human
***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: We carried out a prospect i ve phase II study of patients with limited stage small cell lung cancer ( LS-SCLC ) assigned to receive stereotactic body radiotherapy ( SBRT ) concurrently with cisplatin-based chemotherapeutic regimen with OS and PFS as the primary study endpoints . Patients with pathologically proven LS-SCLC received 4–6 cycles of cisplatin 75 mg/(m2/day ) given intravenously on day 1 and etoposide 80 mg/(m2/day ) given intravenously on days 1–5 , both at 3 weekly intervals . SBRT at a dose of 4,000–4,500 cGy in ten fractions was given concurrently with chemotherapy starting on day 1 . The Kaplan – Meier curve and life tables were used to describe survival data . Adverse events were evaluated according to the common terminology criteria for adverse events version of the radiation therapy oncology group ( RTOG ) . Twenty-nine patients were included and followed up for a median duration of 19 ( range 10–85 ) months . The median OS was 27 ( 95 % CI 20.2–33.8 ) months . The median PFS was 12 ( 95 % CI 4.2–19.8 ) months . No grade 4 adverse events were observed . Grade 3 adverse events occurred in only 5 ( 13.8 % , 5/29 ) patients . Neutropenia of any grade was observed in 6 ( 15 % , 6/29 ) patients , with grade 3 neutropenia only seen in one ( 3.4 % , 1/29 ) patient . The combination of chemotherapy and early concurrent SBRT could be a safe and effective treatment for LS-SCLC patients . Our study confirmed that SBRT with concurrent chemotherapy is another new treatment option for LS-SCLC patients The purpose of this study was to evaluate the treatment outcomes of stereotactic body radiotherapy ( SBRT ) for Stage I small-cell lung cancer ( SCLC ) . From April 2003 to September 2009 , a total of eight patients with Stage I SCLC were treated with SBRT in our institution . In all patients , the lung tumors were proven as SCLC pathologically . The patients ' ages were 58–84 years ( median : 74 ) . The T-stage of the primary tumor was T1a in two , T1b in two and T2a in four patients . Six of the patients were inoperable because of poor cardiac and /or pulmonary function , and two patients refused surgery . SBRT was given using 7–8 non-coplanar beams with 48 Gy in four fractions . Six of the eight patients received 3–4 cycles of chemotherapy using carboplatin ( CBDCA ) + etoposide ( VP-16 ) or cisplatin ( CDDP ) + irinotecan ( CPT-11 ) . The follow-up period for all patients was 6–60 months ( median : 32 ) . Six patients were still alive without any recurrence . One patient died from this disease and one died from another disease . The overall and disease-specific survival rate at three years was 72 % and 86 % , respectively . There were no patients with local progression of the lesion targeted by SBRT . Only one patient had nodal recurrence in the mediastinum at 12 months after treatment . The progression-free survival rate was 71 % . No Grade 2 or higher SBRT-related toxicities were observed . SBRT plus chemotherapy could be an alternative to surgery with chemotherapy for inoperable patients with Stage I small-cell lung cancer . However , further investigation is needed using a large series of patients The Lung Cancer Study Group of the International Society of Chemotherapy ( ISC-LCSG ) organized multinational , cooperative , prospect i ve and r and omized trials for the cure of patients with small cell lung cancer at early stages ( T1,2N0M0 ) . Surgery for cure was used first , followed by postoperative chemotherapy , and thereafter by prophylactic cranial irradiation . Eight cycles of st and ard chemotherapy ( CAV-cyclophosphamide-doxorubicin-vincristine ) or 6 intermittent cycles of alternating chemotherapy , using 3 different drug combinations , were administered 1 - 2 weeks postoperatively for 6 months after r and omization . A total of 183 evaluable patients received surgery for cure at 23 cooperating hospitals . The preliminary evaluation of ISC- studies I and II per May 1993 result ed in the 30-month total survival of 63 % from 68 patients after complete resection at TN0M0R0-stages and 37 % from 27 patients after such resections at TN2M0R0-stages . Their incidence of local recurrence as first relapse was quite similar ( 11/47:8/39 ) . The related 4-year recurrence-free survival ( 57 % , 37 % ) , indicating a plateau-like curve of long-term survivors . These promising results have to be confirmed by larger studies . We conclude that the indication for surgery as the first treatment step for SCLC should be the same as for the other non-small subtypes of lung cancers Introduction Concurrent ONce-daily VErsus twice-daily RadioTherapy ( CONVERT ) is the only multicentre , international , r and omised , phase III trial open in Europe and Canada looking at optimisation of chemoradiotherapy ( RT ) in limited stage small cell lung cancer ( LS-SCLC ) . Following on from the Turrisi trial of once-daily versus twice-daily ( BD ) concurrent chemoradiotherapy , there is a real need for a new phase III trial using modern conformal RT techniques and investigating higher once-daily radiation dose . This trial has the potential to define a new st and ard chemo-RT regimen for patients with LS-SCLC and good performance status . Methods and analysis 447 patients with histologically or cytologically proven diagnosis of SCLC were recruited from 74 centres in eight countries between 2008 and 2013 . Patients were r and omised to receive either concurrent twice-daily RT(45 Gy in 30 twice-daily fractions over 3 weeks ) or concurrent once-daily RT(66 Gy in 33 once-daily fractions over 6.5 weeks ) both starting on day 22 of cycle 1 . Patients are followed up until death . The primary end point of the study is overall survival and secondary end points include local progression-free survival , metastasis-free survival , acute and late toxicity based on the Common Terminology Criteria for Adverse Events V.3.0 , chemotherapy and RTdose intensity . Ethics and dissemination The trial received ethical approval from NRES Committee North West — Greater Manchester Central ( 07/H1008/229 ) . There is a trial steering committee , including independent members and an independent data monitoring committee . Results will be published in a peer- review ed journal and presented at international conferences . Trial registration number IS RCT N91927162 ; Pre- results Summary Background Concurrent chemoradiotherapy is the st and ard of care in limited-stage small-cell lung cancer , but the optimal radiotherapy schedule and dose remains controversial . The aim of this study was to establish a st and ard chemoradiotherapy treatment regimen in limited-stage small-cell lung cancer . Methods The CONVERT trial was an open-label , phase 3 , r and omised superiority trial . We enrolled adult patients ( aged ≥18 years ) who had cytologically or histologically confirmed limited-stage small-cell lung cancer , Eastern Cooperative Oncology Group performance status of 0–2 , and adequate pulmonary function . Patients were recruited from 73 centres in eight countries . Patients were r and omly assigned to receive either 45 Gy radiotherapy in 30 twice-daily fractions of 1·5 Gy over 19 days , or 66 Gy in 33 once-daily fractions of 2 Gy over 45 days , starting on day 22 after commencing cisplatin – etoposide chemotherapy ( given as four to six cycles every 3 weeks in both groups ) . The allocation method used was minimisation with a r and om element , stratified by institution , planned number of chemotherapy cycles , and performance status . Treatment group assignments were not masked . The primary endpoint was overall survival , defined as time from r and omisation until death from any cause , analysed by modified intention-to-treat . A 12 % higher overall survival at 2 years in the once-daily group versus the twice-daily group was considered to be clinical ly significant to show superiority of the once-daily regimen . The study is registered with Clinical Trials.gov ( NCT00433563 ) and is currently in follow-up . Findings Between April 7 , 2008 , and Nov 29 , 2013 , 547 patients were enrolled and r and omly assigned to receive twice-daily concurrent chemoradiotherapy ( 274 patients ) or once-daily concurrent chemoradiotherapy ( 273 patients ) . Four patients ( one in the twice-daily group and three in the once-daily group ) did not return their case report forms and were lost to follow-up ; these patients were not included in our analyses . At a median follow-up of 45 months ( IQR 35–58 ) , median overall survival was 30 months ( 95 % CI 24–34 ) in the twice-daily group versus 25 months ( 21–31 ) in the once-daily group ( hazard ratio for death in the once daily group 1·18 [ 95 % CI 0·95–1·45 ] ; p=0·14 ) . 