (3 retrospective and 25 prospective for a total of 3579 patients) were included in the final analysis (n = 2688 treated with TNT and n = 891 with neoadjuvant chemoradiotherapy therapy). The pooled pCR rate was 22.4% (95% CI 19.4%-25.7%) in all patients treated with TNT (n = 27 studies with data available). In n = 10 comparative studies with data available, TNT was found to increase the odds of pCR by 39% (1.40, 95% CI 1.08-1.81, P = 0.01). Conclusions: The addition of induction or consolidation chemotherapy to standard neoadjuvant chemoradiotherapy results in a higher pCR rate. Given that the comparative analysis was derived from few randomized publications, large confirmatory trials should be carried out before a strong recommendation is made in favor of TNT. [ABSTRACT FROM AUTHOR]

One of the historical standard of care for locally advanced rectal adenocarcinoma (LARC) is neoadjuvant fluoropyrimidine-based chemoradiotherapy (FP-based CTRT) followed 6–8 weeks later by surgery. The incorporation of further chemotherapy cycles (CT) before or after CTRT (total neoadjuvant therapy) resulted in better outcomes than CTRT alone. Therefore, we performed a network meta-analysis (NMA) to compare the relative efficacy of different neoadjuvant treatments for LARC. Fixed-or random-effects models were fit using a Bayesian approach to NMA. Between-group comparisons were estimated using hazard ratios (HRs) or risk ratios (RRs) with 95 % credible intervals (95 % CrIs). A total of 23 randomized clinical trials were included. In Bayesian comparisons. FOLFIRINOX followed by capecitabine-based CTRT resulted in better OS than other regimens, including the previous standard, and ranked as the best regimen with a probability of 87 %. This NMA confirms that adopting total neoadjuvant therapy improves outcome compared to other preoperative strategies, including FP-based CTRT. [Display omitted] • This network meta-analysis found that induction FOLFIRINOX ranked as the best option in terms of overall survival for LARC. • Chemotherapy doublets following CTRT resulted as the best treatment both in terms of disease-free survival. • FOLFIRINOX followed by CTRT and (CT)RT + oxaliplatin-based CT resulted as the preferred options for LARC. • Incorporation of total neoadjuvant therapy into the LARC management is emerging as the new standard of care. [ABSTRACT FROM AUTHOR]

• There is a rationale for the combination of radiotherapy + immunotherapy (RT + IT). • We have assessed the efficacy of RT + IT for brain metastases of solid tumors. • Median pooled OS was 15.9 months in n = 30 studies with data available. • One- and 2-year OS rates were 55 and 35% respectively. • Addition of IT to RT lead to an improved OS (HR = 0.54, 95%CI 0.44–0.67; P < 0.001). Radiotherapy (RT) represents a mainstay in the treatment of brain metastases (BMs) from solid tumors. Immunotherapy (IT) has improved survival of metastatic cancer patients across many tumor types. The combination of RT and IT for the treatment of BMs has a strong rationale, but data on efficacy and safety of this combination is still limited. A systematic search of PubMed, the Cochrane Central Register of Controlled Trials, and EMBASE was conducted. 33 studies were included for a total of 1520 patients, most of them with melanoma (87%). Median pooled OS was 15.9 months (95%CI 13.9–18.1). One- and 2-year OS rates were 55.2% (95% CI 49.3–60.9) and 35.7% (95% CI 30.4–41.3), respectively. Addition of IT to RT was associated with improved OS (HR = 0.54, 95%CI 0.44-0.67; P < 0.001). For patients with BMs from solid tumors, addition of concurrent IT to brain RT is able to increase survival and provide long term control. [ABSTRACT FROM AUTHOR]

