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: PURPOSE This Phase II trial evaluated the toxicity , local control , and overall survival in patients treated with sequential gemcitabine and linear accelerator-based single-fraction stereotactic body radiotherapy ( SBRT ) .  METHODS AND MATERIAL S Twenty patients with locally advanced , nonmetastatic pancreatic adenocarcinoma were enrolled on this prospect i ve single-institution , institutional review board-approved study . Gemcitabine was administered on Days 1 , 8 , and 15 , and SBRT on Day 29 . Gemcitabine was restarted on Day 43 and continued for 3 - 5 cycles . SBRT of 25 Gy in a single fraction was delivered to the internal target volume with a 2- 3-mm margin using a nine-field intensity-modulated radiotherapy technique . Respiratory gating was used to account for breathing motion . Follow-up evaluations occurred at 4 - 6 weeks , 10 - 12 weeks , and every 3 months after SBRT . RESULTS All patients completed SBRT and a median of five cycles of chemotherapy . Follow-up for the 2 remaining alive patients was 25.1 and 36.4 months . No acute Grade 3 or greater nonhematologic toxicity was observed . Late Grade 3 or greater toxicities occurred in 1 patient ( 5 % ) and consisted of a duodenal perforation ( G4 ) . Three patients ( 15 % ) developed ulcers ( G2 ) that were medically managed . Overall , median survival was 11.8 months , with 1-year survival of 50 % and 2-year survival of 20 % . Using serial computed tomography , the freedom from local progression was 94 % at 1 year . CONCLUSION Linear accelerator-delivered SBRT with sequential gemcitabine result ed in excellent local control of locally advanced pancreatic cancer . Future studies will address strategies for reducing long-term duodenal toxicity associated with SBRT PURPOSE This phase III trial compared the efficacy and safety of gemcitabine ( Gem ) plus capecitabine ( GemCap ) versus single-agent Gem in advanced/metastatic pancreatic cancer . PATIENTS AND METHODS Patients were r and omly assigned to receive GemCap ( oral capecitabine 650 mg/m2 twice daily on days 1 to 14 plus Gem 1,000 mg/m2 by 30-minute infusion on days 1 and 8 every 3 weeks ) or Gem ( 1,000 mg/m2 by 30-minute infusion weekly for 7 weeks , followed by a 1-week break , and then weekly for 3 weeks every 4 weeks ) . Patients were stratified according to center , Karnofsky performance score ( KPS ) , presence of pain , and disease extent . RESULTS A total of 319 patients were enrolled between June 2001 and June 2004 .  Median overall survival ( OS ) time , the primary end point , was 8.4 and 7.2 months in the GemCap and Gem arms , respectively ( P = .234 ) . Post hoc analysis in patients with good KPS ( score of 90 to 100 ) showed a significant prolongation of median OS time in the GemCap arm compared with the Gem arm ( 10.1 v 7.4 months , respectively ; P = .014 ) . The overall frequency of grade 3 or 4 adverse events was similar in each arm . Neutropenia was the most frequent grade 3 or 4 adverse event in both arms . CONCLUSION GemCap failed to improve OS at a statistically significant level compared with st and ard Gem treatment . The safety of GemCap and Gem was similar . In the subgroup of patients with good performance status , median OS was improved significantly . GemCap is a practical regimen that may be considered as an alternative to single-agent Gem for the treatment of advanced/metastatic pancreatic cancer patients with a good performance status CONTEXT Sympathectomy is currently used as the fourth step of the modified World Health Organization ( WHO ) analgesic ladder . Sympathectomy can be performed early , before the second step on the ladder . OBJECTIVES We hypothesized that early sympathectomy would reduce pain and opioid consumption and improve quality of life . METHODS One hundred nine patients , with inoperable abdominal or pelvic cancer , reporting visceral pain of 40 - 70 on a visual analogue scale and taking nonopioid analgesics  were allocated r and omly into two groups : either blocks were performed before Step 2 of the WHO ladder , then