2-year overall survival was 56 % ( 95 % CI 50–62 ) in the twice-daily group and 51 % ( 45–57 ) in the once-daily group ( absolute difference between the treatment groups 5·3 % [ 95 % CI −3·2 % to 13·7 % ] ) . The most common grade 3–4 adverse event in patients evaluated for chemotherapy toxicity was neutropenia ( 197 [ 74 % ] of 266 patients in the twice-daily group vs 170 [ 65 % ] of 263 in the once-daily group ) . Most toxicities were similar between the groups , except there was significantly more grade 4 neutropenia with twice-daily radiotherapy ( 129 [ 49 % ] vs 101 [ 38 % ] ; p=0·05 ) . In patients assessed for radiotherapy toxicity , was no difference in grade 3–4 oesophagitis between the groups ( 47 [ 19 % ] of 254 patients in the twice-daily group vs 47 [ 19 % ] of 246 in the once-daily group ; p=0·85 ) and grade 3–4 radiation pneumonitis ( 4 [ 3 % ] of 254 vs 4 [ 2 % ] of 246 ; p=0·70 ) . 11 patients died from treatment-related causes ( three in the twice-daily group and eight in the once-daily group ) . Interpretation Survival outcomes did not differ between twice-daily and once-daily concurrent chemoradiotherapy in patients with limited-stage small-cell lung cancer , and toxicity was similar and lower than expected with both regimens . Since the trial was design ed to show superiority of once-daily radiotherapy and was not powered to show equivalence , the implication is that twice-daily radiotherapy should continue to be considered the st and ard of care in this setting . Funding Cancer Research UK ( Clinical Trials Awards and Advisory Committee ) , French Ministry of Health , Canadian Cancer Society Research Institute , European Organisation for Research and Treatment of Cancer ( Cancer Research Fund , Lung Cancer , and Radiation Oncology Groups ) Background Although T1‐T2N0 non – small cell lung cancer can be managed with stereotactic body radiotherapy ( SBRT ) alone , this management has often been extrapolated to T1‐T2N0 small cell lung cancer ( SCLC ) . This secondary analysis of a multi‐institutional cohort study investigated whether the addition of chemotherapy and prophylactic cranial irradiation ( PCI ) improved the outcomes for these patients . Material s and Methods All cases of histologically confirmed T1‐T2N0M0 SCLC were obtained from 24 institutions ' prospect ively collected SBRT data bases . The clinical and treatment characteristics , toxicities , outcomes , and patterns of failure were assessed . We used Kaplan‐Meier analysis to evaluate the survival outcomes . Univariate and multivariate analyses identified the predictors of outcomes . Results From 24 institutions , 76 lesions were treated in 74 patients ( median follow‐up , 18 months ) . Chemotherapy and PCI were delivered in 56 % and 23 % of cases , respectively . The median SBRT dose per fraction was 50 Gy/5 fractions . Patients receiving chemotherapy experienced increased median disease‐free survival ( 61.3 vs. 9.0 months ; P = .02 ) and overall survival ( 31.4 vs. 14.3 months ; P = .02 ) . Chemotherapy independently predicted for better outcomes for disease‐free survival and overall survival on multivariate analysis ( P = .01 ) . Toxicities were uncommon ; 5.2 % experienced grade ≥ 2 pneumonitis . Post‐treatment failures were most commonly distant ( 45.8 % of recurrences ) , followed by nodal ( 25.0 % ) , and elsewhere in the lung ( 20.8 % ) . The median time to each was 5 to 7 months . Conclusion Patients undergoing primary SBRT for T1‐T2N0 SCLC should also undergo additional chemotherapy . No established role was found for PCI in this population . Micro‐ Abstract T1‐T2N0 
    Output:
    
