Escalated dose for non-small-cell lung cancer with accelerated hypofractionated three-dimensional conformal radiation therapy. Dosimetric Feasibility of Dose Escalation Using SBRT Boost for Stage III Non-Small Cell Lung Cancer Accelerated high-dose radiotherapy alone or combined with either concomitant or sequential chemotherapy; treatments of choice in patients with Non-Small Cell Lung Cancer Image guided hypofractionated 3-dimensional radiation therapy in patients with inoperable advanced stage non-small cell lung cancer. Toxicity and outcome results of a class solution with moderately hypofractionated radiotherapy in inoperable Stage III non-small cell lung cancer using helical tomotherapy. Concurrent chemoradiotherapy with tomotherapy in locally advanced non-small cell lung cancer: a phase i, docetaxel dose-escalation study, with hypofractionated radiation regimen Accelerated hypo-fractionated radiotherapy for non small cell lung cancer: results from 4 UK centres. Accelerated hypofractionated radiation therapy compared to conventionally fractionated radiation therapy for the treatment of inoperable non-small cell lung cancer Randomised trial of sequential versus concurrent chemo-radiotherapy in patients with inoperable non-small cell lung cancer (EORTC 08972-22973). Results of a phase I study to dose escalate using intensity modulated radiotherapy guided by combined PET/CT imaging with induction chemotherapy for patients with non-small cell lung cancer. Dose-limiting toxicity after hypofractionated dose-escalated radiotherapy in non-small-cell lung cancer. Concomitant boost radiation therapy for inoperable non-small-cell lung cancer: preliminary report of a prospective randomized study. Dose escalation of accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine and carboplatin chemotherapy in unresectable stage III non-small-cell lung cancer: a phase I trial Pilot study of accelerated radiotherapy with concurrent chemotherapy for stage III non-small cell lung cancer. Higher biologically effective dose of radiotherapy is associated with improved outcomes for locally advanced non-small cell lung carcinoma treated with chemoradiation: an analysis of the Radiation Therapy Oncology Group. A prospective randomized study of various irradiation doses and fractionation schedules in the treatment of inoperable non‐oat‐cell carcinoma of the lung. Preliminary report by the radiation therapy oncology group Randomized phase II study of concurrent cisplatin/etoposide or paclitaxel/carboplatin and thoracic radiotherapy in patients with stage III non-small cell lung cancer. Toxicity report of a phase 1/2 dose‐escalation study in patients with inoperable, locally advanced nonsmall cell lung cancer with helical tomotherapy and concurrent chemotherapy Stereotactic body radiation therapy can be used safely to boost residual disease in locally advanced non-small cell lung cancer: a prospective study. A phase II trial of accelerated hypofractionated three-dimensional conformal radiation therapy in locally advanced non-small cell lung cancer. Phase I/II study of treatment of locally advanced (T3/T4) non-oat cell lung cancer with concomitant boost radiotherapy by the Radiation Therapy Oncology Group (RTOG 83-12): long-term results. Stereotactic body radiation therapy for inoperable early stage lung cancer. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. Primary analysis of the phase II component of a phase I/II dose intensification study using three-dimensional conformal radiation therapy and concurrent chemotherapy for patients with inoperable non-small-cell lung cancer: RTOG 0117. ARCON: accelerated radiotherapy with carbogen and nicotinamide in non small cell lung cancer: a phase I/II study by the EORTC. Hypofractionated/accelerated radiotherapy with cytoprotection (HypoARC) combined with vinorelbine and liposomal doxorubicin for locally advanced non-small cell lung cancer (NSCLC). Long-Term Results of a Phase II Trial of Induction Paclitaxel-Carboplatin Followed by Concurrent Radiation Therapy and Weekly Paclitaxel and Consolidation Paclitaxel-Carboplatin in Stage III Non-small Cell Lung Cancer Phase 1 study of dose escalation in hypofractionated proton beam therapy for non-small cell lung cancer. Final results of the randomized phase III CHARTWEL-trial (ARO 97-1) comparing hyperfractionated-accelerated versus conventionally fractionated radiotherapy in non-small cell lung cancer (NSCLC). Additional weekly Cetuximab to concurrent chemoradiotherapy in locally advanced non-small cell lung carcinoma: efficacy and safety outcomes of a randomized, multi-center phase II study investigating.
BACKGROUND AND PURPOSE To prospect ively assess the feasibility and efficacy of a hypofractionated accelerated radiotherapy regimen ( 72 Gy in 24 daily fractions , 3 Gy per fraction ) in patients ( pts ) with non-resectable non-small-cell lung cancer ( NSCLC ) . MATERIAL AND METHODS We included 25 pts with a histologically or cytologically proven NSCLC , with KPS > or = 70 and < or = 10 % weight loss over prior three months , and with tumour stage I/II medically inoperable ( 9 pts ) or non-resectable stage III a/b without pleural effusion ( 16 pts ) . Eleven pts received induction chemotherapy . No more than 30 % of the combined lung volume could receive more than 25 Gy and the maximal biological effective dose to the spinal cord was maintained below 44 Gy . RESULTS No grade -4 acute toxicity event was reported . Two pts had a treatment break because of grade -3 acute oesophagitis . Twenty-two pts were evaluable for long-term toxicity ( median follow-up=9.7 months , range 4 to 30.2 months ) . There were 4 Grade -1 pulmonary and 2 Grade -1 oesophageal long-term toxicity events . Twenty-two pts were evaluable for tumour response with 7 complete and 8 partial responses , 5 stable diseases and 2 progressive diseases . The actuarial 1-year overall and thoracic-progression-free survival rates were 68 % and 72 % respectively . CONCLUSIONS This study demonstrates the feasibility of the experimental radiotherapy schedule , however more data are needed to confirm its efficacy Purpose : St and ard chemoradiation therapy for stage III non-small cell lung cancer ( NSCLCa ) results in suboptimal outcomes with a high rate of local failure and poor overall survival . We hypothesize that dose escalation using stereotactic body radiotherapy ( SBRT ) boost could improve upon these results . We present here a study evaluating the dosimetric feasibility of such an approach . Methods : Anonymized CT data sets from five r and omly selected patients with stage III NSCLCa undergoing definitive chemoradiation therapy in our department with disease volumes appropriate for SBRT boost were selected .  