analgesics were managed according to the ladder ( Group I ) or analgesics were given according to the WHO ladder , and blocks were performed as the fourth step after failure of strong opioids to control pain ( Group II ) . Visual analogue scale scores , responder analysis , daily opioid consumption , related side effects , and quality of life were assessed . RESULTS Responders were significantly higher in Group I ( P < 0.0001 ) , and partial responders and nonresponders significantly increased in Group II ( P < 0.0001 and 0.006 , respectively ) . Opioid consumption significantly decreased in Group I ( P < 0.0001 during first 12 months and 0.007 at the last assessment time ) , with concomitant significant reduction in related side effects . The number of patients who had a good analgesic response on tramadol significantly increased in Group I during the first five months ( P < 0.05 ) . European Organization for Research and Treatment of Cancer Quality of Life Question naire-Core 30 global quality -of-life subscale scores revealed significant improvement until the fifth month in Group I ( P < 0.05 ) . CONCLUSION Sympathectomy before Step 2 on the WHO analgesic ladder seems to lead to better pain control , less opioid consumption , and better quality of life in cancer patients Purpose Chemoradiation therapy ( CRT ) for patients with locally advanced pancreatic cancer ( LAPC ) provides survival benefits but may result in considerable toxicity . Health-related quality of life ( HRQL ) measurements during CRT have not been widely reported . This paper reports HRQL data from the Selective Chemoradiation in Advanced Localised Pancreatic Cancer ( SCALOP ) trial , including validation of the QLQ-PAN26 tool in CRT . Methods and Material s Patients with locally advanced , inoperable , nonmetastatic carcinoma of the pancreas were eligible . Following 12 weeks of induction gemcitabine plus capecitabine ( GEMCAP ) chemotherapy , patients with stable and responding disease were r and omized to a further cycle of GEMCAP followed by capecitabine- or gemcitabine-based CRT .  HRQL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-C30 ) and the EORTC Pancreatic Cancer module ( PAN26 ) . Results A total of 114 patients from 28 UK centers were registered and 74 patients r and omized . There was improvement in the majority of HRQL scales during induction chemotherapy . Patients with significant deterioration in fatigue , appetite loss , and gastrointestinal symptoms during CRT recovered within 3 weeks following CRT . Differences in changes in HRQL scores between trial arms rarely reached statistical significance ; however , where they did , they favored capecitabine therapy . PAN26 scales had good internal consistency and were able to distinguish between subgroups of patients experiencing toxicity . Conclusions Although there is deterioration in HRQL following CRT , this resolves within 3 weeks . HRQL data support the use of capecitabine- over gemcitabine-based chemoradiation . The QLQ-PAN26 is a reliable and valid tool for use in patients receiving CRT Summary Background In the UK , chemotherapy is the st and ard treatment for inoperable , locally advanced , non-metastatic pancreatic cancer .  Chemoradiotherapy is also an acceptable treatment option , for which gemcitabine , fluorouracil , or capecitabine can be used as concurrent chemotherapy agents . We aim ed to assess the activity , safety , and feasibility of both gemcitabine-based and capecitabine-based chemoradiotherapy after induction chemotherapy for patients with locally advanced pancreatic cancer . Methods In this open-label , r and omised , two-arm , phase 2 trial , patients aged 18 years or older with histologically proven , locally advanced pancreatic cancer ( with a tumour diameter of 7 cm or less ) were recruited from 28 UK centres between Dec 24 , 2009 and Oct 25 , 2011 . After 12 weeks of induction gemcitabine and capecitabine chemotherapy ( three cycles of gemcitabine [ 1000 mg/m2 on days 1 , 8 , 15 of a 28-day cycle ] and capecitabine [ 830 mg/m2 twice daily on days 1–21 of a 28-day cycle ] ) , patients with stable or responding disease , tumour diameter of 6 cm or less , and WHO performance status 0–1 were r and omly assigned to receive a further cycle of gemcitabine and capecitabine chemotherapy followed by either gemcitabine ( 300 mg/m2 once per week ) or capecitabine ( 830 mg/m2 twice daily , Monday to Friday only ) , both in combination with radiation ( 50·4 Gy in 28 fractions ) . R and omisation ( 1:1 ) was done via a central computerised system and used stratified minimisation . The primary endpoint was 9-month progression-free survival , analysed by intention to treat including only those patients with valid CT assessment s. This trial is registered with IS RCT N , number 96169987 . Findings 114 patients were registered and 74 were r and omly allocated ( 38 to the gemcitabine group and 36 to the capecitabine group ) . After 9 months , 22 of 35 assessable patients ( 62·9 % , 80 % CI 50·6–73·9 ) in the capecitabine group and 18 of 35 assessable patients ( 51·4 % , 39·4–63·4 ) in the gemcitabine group had not progressed . Median overall survival was 15·2 months ( 95 % CI 13·9–19·2 ) in the capecitabine group and 13·4 months ( 95 % CI 11·0–15·7 ) in the gemcitabine group ( adjusted hazard ratio [ HR ] 0·39 , 95 % CI 0·18–0·81 ; p=0·012 ) . 12-month overall survival was 79·2 % ( 95 % CI 61·1–89·5 ) in the capecitabine group and 64·2 ( 95 % CI 46·4–77·5 ) in the gemcitabine group . Median progression-free survival was 12·0 months ( 95 % CI 10·2–14·6 ) in the capecitabine group and 10·4 months ( 95 % CI 8·9–12·5 ) in the gemcitabine group ( adjusted HR 0·60 , 95 % CI 0·32–1·12 ; p=0·11 ) . Eight patients in the capecitabine group had an objective response at 26 weeks , as did seven in the gemcitabine group . More patients in the gemcitabine group than in the capecitabine group had grade 3–4 haematological toxic effects ( seven [ 18 % ] vs none , p=0·008 ) and non-haematological toxic effects ( ten [ 26 % ] vs four [ 12 % ] , p=0·12 ) during chemoradiation treatment ; the most frequent events were leucopenia , neutropenia , and fatigue . Two patients in the capecitabine group progressed during the fourth cycle of induction chemotherapy . Of the 34 patients in the capecitabine group who received chemoradiotherapy , 25 ( 74 % ) received the full protocol dose of radiotherapy , compared with 26 ( 68 % ) of 38 patients in the gemcitabine group . Quality -of-life scores were not significantly different between the treatment groups . Interpretation Our results suggest that a capecitabine-based regimen might be preferable to a gemcitabine-based regimen in the context of consolidation chemoradiotherapy after a course of induction chemotherapy for locally advanced pancreatic cancer . However , these findings should be interpreted with caution because the difference in the primary endpoint was non-significant and the number of patients in the trial was small . Funding Cancer Research UK PURPOSE This phase II trial was design ed to assess the efficacy and safety of cetuximab , gemcitabine , and oxaliplatin followed by cetuximab , capecitabine , and radiation therapy in locally advanced pancreatic cancer ( LAPC ) . PATIENTS AND METHODS Treatment-naive eligible patients ( n = 69 ) received intravenous gemcitabine ( 1,000 mg/m(2 ) ) and oxaliplatin ( 100 mg/m(2 ) ) every 2 weeks for four doses , followed by radiation ( 50.4 Gy to the gross tumor only ) with concurrent capecitabine ( 825 mg/m(2 ) twice daily on radiation treatment days ) . Cetuximab ( 500 mg/m(2 ) ) was started on day 1 of chemotherapy and was continued every 2 weeks during chemotherapy and chemoradiotherapy . Diagnostic cytology specimens were immunostained for Smad4(Dpc4 ) expression . RESULTS Median overall survival time was 19.2 months ( 95 % CI , 14.2 to 24.2 months ) , and 1- 
    Output:
    
agent
Initial systemic chemotherapy ( 6 months ) with a combination regimen is recommended for most patients ( for some patients radiation therapy may be offered up front ) with Eastern Cooperative Oncology Group performance status 0 or 1 and a favorable comorbidity profile .