agent
***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: We carried out a prospect i ve phase II study of patients with limited stage small cell lung cancer ( LS-SCLC ) assigned to receive stereotactic body radiotherapy ( SBRT ) concurrently with cisplatin-based chemotherapeutic regimen with OS and PFS as the primary study endpoints . Patients with pathologically proven LS-SCLC received 4–6 cycles of cisplatin 75 mg/(m2/day ) given intravenously on day 1 and etoposide 80 mg/(m2/day ) given intravenously on days 1–5 , both at 3 weekly intervals . SBRT at a dose of 4,000–4,500 cGy in ten fractions was given concurrently with chemotherapy starting on day 1 . The Kaplan – Meier curve and life tables were used to describe survival data . Adverse events were evaluated according to the common terminology criteria for adverse events version of the radiation therapy oncology group ( RTOG ) . Twenty-nine patients were included and followed up for a median duration of 19 ( range 10–85 ) months . The median OS was 27 ( 95 % CI 20.2–33.8 ) months . The median PFS was 12 ( 95 % CI 4.2–19.8 ) months . No grade 4 adverse events were observed . Grade 3 adverse events occurred in only 5 ( 13.8 % , 5/29 ) patients . Neutropenia of any grade was observed in 6 ( 15 % , 6/29 ) patients , with grade 3 neutropenia only seen in one ( 3.4 % , 1/29 ) patient . The combination of chemotherapy and early concurrent SBRT could be a safe and effective treatment for LS-SCLC patients . Our study confirmed that SBRT with concurrent chemotherapy is another new treatment option for LS-SCLC patients The purpose of this study was to evaluate the treatment outcomes of stereotactic body radiotherapy ( SBRT ) for Stage I small-cell lung cancer ( SCLC ) . From April 2003 to September 2009 , a total of eight patients with Stage I SCLC were treated with SBRT in our institution . In all patients , the lung tumors were proven as SCLC pathologically . The patients ' ages were 58–84 years ( median : 74 ) . The T-stage of the primary tumor was T1a in two , T1b in two and T2a in four patients . Six of the patients were inoperable because of poor cardiac and /or pulmonary function , and two patients refused surgery . SBRT was given using 7–8 non-coplanar beams with 48 Gy in four fractions . Six of the eight patients received 3–4 cycles of chemotherapy using carboplatin ( CBDCA ) + etoposide ( VP-16 ) or cisplatin ( CDDP ) + irinotecan ( CPT-11 ) . The follow-up period for all patients was 6–60 months ( median : 32 ) . Six patients were still alive without any recurrence . One patient died from this disease and one died from another disease . The overall and disease-specific survival rate at three years was 72 % and 86 % , respectively . There were no patients with local progression of the lesion targeted by SBRT . Only one patient had nodal recurrence in the mediastinum at 12 months after treatment . The progression-free survival rate was 71 % . No Grade 2 or higher SBRT-related toxicities were observed . SBRT plus chemotherapy could be an alternative to surgery with chemotherapy for inoperable patients with Stage I small-cell lung cancer . However , further investigation is needed using a large series of patients The Lung Cancer Study Group of the International Society of Chemotherapy ( ISC-LCSG ) organized multinational , cooperative , prospect i ve and r and omized trials for the cure of patients with small cell lung cancer at early stages ( T1,2N0M0 ) . Surgery for cure was used first , followed by postoperative chemotherapy , and thereafter by prophylactic cranial irradiation . Eight cycles of st and ard chemotherapy ( CAV-cyclophosphamide-doxorubicin-vincristine ) or 6 intermittent cycles of alternating chemotherapy , using 3 different drug combinations , were administered 1 - 2 weeks postoperatively for 6 months after r and omization . A total of 183 evaluable patients received surgery for cure at 23 cooperating hospitals . The preliminary evaluation of ISC- studies I and II per May 1993 result ed in the 30-month total survival of 63 % from 68 patients after complete resection at TN0M0R0-stages and 37 % from 27 patients after such resections at TN2M0R0-stages . Their incidence of local recurrence as first relapse was quite similar ( 11/47:8/39 ) . The related 4-year recurrence-free survival ( 57 % , 37 % ) , indicating a plateau-like curve of long-term survivors . These promising results have to be confirmed by larger studies . We conclude that the indication for surgery as the first treatment step for SCLC should be the same as for the other non-small subtypes of lung cancers Introduction Concurrent ONce-daily VErsus twice-daily RadioTherapy ( CONVERT ) is the only multicentre , international , r and omised , phase III trial open in Europe and Canada looking at optimisation of chemoradiotherapy ( RT ) in limited stage small cell lung cancer ( LS-SCLC ) . Following on from the Turrisi trial of once-daily versus twice-daily ( BD ) concurrent chemoradiotherapy , there is a real need for a new phase III trial using modern conformal RT techniques and investigating higher once-daily radiation dose . This trial has the potential to define a new st and ard chemo-RT regimen for patients with LS-SCLC and good performance status . Methods and analysis 447 patients with histologically or cytologically proven diagnosis of SCLC were recruited from 74 centres in eight countries between 2008 and 2013 . Patients were r and omised to receive either concurrent twice-daily RT(45 Gy in 30 twice-daily fractions over 3 weeks ) or concurrent once-daily RT(66 Gy in 33 once-daily fractions over 6.5 weeks ) both starting on day 22 of cycle 1 . Patients are followed up until death . The primary end point of the study is overall survival and secondary end points include local progression-free survival , metastasis-free survival , acute and late toxicity based on the Common Terminology Criteria for Adverse Events V.3.0 , chemotherapy and RTdose intensity . Ethics and dissemination The trial received ethical approval from NRES Committee North West — Greater Manchester Central ( 07/H1008/229 ) . There is a trial steering committee , including independent members and an independent data monitoring committee . Results will be published in a peer- review ed journal and presented at international conferences . Trial registration number IS RCT N91927162 ; Pre- results Summary Background Concurrent chemoradiotherapy is the st and ard of care in limited-stage small-cell lung cancer , but the optimal radiotherapy schedule and dose remains controversial . The aim of this study was to establish a st and ard chemoradiotherapy treatment regimen in limited-stage small-cell lung cancer . Methods The CONVERT trial was an open-label , phase 3 , r and omised superiority trial . We enrolled adult patients ( aged ≥18 years ) who had cytologically or histologically confirmed limited-stage small-cell lung cancer , Eastern Cooperative Oncology Group performance status of 0–2 , and adequate pulmonary function . Patients were recruited from 73 centres in eight countries . Patients were r and omly assigned to receive either 45 Gy radiotherapy in 30 twice-daily fractions of 1·5 Gy over 19 days , or 66 Gy in 33 once-daily fractions of 2 Gy over 45 days , starting on day 22 after commencing cisplatin – etoposide chemotherapy ( given as four to six cycles every 3 weeks in both groups ) . The allocation method used was minimisation with a r and om element , stratified by institution , planned number of chemotherapy cycles , and performance status . Treatment group assignments were not masked . The primary endpoint was overall survival , defined as time from r and omisation until death from any cause , analysed by modified intention-to-treat . A 12 % higher overall survival at 2 years in the once-daily group versus the twice-daily group was considered to be clinical ly significant to show superiority of the once-daily regimen . The study is registered with Clinical Trials.gov ( NCT00433563 ) and is currently in follow-up . Findings Between April 7 , 2008 , and Nov 29 , 2013 , 547 patients were enrolled and r and omly assigned to receive twice-daily concurrent chemoradiotherapy ( 274 patients ) or once-daily concurrent chemoradiotherapy ( 273 patients ) . Four patients ( one in the twice-daily group and three in the once-daily group ) did not return their case report forms and were lost to follow-up ; these patients were not included in our analyses . At a median follow-up of 45 months ( IQR 35–58 ) , median overall survival was 30 months ( 95 % CI 24–34 ) in the twice-daily group versus 25 months ( 21–31 ) in the once-daily group ( hazard ratio for death in the once daily group 1·18 [ 95 % CI 0·95–1·45 ] ; p=0·14 ) . 