Highlights • Merkel cell carcinoma (MCC) is a cutaneous malignancy with high risk of relapse. • The main treatment is surgery plus or minus adjuvant radiotherapy (RT). • We performed a systematic review and meta-analysis of the benefits of adjuvant RT. • There was a significant increase in OS with adjuvant RT (HR = 0.81, P < 0.001). • We found that adjuvant RT may improve locoregional control and survival in MCC. Abstract Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignancy with a high propensity for local recurrence and regional and distant metastases. The main treatment is surgery with narrow excision margins and draining nodes, plus or minus adjuvant radiotherapy (RT) on the surgical bed and/or lymph nodes. We performed a systematic review and meta-analysis of the benefits of adjuvant RT in MCC treatment. PubMed, EMBASE, and the Cochrane Library were systematically searched to identify relevant studies published before September 2018. Prospective trials and retrospective series comparing adjuvant RT vs. no RT in resected primary MCCs were included. Primary endpoint was to evaluate the outcomes of MCC patients who received adjuvant RT in term of overall survival (OS) and disease-free survival (DFS). Hazard ratios (HRs) for OS and DFS were aggregated according to a fixed or random effect model. Secondary endpoints were local, locoregional, and distant DFS. A total of 17,179 MCCs across 29 studies were analysed. There was a significant difference in OS between the RT and no RT arms (HR = 0.81, 95%CI 0.75–0.86, P < 0.001). There was also a significant difference in DFS in favour of adjuvant RT (HR = 0.45, 95%CI 0.32–0.62, P < 0.001). Adjuvant RT improved locoregional DFS and local DFS but not distant DFS (HR = 0.3, 95%CI 0.22–0.42; HR = 0.21, 95%CI 0.14–0.33, and HR = 0.79, 95%CI 0.49–1.14, respectively). Meta-regression analysis showed that high Newcastle–Ottawa scale scores, stage I–II MCCs, shorter follow-up durations, size >2 cm, and being of a younger age were associated with increased OS. This systematic review and meta-analysis suggests a survival and DFS benefit for postoperative radiation of MCCs. Intermediate stage MCCs derive the maximum benefit with local and regional relapses reduced by 80% and 70%, respectively. Conversely, distant metastases were not significantly prevented. [ABSTRACT FROM AUTHOR]

Highlights • Oligometastatic NSCLC has few distant lesions that can be amenable to treatment. • We evaluated if RT to the primary tumor improves outcome in oligometastatic NSCLC. • Among 21 studies overall survival was improved with the addition of thoracic RT (HR = 0.44, 95%CI 0.32-0.6). • RT added to the primary tumour increased PFS (HR = 0.42, 95%CI 0.33-0.55; P < 0.001). • In oligometastatic NSCLC, RT to the primary tumour is associated with better survival. Abstract Oligometastatic non-small cell lung cancer (NSCLC) has a discrete number of distant lesions (<5) that can be amenable to radical treatment. The treatment of the primary lung tumour in such stage IV cases is still debated. We conducted a systematic review and meta-analysis to evaluate the outcome of these patients and the added benefit in terms of overall survival (OS) and progression-free survival (PFS) when radical treatment of the primary tumour with radiotherapy (RT) was delivered. PubMed, EMBASE and Cochrane Library were systematically searched to identify relevant studies published up to July 2018. Prospective trials and retrospective series comparing RT vs no RT to the primary NSCLC in the presence of oligometastases were included. Hazard ratios (HRs) for OS and PFS were aggregated according to a fixed or random effect model. Twenty-one studies for a total of 924 synchronous oligometastatic NSCLC were analysed. Median OS and PFS were 20.4 and 12 months. Pooled 1-2-3 and 5-year OS were 70.3%, 43.5%, 29.3% and 20.2% respectively. Overall survival was improved with the addition of thoracic RT (HR = 0.44, 95%CI 0.32-0.6; P < 0.001). Similarly, RT added to the primary tumour increased PFS (HR = 0.42, 95%CI 0.33-0.55; P < 0.001). The only variable associated with the median OS was the year of publication with most recent series associated with a better outcome. In patients with oligometastatic NSCLC and disease controlled with ablative therapy of distant metastases, a consolidation with radical RT to the primary tumour is associated with better survival and could be considered as a treatment modality in selected cases. [ABSTRACT FROM AUTHOR]