There is no clear evidence to support one regimen over another .
***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 This Phase II trial evaluated the toxicity , local control , and overall survival in patients treated with sequential gemcitabine and linear accelerator-based single-fraction stereotactic body radiotherapy ( SBRT ) .  METHODS AND MATERIAL S Twenty patients with locally advanced , nonmetastatic pancreatic adenocarcinoma were enrolled on this prospect i ve single-institution , institutional review board-approved study . Gemcitabine was administered on Days 1 , 8 , and 15 , and SBRT on Day 29 . Gemcitabine was restarted on Day 43 and continued for 3 - 5 cycles . SBRT of 25 Gy in a single fraction was delivered to the internal target volume with a 2- 3-mm margin using a nine-field intensity-modulated radiotherapy technique . Respiratory gating was used to account for breathing motion . Follow-up evaluations occurred at 4 - 6 weeks , 10 - 12 weeks , and every 3 months after SBRT . RESULTS All patients completed SBRT and a median of five cycles of chemotherapy . Follow-up for the 2 remaining alive patients was 25.1 and 36.4 months . No acute Grade 3 or greater nonhematologic toxicity was observed . Late Grade 3 or greater toxicities occurred in 1 patient ( 5 % ) and consisted of a duodenal perforation ( G4 ) . Three patients ( 15 % ) developed ulcers ( G2 ) that were medically managed . Overall , median survival was 11.8 months , with 1-year survival of 50 % and 2-year survival of 20 % . Using serial computed tomography , the freedom from local progression was 94 % at 1 year . CONCLUSION Linear accelerator-delivered SBRT with sequential gemcitabine result ed in excellent local control of locally advanced pancreatic cancer . Future studies will address strategies for reducing long-term duodenal toxicity associated with SBRT PURPOSE This phase III trial compared the efficacy and safety of gemcitabine ( Gem ) plus capecitabine ( GemCap ) versus single-agent Gem in advanced/metastatic pancreatic cancer . PATIENTS AND METHODS Patients were r and omly assigned to receive GemCap ( oral capecitabine 650 mg/m2 twice daily on days 1 to 14 plus Gem 1,000 mg/m2 by 30-minute infusion on days 1 and 8 every 3 weeks ) or Gem ( 1,000 mg/m2 by 30-minute infusion weekly for 7 weeks , followed by a 1-week break , and then weekly for 3 weeks every 4 weeks ) . Patients were stratified according to center , Karnofsky performance score ( KPS ) , presence of pain , and disease extent . RESULTS A total of 319 patients were enrolled between June 2001 and June 2004 .  Median overall survival ( OS ) time , the primary end point , was 8.4 and 7.2 months in the GemCap and Gem arms , respectively ( P = .234 ) . Post hoc analysis in patients with good KPS ( score of 90 to 100 ) showed a significant prolongation of median OS time in the GemCap arm compared with the Gem arm ( 10.1 v 7.4 months , respectively ; P = .014 ) . The overall frequency of grade 3 or 4 adverse events was similar in each arm . Neutropenia was the most frequent grade 3 or 4 adverse event in both arms . CONCLUSION GemCap failed to improve OS at a statistically significant level compared with st and ard Gem treatment . The safety of GemCap and Gem was similar . In the subgroup of patients with good performance status , median OS was improved significantly . GemCap is a practical regimen that may be considered as an alternative to single-agent Gem for the treatment of advanced/metastatic pancreatic cancer patients with a good performance status CONTEXT Sympathectomy is currently used as the fourth step of the modified World Health Organization ( WHO ) analgesic ladder . Sympathectomy can be performed early , before the second step on the ladder . OBJECTIVES We hypothesized that early sympathectomy would reduce pain and opioid consumption and improve quality of life . METHODS One hundred nine patients , with inoperable abdominal or pelvic cancer , reporting visceral pain of 40 - 70 on a visual analogue scale and taking