2-year overall survival was 56 % ( 95 % CI 50–62 ) in the twice-daily group and 51 % ( 45–57 ) in the once-daily group ( absolute difference between the treatment groups 5·3 % [ 95 % CI −3·2 % to 13·7 % ] ) . The most common grade 3–4 adverse event in patients evaluated for chemotherapy toxicity was neutropenia ( 197 [ 74 % ] of 266 patients in the twice-daily group vs 170 [ 65 % ] of 263 in the once-daily group ) . Most toxicities were similar between the groups , except there was significantly more grade 4 neutropenia with twice-daily radiotherapy ( 129 [ 49 % ] vs 101 [ 38 % ] ; p=0·05 ) . In patients assessed for radiotherapy toxicity , was no difference in grade 3–4 oesophagitis between the groups ( 47 [ 19 % ] of 254 patients in the twice-daily group vs 47 [ 19 % ] of 246 in the once-daily group ; p=0·85 ) and grade 3–4 radiation pneumonitis ( 4 [ 3 % ] of 254 vs 4 [ 2 % ] of 246 ; p=0·70 ) . 11 patients died from treatment-related causes ( three in the twice-daily group and eight in the once-daily group ) . Interpretation Survival outcomes did not differ between twice-daily and once-daily concurrent chemoradiotherapy in patients with limited-stage small-cell lung cancer , and toxicity was similar and lower than expected with both regimens . Since the trial was design ed to show superiority of once-daily radiotherapy and was not powered to show equivalence , the implication is that twice-daily radiotherapy should continue to be considered the st and ard of care in this setting . Funding Cancer Research UK ( Clinical Trials Awards and Advisory Committee ) , French Ministry of Health , Canadian Cancer Society Research Institute , European Organisation for Research and Treatment of Cancer ( Cancer Research Fund , Lung Cancer , and Radiation Oncology Groups ) Background Although T1‐T2N0 non – small cell lung cancer can be managed with stereotactic body radiotherapy ( SBRT ) alone , this management has often been extrapolated to T1‐T2N0 small cell lung cancer ( SCLC ) . This secondary analysis of a multi‐institutional cohort study investigated whether the addition of chemotherapy and prophylactic cranial irradiation ( PCI ) improved the outcomes for these patients . Material s and Methods All cases of histologically confirmed T1‐T2N0M0 SCLC were obtained from 24 institutions ' prospect ively collected SBRT data bases . The clinical and treatment characteristics , toxicities , outcomes , and patterns of failure were assessed . We used Kaplan‐Meier analysis to evaluate the survival outcomes . Univariate and multivariate analyses identified the predictors of outcomes . Results From 24 institutions , 76 lesions were treated in 74 patients ( median follow‐up , 18 months ) . Chemotherapy and PCI were delivered in 56 % and 23 % of cases , respectively . The median SBRT dose per fraction was 50 Gy/5 fractions . Patients receiving chemotherapy experienced increased median disease‐free survival ( 61.3 vs. 9.0 months ; P = .02 ) and overall survival ( 31.4 vs. 14.3 months ; P = .02 ) . Chemotherapy independently predicted for better outcomes for disease‐free survival and overall survival on multivariate analysis ( P = .01 ) . Toxicities were uncommon ; 5.2 % experienced grade ≥ 2 pneumonitis . Post‐treatment failures were most commonly distant ( 45.8 % of recurrences ) , followed by nodal ( 25.0 % ) , and elsewhere in the lung ( 20.8 % ) . The median time to each was 5 to 7 months . Conclusion Patients undergoing primary SBRT for T1‐T2N0 SCLC should also undergo additional chemotherapy . No established role was found for PCI in this population . Micro‐ Abstract T1‐T2N0 
    Output:
    