***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE Clinical trials have failed to demonstrate a survival benefit of adjuvant chemotherapy in diffuse intrinsic pontine gliomas ( DIPG ) .  Radiation therapy ( RT ) is the only effective treatment thus far and reirradiation ( rRT ) has become an option at the time of progression . The aim of this study was to review the Canadian experience of DIPG rRT with a focus on the safety and possible efficacy of this approach . METHOD We retrospectively review ed the demographic , clinical , and RT data of patients with DIPG treated in Canada with rRT .  RESULTS Since January 2011 , we identified 16 patients with progressive DIPG who received rRT .  Median time from diagnosis to progression was 10.5 months ( range , 4 - 37 months ) . rRT was given focally in 14 patients at a dose ranging from 21.6 to 36 Gy . rRT was well tolerated by all children but one . All but three patients showed neurological improvement . With a median follow-up from original diagnosis of 19.2 months , all patients died , with a median time from rRT to death of 6.48 months ( range , 3.83 - 13.26 months ) . When compared to a historic cohort of 46 consecutive patients , the median time from progression to death was 92 days in the non-reirradiated patients versus 218 days in the reirradiated ones ( P = 0.0001 ) . CONCLUSION In this limited experience , rRT was safe and feasible in patients with progressive DIPG , providing neurological improvement and a prolonged life span in most patients . Prospect i ve Canadian rRT protocol s are ongoing to further assess the benefit of this approach , including quality of life assessment Diffuse intrinsic pontine glioma ( DIPG ) is a rare and deadly childhood malignancy . After 40 years of mostly single-center , often non-r and omized trials with variable patient inclusion s , there has been no improvement in survival . It is therefore time for international collaboration in DIPG research , to provide new hope for children , parents and medical professionals fighting DIPG . In a first step towards collaboration , in 2011 , a network of biologists and clinicians working in the field of DIPG was established within the European Society for Paediatric Oncology ( SIOPE ) Brain Tumour Group : the SIOPE DIPG Network . By bringing together biomedical professionals and parents as patient representatives , several collaborative DIPG-related projects have been realized . With help from experts in the fields of information technology , and legal advisors , an international , web-based comprehensive data base was developed , The SIOPE DIPG Registry and Imaging Repository , to central ly collect data of DIPG patients . As for April 2016 , clinical data as well as MR-scans of 694 patients have been entered into the SIOPE DIPG Registry/Imaging Repository . The median progression free survival is 6.0 months ( 95 % Confidence Interval ( CI ) 5.6–6.4 months ) and the median overall survival is 11.0 months ( 95 % CI 10.5–11.5 months ) . At two and five years post-diagnosis , 10 and 2 % of patients are alive , respectively . The establishment of the SIOPE DIPG Network and SIOPE DIPG Registry means a paradigm shift towards collaborative research into DIPG . This is seen as an essential first step towards underst and ing the disease , improving care and ( ultimately ) cure for children with DIPG PURPOSE To present outcome data in a prospect i ve study of radiotherapy ( RT ) with concurrent and adjuvant temozolomide ( TMZ ) in children with diffuse intrinsic pontine gliomas ( DIPGs ) . METHODS AND MATERIAL S Pediatric patients with newly diagnosed DIPGs were prospect ively treated with focal RT to a dose of 54 Gy in 30 fractions along with concurrent daily TMZ ( 75 mg/m(2 ) , Days 1 - 42 ) . Four weeks after completing the initial RT-TMZ schedule , adjuvant TMZ ( 200 mg/m(2 ) , Days 1 - 5 ) was given every 28 days to a maximum of 12 cycles . Response was evaluated clinical ly and radiologically with magnetic resonance imaging and positron emission tomography scans . RESULTS Between March 2005 and November 2006 , 20 children ( mean age , 8.3 years ) were accrued . Eighteen patients have died from disease progression , one patient is alive with progressive disease , and one patient is alive with stable disease . Median overall survival and progression-free survival were 9.15 months and 6.9 months , respectively . Grade III/IV toxicity during the concurrent RT-TMZ phase included thrombocytopenia in 3 patients , leucopenia in 2 , and vomiting in 7 . Transient Grade II skin toxicity developed in the irradiated fields in 18 patients . During the adjuvant TMZ phase , Grade III/IV leucopenia developed in 2 patients and Grade IV thrombocytopenia in 1 patient . Patients with magnetic resonance imaging diagnosis of a high- grade tumor had worse survival than those with a low- grade tumor ( p = 0.001 ) . Patients with neurologic improvement after RT-TMZ had significantly better survival than those who did not ( p = 0.048 ) . CONCLUSIONS TMZ with RT has not yielded any improvement in the outcome of DIPG compared with RT alone . Further clinical trials should explore novel treatment modalities Radiotherapy is the only treatment definitely indicated for diffuse pontine gliomas ( DIPG ) . Findings on the role of EGFR signaling in the onset of childhood DIPG prompted the use of nimotuzumab , an anti-EGFR monoclonal antibody . Assuming a potential synergy with both radiotherapy and vinorelbine , a pilot phase 2 protocol was launched that combined nimotuzumab with concomitant radiation and vinorelbine . An amendment in July 2011 introduced re-irradiation at relapse . The primary endpoint for first-line treatment was objective response rate ( CR + PR + SD ) according to the RECIST . This report concerns the outcome of this strategy as a whole . Vinorelbine 20 mg/m2 was administered weekly , with nimotuzumab 150 mg/m2 in the first 12 weeks of treatment ; radiotherapy was delivered from weeks 3 to 9 , for a total dose of 54 Gy . Vinorelbine 25 mg/m2 and nimotuzumab were given every other week thereafter until the tumor progressed or for up to 2 years . Re-irradiation consisted of 19.8 Gy , fractionated over 11 days . Baseline and latest MRIs were assessed blindly by an outside neuroradiologist . Twenty five children ( mean age 7.4 years ) were enrolled as of August 2009 ( median follow-up 29 months ) . A response was observed in 24/25 patients ( 96 % ) . The nimotuzumab/vinorelbine combination was very well tolerated , with no acute side-effects . Eleven of 16 locally-relapsing patients were re-irradiated . One-year PFS and OS rates were 30 ± 10 % and 76 ± 9 % , respectively ; 2-year OS was 27 ± 9 % ; the median PFS and OS were 8.5 and 15 months , respectively . This strategy generated interesting results and warrants further investigation Background Diffuse intrinsic pontine glioma ( DIPG ) is a rare , aggressive brain tumor with no known cure . Reirradiation ( reRT ) at recurrence can prolong survival . The impact of irradiation may be heightened when combined with PD-1 inhibition . We describe our experience using reRT , with or without PD-1 inhibition , in a cohort of patients with recurrent DIPG . Methods We performed a retrospective cohort analysis of children who received reRT with or without concomitant PD-1 inhibition for recurrent DIPG at a single institution between 2005 and 2016 . We compared progression-free ( PFS ) and overall survival ( OS ) between those who received reRT alone or in combination with PD-1 inhibition . We then compared reRT to a cohort of patients who did not receive reRT . Results Thirty-one patients were included ( 8—reRT with nivolumab ; 4—reRT alone ; 19—no reRT ) . Patients who received reRT had prolonged OS compared to no reRT ( 22.9 months — reRT with nivolumab ; 20.4 months — reRT alone ; 8.3 months — no reRT ; p < 0.0001 ) . Patients who received reRT with nivolumab vs. reRT only had slightly prolonged OS from diagnosis and from reRT ( 22.9 vs. 20.4 months for time from diagnosis ; 6.8 vs. 6.0 months for time from reRT ) . All patients receiving reRT with or without nivolumab tolerated the therapy without acute or late toxicity . Conclusions Our experience demonstrates the tolerability of reRT with concurrent PD-1 inhibition for recurrent DIPG and suggests that combination therapy may offer survival benefit . Future prospect i ve studies are needed to confirm the benefits of this combination therapy 
    Output:
    
Conclusions Based on these results , the clinical consequences of reRT for DIPG when administered appropriately and safely at first progression appear acceptable , and potentially favorable , based on the limited evidence in the current literature .
Concerns regarding acute serious toxicity were not realized .