***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: PURPOSE To evaluate the safety , efficacy and biomarkers of short-course proton beam radiation and capecitabine , followed by pancreaticoduodenectomy in a phase 1/2 study in pancreatic ductal adenocarcinoma ( PDAC ) patients . METHODS AND MATERIAL S Patients with radiographically resectable , biopsy-proven PDAC were treated with neoadjuvant short-course ( 2-week ) proton-based radiation with capecitabine , followed by surgery and adjuvant gemcitabine . The primary objective was to demonstrate a rate of toxicity grade ≥ 3 of < 20 % . Exploratory biomarker studies were performed using surgical specimen tissues and peripheral blood . RESULTS The phase 2 dose was established at 5 daily doses of 5 GyE. Fifty patients were enrolled , of whom 35 patients were treated in the phase 2 portion . There were no grade 4 or 5 toxicities , and only 2 of 35 patients ( 4.1 % ) experienced a grade 3 toxicity event ( chest wall pain grade 1 , colitis grade 1 ) . Of 48 patients eligible for analysis , 37 underwent pancreaticoduodenectomy . Thirty of 37 ( 81 % ) had positive nodes . Locoregional failure occurred in 6 of 37 resected patients ( 16.2 % ) , and distant recurrence occurred in 35 of 48 patients ( 72.9 % ) . With median follow-up of 38 months , the median progression-free survival for the entire group was 10 months , and overall survival was 17 months . Biomarker studies showed significant associations between worse survival outcomes and the KRAS point mutation change from glycine to aspartic acid at position 12 , stromal CXCR7 expression , and circulating biomarkers CEA , CA19 - 9 , and HGF ( all , P<.05 ) . CONCLUSIONS This study met the primary endpoint by showing a rate of 4.1 % grade 3 toxicity for neoadjuvant short-course proton-based chemoradiation . Treatment was associated with favorable local control . In exploratory analyses , KRAS(G12D ) status and high CXCR7 expression and circulating CEA , CA19 - 9 , and HGF levels were associated with poor survival Context . Hadrontherapy is an innovative form of radiotherapy using beams of protons or carbon ions able to destroy some radio-resistant tumours . Because these tumours are highly specific amongst all cancerous tumours , it is impossible to determine the incidence of these diseases from surveillance registries . Goal . To assess , within the Rhône-Alpes region , the incidence of cancers being hadrontherapy indications . Method . Prospect i ve , multicentre continuous data collection during 1 year , by practitioners participating to multidisciplinary tumor board . Tumours are inoperable , radio resistant , at primary stage of development , or locally recurrent , with low metastatic potential . Results . Study involved 27 healthcare centres , 52 groups of specialist practitioners . The estimated  incidence of cancers eligible for hadrontherapy in the Rhône-Alpes region in 2010 , that is , for 34 locations in all , is of 8.5/100 000 inhabitants . Appraisal of the low potential of metastatic progression is impeded , because these are rare diseases , whose outcome is unfamiliar to investigators . Conclusion . Future epidemiological studies will need to focus on prognosis and on the metastatic progression rate of these diseases . Indeed , there are few information available on this subject in the literature that could be used to improve preventive measures , medical care , and the surveillance of these rare cancers PURPOSE This study describes the early clinical outcomes of a prospect i ve phase 2 study of consolidative involved-node proton therapy ( INPT ) as a component of combined-mode therapy in patients with stages I to III Hodgkin lymphoma ( HL ) with mediastinal involvement . METHODS AND MATERIAL S Between September 2009 and June 2013 , 15 patients with newly diagnosed HL received INPT after completing chemotherapy  in an institutional review board-approved protocol comparing the dosimetric impact of PT with those of three-dimensional conformal radiation therapy ( 3DCRT ) and intensity modulated RT . Based on (18)F-Fluorodeoxyglucose positron emission tomography/computed tomography ( (18)F-FDG PET/CT ) response , 5 children received 15 to 25.5 cobalt Gy equivalent ( CGE ) of INPT