Three-dimensional conformal radiation therapy ( 3D-CRT ) plans to 50.4 Gy in 28 fractions were generated follow by SBRT plans to two dose levels , 16 Gy in two fractions and 28 Gy in two fractions . SBRT plans and total composite ( 3D-CRT and SBRT ) were optimized and evaluated for target coverage and dose to critical structures ; lung , esophagus , cord , and heart . Results : All five plans met predetermined target coverage and normal tissue dose constraints . PTV V95 was equal to or greater than 95 % in all cases . The cumulative lung V20 and V5 of the combined 3D-CRT and SBRT plans were less than or equal to 30 and 55 % , respectively . The 5 cc esophageal dose was less than 12 Gy for all low and high dose SBRT plans . The cumulative dose to the esophagus was also acceptable with less than 10 % of the esophagus receiving doses in excess of 50 Gy . The cumulative spinal cord dose was less than 33 Gy and heart V25 was less than 5 % . Conclusion : The combination of chemoradiation to 50.4 Gy followed by SBRT boost to gross disease at the primary tumor and involved regional lymph nodes is feasible with respect to normal tissue dose constraints in this dosimetric pilot study . A phase I/II trial to evaluate the clinical safety and efficacy of this approach is being undertaken Background Results of high-dose chemo-radiotherapy ( CRT ) , using the treatment schedules of EORTC study 08972/22973 or radiotherapy ( RT ) alone were analyzed among all patients ( pts ) with Non Small Cell Lung Cancer ( NSCLC ) treated with curative intent in our department from 1995–2004 . Material Included are 131 pts with medically inoperable or with irresectable NSCLC ( TNM stage I:15 pts , IIB:15 pts , IIIA:57 pts , IIIB:43 pts , X:1 pt).TreatmentGroup I : Concomitant CRT : 66 Gy/2.75 Gy/24 fractions (fx)/33 days combined with daily administration of cisplatin 6 mg/m2 : 56 pts ( st and ard).Group II : Sequential CRT : two courses of a 21-day schedule of chemotherapy ( gemcitabin 1250 mg/m2 d1 , cisplatin 75 mg/m2 d2 ) followed by 66 Gy/2.75 Gy/24 fx/33 days without daily cisplatin : 26 pts . Group III : RT : 66 Gy/2.75 Gy/24 fx/33 days or 60 Gy/3 Gy/20 fx/26 days : 49 pts . Results The 1 , 2 , and 5 year actuarial overall survival ( OS ) were 46 % , 24 % , and 15 % , respectively . At multivariate analysis the only factor with a significantly positive influence on OS was treatment with  chemo-radiation  ( P = 0.024 ) ( 1- , 2- , and 5-yr OS 56 % , 30 % and 22 % respectively ) . The incidence of local recurrence was 36 % , the incidence of distant metastases 46%.Late complications grade 3 were seen in 21 pts and grade 4 in 4 patients . One patient had a lethal complication ( oesophageal ) . For 32 patients insufficient data were available to assess late complications . Conclusion In this study we were able to reproduce the results of EORTC trial 08972/22973 in a non-selected patient population outside of the setting of a r and omised trial . Radiotherapy ( 66 Gy/24 fx/33 days ) combined with either concomitant daily low dose cisplatin or with two neo-adjuvant courses of gemcitabin and cisplatin are effective treatments for patients with locally advanced Non-Small Cell Lung Cancer . The concomitant schedule is also suitable for elderly people with co-morbidity PURPOSE Hypofractionated radiation therapy ( HypoRT ) can potentially improve local control with a higher biological effect and shorter overall treatment time . Response , local control , toxicity rates , and survival rates were evaluated in patients affected by inoperable advanced stage non-small cell lung cancer ( NSCLC ) who received HypoRT .  METHODS AND MATERIAL S Thirty patients with advanced NSCLC were enrolled ; 27 % had stage IIIA , 50 % had stage IIIB , and 23 % had stage IV disease . All patients underwent HypoRT with a prescribed total dose of 60 Gy in 20 fractions of 3 Gy each . Radiation treatment was delivered using an image guided radiation therapy technique to verify correct position . Toxicities were grade d according to Radiation Therapy Oncology Group morbidity score . Survival rates were estimated using the Kaplan-Meier method . RESULTS The median follow-up was 13 months ( range , 4 - 56 months ) . All patients completed radiation therapy and received the total dose of 60 Gy to the primary tumor and positive lymph nodes . The overall response rate after radiation therapy was 83 % ( 3 patients with complete response and 22 patients with partial response ) . The 2-year overall survival and progression-free survival rates were 38.1 % and 36 % , respectively . Locoregional recurrence/persistence occurred in 11 ( 37 % ) patients . Distant metastasis occurred in 17 ( 57 % ) patients . Acute toxicities occurred consisting of grade 1 to 2 hematological toxicity in 5 patients ( 17 % ) and grade 3 in 1 patient ; grade 1 to 2 esophagitis in 12 patients ( 40 % ) and grade 3 in 1 patient ; and grade 1 to 2 pneumonitis in 6 patients ( 20 % ) and grade 3 in 2 patients ( 7 % ) . Thirty-three percent of patients developed grade 1 to 2 late toxicities . Only 3 patients developed grade 3 late adverse effects : esophagitis in 1 patient and pneumonitis in 2 patients . CONCLUSIONS Hypofractionated curative radiation therapy is a feasible and well-tolerated treatment for patients with locally advanced NSCLC . R and omized studies are needed to compare HypoRT to conventional treatment PURPOSE To prospect ively assess the feasibility , toxicity , and local control of a class solution protocol of moderately hypofractionated tomotherapy in Stage III , inoperable , locally advanced non-small-cell lung cancer patients . METHODS AND MATERIAL S Eligible patients were treated according to a uniform class solution ( 70.5 Gy in 30 fractions ) with fixed constraints and priorities using helical tomotherapy . Toxicity monitoring was performed using the Radiation Therapy Oncology Group criteria and the National Cancer Institute Common Terminology Criteria and Adverse Events ( CTCAE ) version 3.0 . Pulmonary function tests were performed at the start and repeated at 3 months after treatment . RESULTS Our class solution result ed in a deliverable plan in all 40 consecutive patients .  Acute Grade 3 lung toxicity was seen in 10 % of patients . Two patients died during acute follow-up with pulmonary toxicity . Correlations were found between changes in pulmonary function test results and mean lung dose or the lung volume receiving 20 Gy ( V(20 ) ) . The correlation was strongest for lung diffusion capacity for carbon monoxide . A V(20 ) of > 27 % and > 32 % were predictive for Grade s 2 and 3 acute lung toxicity respectively ( p < 0.05 ) . Late Grade 3 toxicity was exclusively pulmonary , with an incidence of 16 % . Overall Grade 3 lung toxicity correlated with a mean lung dose of > 18 Gy and a median lung dose of > 5 Gy ( p < 0.05 ) . Median survival was 17 months , and the 1-year and 2-year local progression-free survivals were 66 % and 50 % , respectively . CONCLUSION The current class solution using moderately hypofractionated helical tomotherapy in patients with locally advanced non-small-cell lung cancer is feasible . Toxicity was acceptable and in line with other reports on intensity-modulated radiotherapy . The local progression-free survival was encouraging considering the unselected population Background Concurrent chemo-radiotherapy is demonstrately superior to sequential chemo-radiotherapy in the treatment of advanced Non-Small-Cell Lung Cancer not suitable for surgery .  