nonopioid analgesics  were allocated r and omly into two groups : either blocks were performed before Step 2 of the WHO ladder , then analgesics were managed according to the ladder ( Group I ) or analgesics were given according to the WHO ladder , and blocks were performed as the fourth step after failure of strong opioids to control pain ( Group II ) . Visual analogue scale scores , responder analysis , daily opioid consumption , related side effects , and quality of life were assessed . RESULTS Responders were significantly higher in Group I ( P < 0.0001 ) , and partial responders and nonresponders significantly increased in Group II ( P < 0.0001 and 0.006 , respectively ) . Opioid consumption significantly decreased in Group I ( P < 0.0001 during first 12 months and 0.007 at the last assessment time ) , with concomitant significant reduction in related side effects . The number of patients who had a good analgesic response on tramadol significantly increased in Group I during the first five months ( P < 0.05 ) . European Organization for Research and Treatment of Cancer Quality of Life Question naire-Core 30 global quality -of-life subscale scores revealed significant improvement until the fifth month in Group I ( P < 0.05 ) . CONCLUSION Sympathectomy before Step 2 on the WHO analgesic ladder seems to lead to better pain control , less opioid consumption , and better quality of life in cancer patients Purpose Chemoradiation therapy ( CRT ) for patients with locally advanced pancreatic cancer ( LAPC ) provides survival benefits but may result in considerable toxicity . Health-related quality of life ( HRQL ) measurements during CRT have not been widely reported . This paper reports HRQL data from the Selective Chemoradiation in Advanced Localised Pancreatic Cancer ( SCALOP ) trial , including validation of the QLQ-PAN26 tool in CRT . Methods and Material s Patients with locally advanced , inoperable , nonmetastatic carcinoma of the pancreas were eligible . Following 12 weeks of induction gemcitabine plus capecitabine ( GEMCAP ) chemotherapy , patients with stable and responding disease were r and omized to a further cycle of GEMCAP followed by capecitabine- or gemcitabine-based CRT .  HRQL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-C30 ) and the EORTC Pancreatic Cancer module ( PAN26 ) . Results A total of 114 patients from 28 UK centers were registered and 74 patients r and omized . There was improvement in the majority of HRQL scales during induction chemotherapy . Patients with significant deterioration in fatigue , appetite loss , and gastrointestinal symptoms during CRT recovered within 3 weeks following CRT . Differences in changes in HRQL scores between trial arms rarely reached statistical significance ; however , where they did , they favored capecitabine therapy . PAN26 scales had good internal consistency and were able to distinguish between subgroups of patients experiencing toxicity . Conclusions Although there is deterioration in HRQL following CRT , this resolves within 3 weeks . HRQL data support the use of capecitabine- over gemcitabine-based chemoradiation . The QLQ-PAN26 is a reliable and valid tool for use in patients receiving CRT Summary Background In the UK , chemotherapy is the st and ard treatment for inoperable , locally advanced , non-metastatic pancreatic cancer .  Chemoradiotherapy is also an acceptable treatment option , for which gemcitabine , fluorouracil , or capecitabine can be used as concurrent chemotherapy agents . We aim ed to assess the activity , safety , and feasibility of both gemcitabine-based and capecitabine-based chemoradiotherapy after induction chemotherapy for patients with locally advanced pancreatic cancer . Methods In this open-label , r and omised , two-arm , phase 2 trial , patients aged 18 years or older with histologically proven , locally advanced pancreatic cancer ( with a tumour diameter of 7 cm or less ) were recruited from 28 UK centres between Dec 24 , 2009 and Oct 25 , 2011 . After 12 weeks of