after receiving 4 cycles of Adriamycin , Bleomycin , Vincristine , Etoposide , Prednisone , Cyclophosphamide or Vincristine , adriamycin , methotrexate , Prednisone chemotherapy , and 10 adults received 30.6 to 39.6 CGE of INPT after 3 to 6 cycles of Adriamycin , Bleomycine , Vinblastine , Dacarbazine . Patients were routinely evaluated for toxicity during and after treatment , using Common Terminology Criteria for Adverse Events , version 3.0 , and for relapse by physical examination and routine imaging . Relapse-free survival ( RFS ) and event-free survival ( EFS ) rates were calculated using the Kaplan-Meier method from the time of diagnosis . RESULTS The median follow-up was 37 months ( range , 26 - 55 ) . Two events occurred during follow-up : 1 relapse ( inside and outside the targeted field ) and 1 transformation into a primary mediastinal large B cell lymphoma . The 3-year RFS rate was 93 % , and the 3-year EFS rate was 87 % . No acute or late grade 3 nonhematologic toxicities were observed . CONCLUSIONS Although decades of follow-up will be needed to realize the likely benefit of PT in reducing the risk of radiation-induced late effects , PT following chemotherapy in patients with HL is well-tolerated , and disease outcomes were similar to those of conventional photon therapy Background and purpose Radiotherapy for recurrent malignant brain tumors is usually limited because of the dose tolerance of the normal brain tissue . The goal of the study was to evaluate the efficacy and feasibility of reirradiation for patients with recurrent malignant brain tumors . Patients and methods The subjects comprised 26 patients with recurrent malignant brain tumors treated with conventional radiotherapy ( RT , n = 8) , stereotactic radiotherapy ( SRT , n = 10 ) , and proton beam therapy ( PBT , n = 8) at our institute . Fifteen patients had glioblastoma , 6 had WHO grade 3 glioma , and 5 had other tumors . The dose of initial radiotherapy was 34.5–94.4 Gy . Different radiation schedules were compared using the equivalent dose in 2-Gy fractions . Results Reirradiation was completed in all patients without a severe acute reaction . The reirradiation doses were 30–60 Gy ( median , 42.3 Gy ) and the total doses for the initial and second treatments were 64.5–150.4 Gy ( median , 100.0 Gy ) . Currently , 11 patients are alive ( median follow-up period , 19.4 months ) and 15 are dead . The median survival and local control periods after reirradiation of the 26 patients were 18.3 and 9.3 months , respectively . For the 15 patients with glioblastoma , these periods were 13.1 and 11.0 months , respectively . Two patients showed radiation necrosis that was treated by surgery or conservative therapy . Conclusion Reirradiation for recurrent malignant brain tumor using conventional RT , SRT , or PBT was feasible and effective in selected cases . Further investigation is needed for treatment optimization for a given patient and tumor condition . ZusammenfassungHintergrund und ZielsetzungBei bösartigen Hirntumoren ist eine operative Beh and lung schwierig und bei rezidivierenden Tumoren schränkt die Dosistoleranz des normalen Hirngewebes eine Strahlentherapie häufig ein . Ziel der Studie war es , die Durchführbarkeit und Wirksamkeit einer erneuten Bestrahlung ( Rebestrahlung ) bei Patienten mit einem rezidivierenden bösartigen intrakraniellen Tumor zu bewerten . Patienten und Method enBei den Prob and en h and elte es sich um 26 Patienten , die mit konventioneller Strahlentherapie  ( RT , n = 8) , stereotaktischer Strahlentherapie ( SRT , n = 10 ) und Protonentherapie ( PBT , n = 8) in unserer Einrichtung beh and elt wurden . Die Beh and lung wurde in Abhängigkeit vom Tumorzust and ausgewählt . Ein Glioblastom hatten 15 Patienten , darunter 6 Patienten mit einem Gliom vom WHO-Grad III . Die Dosis der anfänglichen Strahlentherapie lag bei 34,5–94,4 Gy . Es wurden verschiedene Bestrahlungspläne anh and der Äquivalentdosis in 2-Gy-Fraktionen verglichen . ErgebnisseBei allen Patienten wurde die Rebestrahlung ohne schwere akute Reaktion abgeschlossen . Die Rebestrahlungsdosen betrugen 30–60 Gy ( Median 42,3 Gy ) und die Gesamtdosen der ersten und zweiten Beh and lung 64,5–150,4 Gy ( Median 100,0 Gy ) . Gegenwärtig leben noch 11 Patienten ( medianer Nachuntersuchungszeitraum 19,4 Monate ) , 15 Patienten sind bereits verstorben . Die mediane Überlebenszeit betrug 18,3 Monate und der Zeitraum für die lokale Kontrolle 9,3 Monate bezogen auf alle Patienten sowie 13,1 bzw . 