Docetaxel is considered to enhance the cytotoxic effect of radiotherapy on the tumour cells . Tomotherapy ( HT ) is a novel radiotherapeutic technique , which allows the delivery of Image Guided-IMRT ( IG-IMRT ) , with a highly conformal radiation dose distribution . The goal of the study was to estimate tolerability of Docetaxel concurrent with IMRT and to find the maximum tolerated dose of weekly Docetaxel concurrent with IMRT delivered with HT Tomotherapy after induction chemotherapy with Cisplatin and Docetaxel in patients affected with stage III Non-Small Cell Lung Cancer . Methods We design ed a phase I , dose-finding study to determine the dose of weekly Docetaxel concurrent with Tomotherapy after induction chemotherapy , in patients affected by Non-Small Cell Lung Cancer with Stage III disease , not suitable for surgery . Results Concurrent weekly Docetaxel and Tomotherapy are feasible ; we did not reach a maximum tolerated dose , because no life-threatening toxicity was observed , stopping the accrual at a level of weekly docetaxel 38 mg/m2 , a greater dose than in previous assessment s , from both phase-I studies with weekly docetaxel alone and with Docetaxel concomitant with st and ard radiotherapy . Conclusions Concurrent weekly Docetaxel and Tomotherapy are feasible , and even with Docetaxel at 38 mg/m2/week we did not observe any limiting toxicity . For those patients who completed the combined chemo-radio treatment , median progression-free survival ( PFS ) was 20 months and median overall survival ( OS ) was 24 months BACKGROUND AND PURPOSE A variety of radiotherapy fractionations are used as potentially curative treatments for non-small cell lung cancer . In the UK , 55 Gy in 20 fractions over 4 weeks ( 55/20 ) is the most commonly used fractionation schedule , though it has not been vali date d in r and omized phase III trials . This audit pooled together existing data from 4 UK centres to produce the largest published series for this schedule . MATERIAL S AND METHODS 4 UK centres contributed data ( Cambridge , Cardiff , Glasgow and Sheffield ) . Case notes and radiotherapy records of radically treated patients between 1999 and 2007 were retrospectively review ed . Basic patient demographics , tumour characteristics , radiotherapy and survival data were collected and analysed . RESULTS 609 patients were identified of whom 98 % received the prescribed dose of 55/20 . The median age was 71.3 years , 62 % were male . 90 % had histologically confirmed NSCLC , 49 % had stage I disease . 27 % had received chemotherapy  ( concurrent or sequential ) with their radiotherapy . The median overall survival from time of diagnosis was 24.0 months and 2 year overall survival was 50 % . CONCLUSION These data show respectable results for patients treated with accelerated hypo-fractionated radiotherapy for NSCLC with outcomes comparable to those reported for similar schedules and represent the largest published series to date for 55/20 regime 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 UNLABELLED A r and omised phase III study was performed comparing sequential ( S ) and concurrent ( C ) chemo-radiotherapy ( CRT ) in non-small cell lung cancer ( NSCLC ) patients . METHODS One hundred and fifty-eight patients were r and omised to receive two courses of Gemcitabine ( 1250mg/m(2 ) days 1 , 8) and Cisplatin ( 75mg/m(2 ) day 2 ) prior to , or daily low-dose Cisplatin ( 6mg/m(2 ) ) concurrent with radiotherapy , consisting of 24 fractions of 2.75Gy in 32 days , with a total dose of 66Gy . RESULTS Acute haematological toxicity grade 3/4 was more pronounced in the sequential ( S ) ( 30 % versus 6 % ) , oesophagitis grade 3/4 more frequent in the concurrent ( C ) arm ( 5 % versus 14 % ) . Late oesophagitis grade 3 was 4 % ( S and C ) , pneumonitis grade 3/4 14 % ( S ) and 18 % ( C ) . Because of the poor power of the study no significant differences in median survival ( MS ) , overall survival ( OS ) and progression-free survival ( PFS ) could be detected . MS was 16.2 ( S ) and 16.5 ( C ) months , 2-year OS was 34 % ( S ) and 39 % ( C ) , 3-year OS was 22 % ( S ) and 34 % ( C ) . CONCLUSION Radiotherapy 66Gy given concurrently with daily low-dose Cisplatin or after two courses of Gemcitabine/Cisplatin was well tolerated . Due to early closure no conclusions can be reached on the relative merits ; both arms showed good OS Intensity modulated radiation therapy ( IMRT ) guided by PET/CT imaging with respiratory gating was employed to dose escalate in patients with non-small cell lung cancer ( NSCLC ) , using accelerated fractionation with induction chemotherapies . One patient developed a grade 5 pneumonitis and the study was halted at 84 Gy in 35 fractions PURPOSE Local failure rates after radiation therapy ( RT ) for locally advanced non-small-cell lung cancer ( NSCLC ) remain high . Consequently , RT dose intensification strategies continue to be explored , including hypofractionation , which allows for RT acceleration that could potentially improve outcomes . The maximum-tolerated dose ( MTD ) with dose-escalated hypofractionation has not been adequately defined . PATIENTS AND METHODS Seventy-nine patients with NSCLC were enrolled on a prospect i ve single-institution phase I trial of dose-escalated hypofractionated RT without concurrent chemotherapy . Escalation of dose per fraction was performed according to patients ' stratified risk for radiation pneumonitis with total RT doses ranging from 57 to 85.5 Gy in 25 daily fractions over 5 weeks using intensity-modulated radiotherapy . The MTD was defined as the maximum dose with ≤ 20 % risk of severe toxicity . RESULTS No grade 3 pneumonitis was observed and an MTD for acute toxicity was not identified during patient accrual . However , with a longer follow-up period , grade 4 to 5 toxicity occurred in six patients and was correlated with total dose ( P = .004 ) . An MTD was identified at 63.25 Gy in 25 fractions . Late grade 4 to 5 toxicities were attributable to damage to central and perihilar structures and correlated with dose to the proximal bronchial tree . CONCLUSION Although this dose-escalation model limited the rates of clinical ly significant pneumonitis , dose-limiting toxicity occurred and was dominated by late radiation toxicity involving central and perihilar structures . The identified dose-response for damage to the proximal bronchial tree warrants caution in future dose-intensification protocol s , especially when using hypofractionation PURPOSE The radiation therapy results for patients with inoperable non-small-cell lung cancer ( NSCLC ) have been disappointing . Tumor dose escalation using concomitant boost technique ( CBT ) has been shown to improve local control in a few prospect i ve studies . This trial was carried out to prospect ively assess the radiation response and acute toxicity of CBT in comparison to the conventional treatment technique ( CTT ) . METHODS AND MATERIAL S Ninety-seven consecutive eligible patients were entered in this prospect i ve clinical trial between November 1994 and February 1998 . Patients were r and omized to receive either CBT ( 43 patients ) or CTT ( 54 patients ) radiation therapy .  