induction gemcitabine and capecitabine chemotherapy ( three cycles of gemcitabine [ 1000 mg/m2 on days 1 , 8 , 15 of a 28-day cycle ] and capecitabine [ 830 mg/m2 twice daily on days 1–21 of a 28-day cycle ] ) , patients with stable or responding disease , tumour diameter of 6 cm or less , and WHO performance status 0–1 were r and omly assigned to receive a further cycle of gemcitabine and capecitabine chemotherapy followed by either gemcitabine ( 300 mg/m2 once per week ) or capecitabine ( 830 mg/m2 twice daily , Monday to Friday only ) , both in combination with radiation ( 50·4 Gy in 28 fractions ) . R and omisation ( 1:1 ) was done via a central computerised system and used stratified minimisation . The primary endpoint was 9-month progression-free survival , analysed by intention to treat including only those patients with valid CT assessment s. This trial is registered with IS RCT N , number 96169987 . Findings 114 patients were registered and 74 were r and omly allocated ( 38 to the gemcitabine group and 36 to the capecitabine group ) . After 9 months , 22 of 35 assessable patients ( 62·9 % , 80 % CI 50·6–73·9 ) in the capecitabine group and 18 of 35 assessable patients ( 51·4 % , 39·4–63·4 ) in the gemcitabine group had not progressed . Median overall survival was 15·2 months ( 95 % CI 13·9–19·2 ) in the capecitabine group and 13·4 months ( 95 % CI 11·0–15·7 ) in the gemcitabine group ( adjusted hazard ratio [ HR ] 0·39 , 95 % CI 0·18–0·81 ; p=0·012 ) . 12-month overall survival was 79·2 % ( 95 % CI 61·1–89·5 ) in the capecitabine group and 64·2 ( 95 % CI 46·4–77·5 ) in the gemcitabine group . Median progression-free survival was 12·0 months ( 95 % CI 10·2–14·6 ) in the capecitabine group and 10·4 months ( 95 % CI 8·9–12·5 ) in the gemcitabine group ( adjusted HR 0·60 , 95 % CI 0·32–1·12 ; p=0·11 ) . Eight patients in the capecitabine group had an objective response at 26 weeks , as did seven in the gemcitabine group . More patients in the gemcitabine group than in the capecitabine group had grade 3–4 haematological toxic effects ( seven [ 18 % ] vs none , p=0·008 ) and non-haematological toxic effects ( ten [ 26 % ] vs four [ 12 % ] , p=0·12 ) during chemoradiation treatment ; the most frequent events were leucopenia , neutropenia , and fatigue . Two patients in the capecitabine group progressed during the fourth cycle of induction chemotherapy . Of the 34 patients in the capecitabine group who received chemoradiotherapy , 25 ( 74 % ) received the full protocol dose of radiotherapy , compared with 26 ( 68 % ) of 38 patients in the gemcitabine group . Quality -of-life scores were not significantly different between the treatment groups . Interpretation Our results suggest that a capecitabine-based regimen might be preferable to a gemcitabine-based regimen in the context of consolidation chemoradiotherapy after a course of induction chemotherapy for locally advanced pancreatic cancer . However , these findings should be interpreted with caution because the difference in the primary endpoint was non-significant and the number of patients in the trial was small . Funding Cancer Research UK PURPOSE This phase II trial was design ed to assess the efficacy and safety of cetuximab , gemcitabine , and oxaliplatin followed by cetuximab , capecitabine , and radiation therapy in locally advanced pancreatic cancer ( LAPC ) . PATIENTS AND METHODS Treatment-naive eligible patients ( n = 69 ) received intravenous gemcitabine ( 1,000 mg/m(2 ) ) and oxaliplatin ( 100 mg/m(2 ) ) every 2 weeks for four doses , followed by radiation ( 50.4 Gy to the gross tumor only ) with concurrent capecitabine ( 825 mg/m(2 ) twice daily on radiation treatment days ) . Cetuximab ( 500 mg/m(2 ) ) was started on day 1 of chemotherapy and was continued every 2 weeks during chemotherapy and chemoradiotherapy . Diagnostic cytology specimens were immunostained for Smad4(Dpc4 ) expression . RESULTS Median overall survival time was 19.2 months ( 95 % CI , 14.2 to 24.2 months ) , and 1- 
    Output:
    