11,0 Monate bezogen auf die Glioblastompatienten . Eine beherrschbare Strahlennekrose hatten 2 der 26 Patienten . SchlussfolgerungenDie Rebestrahlung bei rezidivierendem bösartigem Hirntumor anh and konventioneller RT , SRT oder PBT war durchführbar und wirksam . Weitere Untersuchungen sind notwendig , um die optimale Beh and lung für einzelne Patienten bzw . einen bestimmten Tumorzust and herauszufinden Background While conventionally fractionated radiation therapy alone is an acceptable option for poor prognostic patients with unresectable stage III NSCLC , we hypothesized that accelerated hypofractionated radiotherapy will have similar efficacy without increasing toxicity . Methods This is a retrospective analysis of 300 patients diagnosed with stage III NSCLC treated between 1993 and 2009 . Patients included in the study were medically or surgically inoperable , were free of metastatic disease at initial workup and did not receive concurrent chemotherapy . Patients were categorized into three groups . Group 1 received 45 Gy in 15 fractions over 3 weeks ( Accelerated Radiotherapy ( ACRT ) ) while group 2 received 60 - 63 Gy ( St and ard Radiation Therapy 1 ( STRT1 ) ) and group 3 received > 63 Gy ( St and ard Radiation Therapy ( STRT2 ) ) . Results There were 119 ( 39.7 % ) patients in the ACRT group , 90 ( 30.0 % ) in STRT1 and 91 ( 30.3 % ) in STRT2 . More patients in the ACRT group had KPS ≤ 60 ( p < 0.001 ) , more commonly presented with weight loss > 5 % ( p = 0.002 ) , and had stage 3B disease ( p < 0.001 ) . After adjusting for clinical variables , there were no differences in the radiation groups in terms of the patterns of local or distant tumor control or overall survival . Some benefit in relapse free survival was seen in the STRT1 group as compared to ACRT ( HR = 0.65 , p = 0.011 ) . Acute toxicity profiles in the ACRT were significantly lower for grade ≥ 2 radiation dermatitis ( p = 0.002 ) , nausea/vomiting ( p = 0.022 ) , and weight loss during treatment ( p = 0.020 ) . Conclusions Despite the limitations of a retrospective analysis , our experience of accelerated hypofractionated radiation therapy with 45 Gy in 15 fractions appears to be an acceptable treatment option for poor performance status patients with stage III inoperable tumors . Such a treatment regimen ( or higher doses in 15 fractions ) should be prospect ively evaluated using modern radiation technologies with the addition of sequential high dose chemotherapy in stage III NSCLC PURPOSE Combined-modality treatment is st and ard treatment for patients with clinical stage I/II Hodgkin lymphoma ( HL ) . We hypothesized that an early positron emission tomography ( PET ) scan could be used to adapt treatment . Therefore , we started the r and omized EORTC/LYSA/FIL Intergroup H10 trial evaluating whether involved-node radiotherapy ( IN-RT ) could be omitted without compromising progression-free survival in patients attaining a negative early PET scan after two cycles of ABVD ( doxorubicin , bleomycin , vinblastine , and dacarbazine ) as compared with st and ard combined-modality treatment . PATIENTS AND METHODS Patients age 15 to 70 years with untreated clinical stage I/II HL were eligible . Here we report the clinical outcome of the preplanned interim futility analysis scheduled to occur after documentation of 34 events in the early PET-negative group . Because testing for futility in this noninferiority trial corresponds to testing 
    Output:
    
No phase III trial has been published using proton beam therapy in comparison with the best photon therapy , but numerous retrospective and dosimetric studies have revealed an advantage of proton beam therapy compared to photons , above all in tumours next to parallel organs at risk ( thoracic and abdominal tumours ) .
Use of proton beam therapy is growing for common cancers within clinical trials but some indications could be applied sooner since in silico analysis showed major advantages with this technique