These patients either refused chemotherapy or were judged as unsuitable for chemotherapy . Patients in the CBT group received 46.8 Gy in 26 fractions using large fields that encompassed the gross and occult disease . A concomitant boost of 18.2 Gy ( 0.7 Gy per fraction ) was delivered to the gross disease using small fields with 1.5-cm margins . The small fields were treated concurrently with the large fields and the total dose to the tumor area was 65 Gy in 26 fractions . Patients in the CTT group received 70.8 Gy in 38 fractions . The acute toxicity between each group was compared . The response rate was analyzed and compared by treatment group , gender , age , stage , histology , initial Karnofsky performance score ( KPS ) , severity of acute toxicity , and maximum body weight loss ( MBWL ) during treatment course . RESULTS The demographic parameters such as sex , age , and stage were evenly distributed in each treatment group . The majority of these patients had Stage IIIA and IIIB disease . Overall median treatment times were 39 days for the CBT group of patients and 62 days for the CTT group . No treatment-related mortality was found . There were 2 patients in the CTT group with acute RTOG Grade 3 lung toxicity , and no Grade 3 lung or esophageal toxicity was observed in CBT group . The response rates , assessed by radiographic images , were 69.8 % and 48.1 % for the CBT and CTT patients , respectively . Univariate and multivariate analysis revealed that patients in the CBT group , patients with better KPS , and patients with more severe acute toxicity had a higher response rate . CONCLUSION This study demonstrates that concomitant boost radiation therapy is tolerable , and produces a superior response rate than conventional radiation therapy for patients with inoperable NSCLC . The length of treatment was reduced from 38 to 26 treatment days , almost a 30 % reduction Background Accelerated hypofractionated radiotherapy can shorten total treatment time and overcome the accelerated re population of tumour cells during radiotherapy . This therapeutic approach has demonstrated good efficacy in the treatment of locally advanced non-small-cell lung cancer ( NSCLC ) . However , the optimal fractionation scheme remains uncertain . The purpose of this phase I trial was to explore the maximum tolerated dose ( MTD ) of accelerated hypofractionated three-dimensional conformal radiotherapy ( 3-DCRT ) ( at 3 Gy/fraction ) administered in combination with concurrent vinorelbine ( NVB ) and carboplatin ( CBP ) chemotherapy for unresectable stage III NSCLC . Methods Previously untreated cases of unresectable stage III NSCLC received accelerated hypofractionated 3-DCRT , delivered at 3 Gy per fraction , once daily , with five fractions per week . The starting dose was 66 Gy and an increment of 3 Gy was utilized . Higher doses continued to be tested in patient groups until the emergence of dose-limiting toxicity ( DLT ) . The MTD was regarded as the dose that was one step below the dose at which DLT occurred . Patients received at least one cycle of a concurrent two-drug chemotherapy regimen of NVB and CBP . Results A total of 13 patients were enrolled and progressed through three dose escalation groups : 66 Gy , 69 Gy , and 72 Gy . No treatment-related deaths occurred . The major adverse events included radiation oesophagitis , radiation pneumonitis , and neutropenia . Nausea , fatigue , and anorexia were commonly observed , although the magnitude of these events was typically relatively minor . Among the entire group , four instances of DLT were observed , including two cases of grade 3 radiation oesophagitis , one case of grade 3 radiation pneumonitis , and one case of grade 4 neutropenia . All of these cases of DLT occurred in the 72 Gy group . Therefore , 72 Gy was design ated as the DLT dose level , and the lower dose of 69 Gy was regarded as the MTD . Conclusions For unresectable stage III NSCLC 69 Gy ( at 3 Gy/fraction ) was the MTD of accelerated hypofractionated 3-DCRT administered in combination with concurrent NVB and CBP chemotherapy . The toxicity of this chemoradiotherapy regimen could be tolerated . A phase II trial is recommended to further evaluate the efficacy and safety of this regimen The purpose of this pilot study was to determine the safety and feasibility of accelerated fractionation ( via concomitant boost ) radiotherapy ( XRT ) with concurrent carboplatin/paclitaxel chemotherapy for locally advanced stage III non-small cell lung carcinoma .  Radiotherapy consisted of 3-dimensional conformal techniques to 60 Gy continuous course , over 4 weeks , via 3-dimensional conformal techniques . Once-daily treatments were used ; the large field ( including gross tumor and selected regional nodes ) was given a daily dose of 2.2 Gy ( to 44 Gy ) , with a 0.8 Gy concomitant boost ( field within a field ) for an additional 16 Gy to the gross tumor volume . Weekly carboplatin at an area under the curve ( AUC ) of 2 plus paclitaxel 50 mg/m2 were given during XRT , followed by two cycles of systemic-dose carboplatin AUC 6 , every 4 weeks plus paclitaxel 100 mg/m2 , 3 weeks out of 4 , were planned . The nutritional supplement glutamine 10 mg 3 times per day was prescribed in an effort to decrease esophagitis . Before the early closure of this study , five patients were enrolled , of whom four were evaluable for toxicity/feasibility . No patient experienced grade 3 + acute nonhematologic toxicity during concurrent chemoradiotherapy .  Hematologic toxicity was significant in the post-XRT consolidation phase , result ing in dose reduction and /or discontinuation in three of four patients . More notably , two patients experienced serious nonhematologic late toxicity . One patient developed a grade 4 tracheoesophageal fistula that probably contributed to her death 6 months after treatment , and one patient developed grade 3 pulmonary complications including severe oxygen-dependent radiation pneumonopathy . Three patients are alive without disease progression at 14 , 20 , and 21 months follow-up . Despite the use of 3-dimensional conformal technology , this regimen of concomitant boost accelerated hypofractionated XRT with concurrent and systemic chemotherapy was excessively toxic and not feasible . Extreme caution must be exercised in design ing studies of XRT dose intensification with concurrent chemotherapy PURPOSE Patients treated with chemoradiotherapy for locally advanced non-small-cell lung carcinoma ( LA-NSCLC ) were analyzed for local-regional failure ( LRF ) and overall survival ( OS ) with respect to radiotherapy dose intensity . METHODS AND MATERIAL S This study combined data from seven Radiation Therapy Oncology Group ( RTOG ) trials in which chemoradiotherapy was used for LA-NSCLC : RTOG 88 - 08 (  chemoradiation arm only ) , 90 - 15 , 91 - 06 , 92 - 04 , 93 - 09 (  nonoperative  arm only ) , 94 - 10 , and 98 - 01 . The radiotherapeutic  biologically effective dose ( BED ) received by each individual patient was calculated , as was the overall treatment time-adjusted BED ( tBED ) using st and ard formulae . Heterogeneity testing was done with chi-squared statistics , and weighted pooled hazard ratio estimates were used . Cox and Fine and Gray 's proportional hazard models were used for OS and LRF , respectively , to test the associations between BED and tBED adjusted for other covariates . RESULTS A total of 1,356 patients were analyzed for BED ( 1,348 for tBED ) . The 2-year and 5-year OS rates were 38 % and 15 % , respectively . The 2-year and 5-year LRF rates were 46 % and 52 % , respectively . The BED ( and tBED ) were highly significantly associated with both OS and LRF , with or without adjustment for other covariates on multivariate analysis ( p < 0.0001 ) . A 1-Gy BED increase in radiotherapy dose intensity was statistically significantly associated with approximately 4 % relative improvement in survival ; this is another way of expressing the finding that the pool-adjusted hazard ratio for survival as a function of BED was 0.96 . Similarly , a 1-Gy tBED increase in radiotherapy dose intensity was statistically significantly associated with approximately 3 % relative improvement in local-regional control ; this is another way of expressing the finding that the pool-adjusted hazard ratio as a function of tBED was 0.97 . CONCLUSIONS Higher radiotherapy dose intensity is associated with improved local-regional control and survival in the setting of chemoradiotherapy Preliminary analysis is presented of a prospect i ve r and omized study involving 365 patients with histologically proven unresectable non‐oat‐cell carcinoma of the lung treated with definitive radiotherapy .  The patients were r and omized to one of four treatment regimens : 4000 rad split course ( 2000 rad in five fractions one week , two weeks rest , and an additional 2000 rad in five fractions in one week ) or 4000 , 5000 , or 6000‐rad continuous courses in five fractions per week . Ninety to 100 patients were accessioned to each group . The one‐year survival rate is 50 % and the two‐year survival rate , 25 % . The patients treated with the split course have the lowest survival rate ( 10 % at two years ) in comparison with the other groups ( range = 20–25 % ) . The complete and partial local regression of tumor was 49 % in patients treated with 4000 rad and 55 % in the groups treated with 5000 and 6000 rad . For patients who achieved complete regression of the tumor following irradiation , the two‐year survival rate is 40 % , in contrast to 20 % for those with partial regression , and no survivors among the patients with stable or progressive disease . The incidence of intrathoracic recurrence was 33 % for patients treated with 6000 rad , 39 % for those receiving 5000 rad , and 44–49 % for those treated with a 4000‐rad split or continuous course . At present , the data strongly suggest that patients treated with 5000 or 6000 rad have a better response , tumor control , and survival rate than those receiving lower doses . However , additional followup of patients at risk in each group will be necessary before a final conclusion is drawn . Patients with high performance status ( Kornofsky index higher than 70 ) , or with tumors in earlier stages ( T1N2 or T3N0 ) have a two‐year survival rate of approximately 40 % , in comparison with 20 % for other patients . The various irradiation regimens have been well tolerated , with complications being slightly higher in the 4000‐rad split course group ( 10 severe and 2 life‐threatening ) and in the 6000‐rad continuous course group ( 9 severe and 4 life‐threatening ) . The most frequent complications have been pneumonitis , pulmonary fibrosis , and dysphagia due to transient esophagitis . Further investigation will be necessary before the optimal management of patients with bronchogenic carcinoma by irradiation is established OBJECTIVE To evaluate the activity and safety of concurrent thoracic radiotherapy ( TRT ) plus weekly paclitaxel/carboplatin ( PC ) regimen compared with widely used cisplatin/etoposide ( PE ) regimen in patients with unresectable stage III non-small cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients were r and omly assigned to receive the following treatments : PE arm , cisplatin ( 50mg/m(2 ) ) on days 1 , 8 , 29 , and 36 and etoposide ( 50 mg/m(2 ) ) on days 1 - 5 and 29 - 33 plus 60 Gy of TRT ; PC arm , weekly concurrent carboplatin ( AUC = 2 ) and paclitaxel ( 45 mg/m(2 ) ) plus 60 Gy of TRT . RESULTS A total of 65 patients were r and omized ( PE arm , n = 33 ; PC arm , n = 32 ) . The 3-year overall survival ( OS ) was significantly better in the PE arm than in the PC arm ( 33.1 % vs. 13 % , P = .04 ) . The incidence of Grade 3/4 neutropenia was 78.1 % in the PE arm and 51.5 % in the PC arm ( P = .05 ) . The rate of Grade 2 or greater radiation pneumonitis was 25 % in the PE arm and 48.5 % in the PC arm ( P = .09 ) . CONCLUSIONS Compared to PE regimen , weekly PC regimen can not be recommended since it failed to achieve an improvement in either OS or PFS The objective of the current study was to evaluate the feasibility and toxicity of radiation dose escalation with concurrent chemotherapy using helical tomotherapy ( HT ) in patients with inoperable , locally advanced , stage III nonsmall cell lung cancer ( LANSCLC ) ( grading determined according to the American Joint Committee on Cancer 6th edition grading system ) PURPOSE To report the results of a prospect i ve , single-institution study evaluating the feasibility of conventional chemoradiation ( CRT ) followed by stereotactic body radiation therapy ( SBRT ) as a means of dose escalation for patients with stage II-III non-small cell lung cancer ( NSCLC ) with residual disease . METHODS AND MATERIAL S Patients without metastatic disease and with radiologic evidence of limited residual disease ( ≤5 cm ) within the site of the primary tumor and good or complete nodal responses after st and ard CRT to a target dose of 60 Gy were considered eligible . The SBRT boost was done to achieve a total combined dose biological equivalent dose > 100 Gy to the residual primary tumor , consisting of 10 Gy × 2 fractions ( 20 Gy total ) for peripheral tumors , and 6.5 Gy × 3 fractions ( 19.5 Gy total ) for medial tumors using the Radiation Therapy Oncology Group protocol 0813 definitions . The primary endpoint was the development of grade ≥3 radiation pneumonitis ( RP ) . RESULTS After a median follow-up of 13 months , 4 patients developed acute grade 3 RP , and 1 ( 2.9 % ) developed late and persistent grade 3 RP . No patients developed grade 4 or 5 RP . Mean lung dose , V2.5 , V5 , V10 , and V20 values were calculated for the SBRT boost , and none were found to significantly predict for RP . Only advancing age ( P=.0147 ) , previous smoking status ( P=.0505 ) , and high CRT mean lung dose ( P=.0295 ) were significantly associated with RP development . At the time of analysis , the actuarial local control rate at the primary tumor site was 82.9 % , with only 6 patients demonstrating recurrence . CONCLUSIONS Linear accelerator-based SBRT for dose escalation of limited residual NSCLC after definitive CRT was feasible and did not increase the risk for toxicity above that for st and ard radiation therapy PURPOSE The aim of this study is to evaluate the safety and efficacy of accelerated hypofractionated radiotherapy ( HypoRT ) combined with sequential chemotherapy in locally advanced non-small cell lung cancer ( NSCLC ) . MATERIAL S AND METHODS A total of 34 patients with stage III NSCLC were enrolled . All patients received accelerated HypoRT ( initially 50Gy/20 fractions , then a fraction dose of 3Gy ) using three-dimensional conformal radiation therapy ( 3D-CRT ) , omitting elective nodal irradiation ( ENI ) , to a total dose of 65 - 68Gy . All patients received two cycles of induction chemotherapy ; 1 - 2 cycles of consolidation chemotherapy were given to 31 patients . The primary outcome measure was a profile of radiation toxicity . The secondary endpoints included overall survival ( OS ) , progression-free survival ( PFS ) , locoregional PFS ( LR-PFS ) and the pattern of initial failure . RESULTS Radiation toxicity was minimal . The median and 3-year OS , PFS were 19.0 months , 32.1 % ; 10.0 months , 29.8 % , respectively . The 1- , 2- , and 3-year LR-PFS were 69.6 % , 60.9 % and 60.9 % , respectively . No patient experienced isolated elective nodal failure as the first site of failure . CONCLUSION This study suggests that accelerated HypoRT using 3D-CRT omitting ENI can be used in combination with sequential chemotherapy in locally advanced NSCLC PURPOSE This pilot study was undertaken to evaluate the effect of high dose-per-fraction radiotherapy given to the tumor primary concurrently with conventional fractionated radiotherapy to the electively irradiated regional lymph nodes ( concomitant boost ) . This article reports the late results of toxicity and survival . METHODS AND MATERIAL S Fifty-nine patients with histologically proven clinical Stage T3-T4 , N1 - 3 nonsmall cell lung cancer were prospect ively enrolled in this study . Fifty-six were evaluable for late effects . The treatment delivered 2.68 Gy daily to the primary tumor , 5 days a week , to a total dose of 75 Gy in 28 fractions in 5.5 weeks . At the same treatment sessions , the electively irradiated nodal areas received 1.8 Gy daily , 5 days per week , to a total dose of 50.4 Gy . All doses were calculated with heterogeneity corrections for lung density . RESULTS Presently , one patient remains alive at 7.7 years . Median survival was 10.0 months with 1- , 2- , 3- , and 5-year survival rates of 41 % , 25 % , 18 % , and 4 % , respectively . Three patients developed severe late complications , including pulmonary fibrosis and osteonecrosis . The remainder of the patients , however , developed only grade 1 or 2 pulmonary fibrosis and /or pneumonitis . CONCLUSION We conclude that concomitant boost radiotherapy in the manner reported result ed in acceptable late toxicity . The 2- and 3-year survivals compared favorably with the best-reported results in the literature with either hyperfractionated or chemoradiotherapy treatment . Studies that deliver higher radiotherapy doses to the gross tumor combined with chemotherapy are in order CONTEXT Patients with early stage but medically inoperable lung cancer have a poor rate of primary tumor control ( 30%-40 % ) and a high rate of mortality ( 3-year survival , 20%-35 % ) with current management . OBJECTIVE To evaluate the toxicity and efficacy of stereotactic body radiation therapy in a high-risk population of patients with early stage but medically inoperable lung cancer . DESIGN , SETTING , AND PATIENTS Phase 2 North American multicenter study of patients aged 18 years or older with biopsy-proven peripheral T1-T2N0M0 non-small cell tumors ( measuring < 5 cm in diameter ) and medical conditions precluding surgical treatment . The prescription dose was 18 Gy per fraction x 3 fractions ( 54 Gy total ) with entire treatment lasting between 1(1/2 ) and 2 weeks . The study opened May 26 , 2004 , and closed October 13 , 2006 ; data were analyzed through August 31 , 2009 . MAIN OUTCOME MEASURES The primary end point was 2-year actuarial primary tumor control ; secondary end points were disease-free survival ( ie , primary tumor , involved lobe , regional , and disseminated recurrence ) , treatment-related toxicity , and overall survival . RESULTS A total of 59 patients accrued , of which 55 were evaluable ( 44 patients with T1 tumors and 11 patients with T2 tumors ) with a median follow-up of 34.4 months ( range , 4.8 - 49.9 months ) . Only 1 patient had a primary tumor failure ; the estimated 3-year primary tumor control rate was 97.6 % ( 95 % confidence interval [ CI ] , 84.3%-99.7 % ) . Three patients had recurrence within the involved lobe ; the 3-year primary tumor and involved lobe ( local ) control rate was 90.6 % ( 95 % CI , 76.0%-96.5 % ) . Two patients experienced regional failure ; the local-regional control rate was 87.2 % ( 95 % CI , 71.0%-94.7 % ) . Eleven patients experienced disseminated recurrence ; the 3-year rate of disseminated failure was 22.1 % ( 95 % CI , 12.3%-37.8 % ) . The rates for disease-free survival and overall survival at 3 years were 48.3 % ( 95 % CI , 34.4%-60.8 % ) and 55.8 % ( 95 % CI , 41.6%-67.9 % ) , respectively . The median overall survival was 48.1 months ( 95 % CI , 29.6 months to not reached ) . Protocol -specified treatment-related grade 3 adverse events were reported in 7 patients ( 12.7 % ; 95 % CI , 9.6%-15.8 % ) ; grade 4 adverse events were reported in 2 patients ( 3.6 % ; 95 % CI , 2.7%-4.5 % ) . No grade 5 adverse events were reported . CONCLUSION Patients with inoperable non-small cell lung cancer who received stereotactic body radiation therapy had a survival rate of 55.8 % at 3 years , high rates of local tumor control , and moderate treatment-related morbidity BACKGROUND The combination of chemotherapy with thoracic radiotherapy ( TRT ) compared with TRT alone has been shown to confer a survival advantage for good performance status patients with stage III non-small cell lung cancer . However , it is not known whether sequential or concurrent delivery of these therapies is the optimal combination strategy . METHODS A total of 610 patients were r and omly assigned to two concurrent regimens and one sequential chemotherapy and TRT regimen in a three-arm phase III trial . The sequential arm included cisplatin at 100 mg/m2 on days 1 and 29 and vinblastine at 5 mg/m2 per week for 5 weeks with 63 Gy TRT delivered as once-daily fractions beginning on day 50 . Arm 2 used the same chemotherapy regimen as arm 1 with 63 Gy TRT delivered as once-daily fractions beginning on day 1 [ corrected ] . Arm 3 used cisplatin at 50 mg/m2 on days 1 , 8 , 29 , and 36 with oral etoposide at 50 mg twice daily for 10 weeks on days 1 , 2 , 5 , and 6 with 69.6 Gy delivered as 1.2 Gy twice-daily fractions beginning on day 1 . The primary endpoint was overall survival , and secondary endpoints included tumor response and time to tumor progression . Kaplan-Meier analyses were used to assess survival , and toxic effects were examined using the Wilcoxon rank sum test . All statistical tests were two-sided . RESULTS Median survival times were 14.6 , 17.0 , and 15.6 months for arms 1 - 3 , respectively . Five-year survival was statistically significantly higher for patients treated with the concurrent regimen with once-daily TRT compared with the sequential treatment ( 5-year survival : sequential , arm 1 , 10 % [ 20 patients ] , 95 % confidence interval [ CI ] = 7 % to 15 % ; concurrent , arm 2 , 16 % [ 31 patients ] , 95 % CI = 11 % to 22 % , P = .046 ; concurrent , arm 3 , 13 % [ 22 patients ] , 95 % CI = 9 % to 18 % ) . With a median follow-up time of 11 years , the rates of acute grade 3 - 5 nonhematologic toxic effects were higher with concurrent than sequential therapy , but late toxic effects were similar . CONCLUSION Concurrent delivery of cisplatin-based chemotherapy with TRT confers a long-term survival benefit compared with the sequential delivery of these therapies PURPOSE Phase I of Radiation Therapy Oncology Group ( RTOG ) 0117 determined that 74 Gy was the maximum-tolerated dose with concurrent weekly carboplatin/paclitaxel chemotherapy for inoperable non-small-cell lung cancer ( NSCLC ) . Phase II results are reported here . PATIENTS AND METHODS Patients with unresectable stages I-III NSCLC were eligible . Chemotherapy consisted of weekly paclitaxel at 50 mg/m(2 ) and carboplatin at area under the curve 2 mg/m(2 ) . The radiation dose was 74 Gy given in 37 fractions . Radiation therapy volumes included those of the gross tumor and involved nodes . The volume of lung at or exceeding 20 Gy ( V20 ) was m and ated to be < or= 30 % . RESULTS Of the combined phase I/II enrollment , a total of 55 patients received 74 Gy , of whom 53 were evaluable . The median follow-up was 19.3 months ( range , 0.9 to 57.9 months ) for all patients and 25.4 months ( range , 13.1 to 57.9 months ) for those still alive . The median survival for all patients was 25.9 months . The percentage surviving at least 12 months was 75.5 % ( 95 % CI , 65.7 % to 85.2 % ) . The median overall survival ( OS ) and progression-free survival ( PFS ) times for stage III patients ( n = 44 ) were 21.6 months and 10.8 months , respectively . OS and PFS rates at 12 months were 72.7 % and 50.0 % , respectively . Twelve patients experienced grade > or= 3 lung toxicity ( two patients had grade 5 lung toxicity ) . CONCLUSION The median survival time and OS rate at 12 months for this regimen are encouraging . These results serve as projection expectations for the high-dose radiation arms of the current RTOG 0617 phase III intergroup trial BACKGROUND Non small cell lung cancers ( NSCLC ) are rapidly proliferating tumours , which are characterized by the presence of extensive hypoxic components , especially in patients with advanced loco-regional disease . Previous studies suggest a deleterious impact of acute ( perfusion-limited ) hypoxia on the outcome of radiotherapy for these tumours . AIM This pilot study was aim ed at determining the feasibility and tumour response rates that can be achieved with an ARCON regime in patients with locally advanced , staged IIIA or B , NSCLC tumours . METHODS The phase I/II study included three steps : accelerated fractionation ( AF ) combined with carbogen  ( ten analysable patients ) , AF together with the daily administration of nicotinamide ( n = 11 ) and AF with both carbon and nicotinamide ( n = 14 ) . Radiotherapy was based on a large daily dose per fraction ( 2.75 Gy up to 55 Gy in 4 weeks ) . Nicotinamide was administered at a dose of 6 g per patient per treatment day and carbogen was inhaled for 5 min before and during radiotherapy . RESULTS The incidence of grade 3 + acute toxicity during the irradiation did not exceed 10 % , neither in the lung parenchyma nor in the mediastinum . No significant difference was found in loco-regional , radio-induced toxicity among the three study steps . Although a similar fraction of patients showed grade 2 or 3 emesis in all the steps , of the 25 patients entered in the two Nicotinamide containing steps 10 ( 40 % ) developed grade 2 or greater reactions which significantly detracted from their quality of life . There was no significant difference in tumour clearance rate among the three steps . The percentage of objective responses at 2 months was 60 , 54 and 57 % in steps 1 , 2 and 3 , respectively . CONCLUSION The feasibility of this ARCON protocol , using 2.75 Gy doses per fraction over 4 weeks , is good as regards radiotherapy-related side effects but it appears necessary in future to reduce the dose of Nicotinamide to reduce the incidence of nausea and vomiting . There was no significant difference in time to progression among the three study steps BACKGROUND Combined radiochemotherapy is the gold st and ard for patients with locally advanced non-small cell lung cancer ( LA-NSCLC ) . In the present study , the feasibility of hypofractionated accelerated radiotherapy with cytoprotection ( HypoARC ) in combination with vinorelbine and liposomal doxorubicin was evaluated . PATIENTS AND METHODS Fourteen patients ( pts ) with LA-NSCLC ( PS 0 - 2 ) were recruited . Patients received 15 fractions for 3.5 Gy within four consecutive weeks ( 1 week split after the 10th fraction ) , supported with subcutaneously administered amifostine ( 500 - 1000 mg/day ) . Pegylated liposomal doxorubicin was administered at a st and ard dose of 20 mg/m2 every two weeks , for 3 consecutive cycles . Vinorelbine was administered at 3 dose levels : a ) 20 mg/m2 every week ( 5 pts ) , b ) 25 mg/m2 thrice every two weeks ( 5 pts ) and c ) 30 mg/m2 thrice every two weeks ( 4 pts ) . RESULTS Grade 3 neutropenia enforcing chemotherapy delays was noted in 2/5 and 2/4 patients in the groups b and c respectively . Fatigue was a common but not dose-defining feature . Radiation grade 2 esophagitis was noted in 6/14 patients . No case of severe radiation pneumonitis was noted . Partial response was documented in 9/14 patients , minimal response in 3/14 and stable disease in 2/14 . The median local progression-free survival was 12 months and the median overall survival was 8 months . CONCLUSION It is concluded that the administration of 25 mg/m2 of vinorelbine thrice a week together with liposomal doxorubicin and thoracic radiotherapy is feasible for patients with LA-NSCLC , providing high response rates . Further studies are required to better assess benefits in terms of local and distant control of the disease Introduction : Long-term results of a phase II study on the use of induction chemotherapy ( CHT ) using paclitaxel (P)-carboplatin ( C ) followed by a concurrent radiation therapy ( RT ) and weekly P and consolidation PC were review ed . Patients and Methods : Thirty-two patients with stage III non-small cell lung cancer started treatment with induction CHT  ( two cycles of P 175 mg/m2 , day 1 and C , area under the curve 6 , day 1 , given at 3-week interval ) , after which accelerated RT with a concomitant boost ( “ field-in-a-field ” ) ( 1.8 Gy large fields and the boost dose 0.88 Gy ) was administered in 23 fractions with 61.64 Gy and concurrent weekly P ( 45 mg/m2 ) . Consolidation with two cycles of PC was administered . Results : The median follow-up for all 32 patients was 17.2 months ( range , 3.8 - 107 months ) . The median survival time was 16.9 months , and the 5-year survival and 10-year survival were 25 % and 17.5 % , respectively . The median time for disease progression was 9.5 months , and disease-free survival was 21 % at 5 and 10 years . The median time to local progression was 14.6 months , and the 5- to 10-year local progression-free survival was 35.7 % . The median time to distant metastasis was 17.5 months . Toxicity was acceptable , with only one ( 3.1 % ) patient experiencing grade 5 ( lung ) toxicity and another patient presenting grade 4 toxicity ( leucopenia ) . Conclusions : The results of this single-institutional phase II study of induction CHT followed by concurrent RT-CHT and consolidation CHT in very unfavorable patient population showed acceptable results with acceptable toxicity BACKGROUND Many patients with locally advanced non-small cell lung cancer ( NSCLC ) can not undergo concurrent chemotherapy because of comorbidities or poor performance status . Hypofractionated radiation regimens , if tolerable , may provide an option to these patients for effective local control . METHODS AND MATERIAL S Twenty-five patients were enrolled in a phase 1 dose-escalation trial of proton beam therapy ( PBT ) from September 2010 through July 2012 . Eligible patients had histologically documented lung cancer , thymic tumors , carcinoid tumors , or metastatic thyroid tumors .  Concurrent chemotherapy was not allowed , but concurrent treatment with biologic agents was . The dose-escalation schema comprised 15 fractions of 3 Gy(relative biological effectiveness [RBE])/fraction , 3.5 Gy(RBE)/fraction , or 4 Gy(RBE)/fraction . Dose constraints were derived from biologically equivalent doses of st and ard fractionated treatment . RESULTS The median follow-up time for patients alive at the time of analysis was 13 months ( range , 8 - 28 months ) . Fifteen patients received treatment to hilar or mediastinal lymph nodes . Two patients experienced dose-limiting toxicity possibly related to treatment ; 1 received 3.5-Gy(RBE ) fractions and experienced an in-field tracheoesophageal fistula 9 months after PBT and 1 month after bevacizumab . The other patient received 4-Gy(RBE ) fractions and was hospitalized for bacterial pneumonia/radiation pneumonitis 4 months after PBT . CONCLUSION Hypofractionated PBT to the thorax delivered over 3 weeks was well tolerated even with significant doses to the lungs and mediastinal structures . Phase 2/3 trials are needed to compare the efficacy of this technique with st and ard treatment for locally advanced NSCLC BACKGROUND Continuous hyperfractionated accelerated radiotherapy ( CHART ) counteracts re population and may significantly improve outcome of patients with non-small-cell lung cancer ( NSCLC ) . Nevertheless high local failure rates call for radiation dose escalation . We report here the final results of the multicentric CHARTWEL trial ( CHART weekend less , ARO 97 - 1 ) . PATIENTS AND METHODS Four hundred and six patients with NSCLC were stratified according to stage , histology , neoadjuvant chemotherapy and centre and were r and omized to receive 3D-planned radiotherapy to 60Gy/40 fractions/2.5weeks ( CHARTWEL ) or 66Gy/33 fractions/6.5weeks ( conventional fractionation , CF ) . RESULTS Overall survival ( OS , primary endpoint ) at 2 , 3 and 5yr was not significantly different after CHARTWEL ( 31 % , 22 % and 11 % ) versus CF ( 32 % , 18 % and 7 % ; HR 0.92 , 95 % CI 0.75 - 1.13 , p=0.43 ) . Also local tumour control rates and distant metastases did not significantly differ . Acute dysphagia and radiological pneumonitis were more pronounced after CHARTWEL , without differences in clinical signs of pneumopathy . Exploratory analysis revealed a significant trend for improved LC after CHARTWEL versus CF with increasing UICC , T or N stage ( p=0.006 - 0.025 ) and after neoadjuvant chemotherapy ( HR 0.48 , 0.26 - 0.89 , p=0.019 ) . CONCLUSIONS Overall , outcome after CHARTWEL or CF was not different . The lower total dose in the CHARTWEL arm was compensated by the shorter overall treatment time , confirming a time factor for NSCLC . The higher efficacy of CHARTWEL versus CF in advanced stages and after chemotherapy provides a basis for further trials on treatment intensification for locally advanced NSCLC BACKGROUND Modest benefits from concurrent chemoradiotherapy in patients with locally advanced NSCLC warrant further clinical investigations to identify more effective treatment regimens . Cetuximab , a monoclonal antibody against the epidermal growth factor receptor has shown activity in NSCLC . We report on the safety and efficacy of the combination of daily dose Cisplatin and concurrent radiotherapy with or without weekly Cetuximab . PATIENTS AND METHODS Patients received high dose accelerated radiotherapy ( 66 Gy in 24 fractions ) and concurrent daily Cisplatin ( 6 mg/m(2 ) ) without ( Arm A ) or with ( Arm B ) weekly Cetuximab ( 400 mg/m(2 ) loading dose one week prior to radiotherapy followed by weekly 250 mg/m(2 ) ) . The primary endpoint of the trial was objective local control rate ( OLCR ) determined at 6 - 8 weeks after treatment . Toxicity was reported as well . RESULTS Between February 2009 and May 2011 , 102 patients were r and omized . Median follow up was 29 months . The OLCR was 84 % in Arm A and 92 % in Arm B ( p=0.36 ) . The one-year local progression free interval ( LPFI ) and overall survival ( OS ) were 69 % and 82 % for Arm A and 73 % and 71 % for Arm B , respectively ( LPFI p=0.39 ; OS p=0.99 ) . Toxicity compared equally between both groups . CONCLUSION The addition of Cetuximab to radiotherapy and concurrent Cisplatin did not improve disease control in patients with locally advanced NSCLC but increased treatment related toxicity
PURPOSE To identify survival and toxicity characteristics associated with radical-intent hypofractionated radiotherapy for the treatment of stage III non-small-cell lung cancer ( NSCLC ) .