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: Background : Since 1989 we have enrolled patients with clinical -radiological stage III-IVA thymomas , independent of the surgeon 's judgment of resectability , into a prospect i ve study of neoadjuvant chemotherapy – surgery and postoperative radiotherapy . In this article , we review our long-term experience of neoadjuvant chemotherapy of advanced stage ( III-IVA ) thymomas . Methods : From 1989 to 2004 , 30 patients with Masaoka stage III and IVA thymomas underwent neoadjuvant chemotherapy , surgery , and postoperative radiotherapy . The neoadjuvant and adjuvant chemotherapy consisted of three courses of cisplatin , epidoxorubicin , and etoposide every 3 weeks . Adjuvant radiotherapy consisted of 45 Gy for complete resections or 60 Gy for incomplete resections . Results : The preoperative diagnosis of invasive thymomas was obtained for 16 patients : five by mediastinotomy , seven by video-assisted thoracic surgery , and four by fine needle aspiration . For 14 patients , no histological diagnosis was available , but a thymus-related syndrome was present in all . Twenty-seven patients are still alive ( 25 disease-free ) and three have died ( one disease-free ) . The 10-year survival rates were 85.7 % and 76.1 % for stage III and IVA thymomas , respectively ( difference not significant ) . Only the World Health Organization pathological diagnosis significantly affected the survival , with type B3 having a worse prognosis than type AB , B1 , and B2 thymomas ( p = 0.02 ) . Conclusion : The multimodality treatment of stage III and IVA thymomas by means of neoadjuvant chemotherapy provides good long-term outcomes in both stages of the disease PURPOSE To evaluate tumor resectability after induction chemotherapy and to determine disease-free and overall survival rates of patients with locally advanced unresectable thymoma that received a multimodal treatment regimen . PATIENTS AND METHODS Twenty-two patients ( 9 men , 13 women ) with histologically confirmed invasive thymoma were treated with a multidisciplinary regimen consisting of three courses of induction chemotherapy , surgical resection , and radiation therapy , followed by three courses of consolidation chemotherapy .  The median age was 47 years ( range , 25 - 70 ) . Eleven patients had stage III disease , 10 patients , stage IVA , and one patient , IVB . The most common histologic type was lymphocytic . Induction chemotherapy consisted of 500 mg/m(2 ) of cyclophosphamide on day 1 ; doxorubicin ( 20 mg/m(2 ) per day ) on days 1 - 3 via continuous infusion ( a total of 60 mg/m(2 ) ) ; cisplatin ( 30 mg/m(2 ) per day ) on days 1 - 3 ( a total of 90 mg/m(2 ) ) ; and prednisone ( 100 mg per day ) on days 1 - 5 . This cycle was repeated three times at 3 - 4-week intervals . Patients then underwent surgery for tumor resection and received radiotherapy . Consolidation chemotherapy given at 80 % of the induction chemotherapy doses of cyclophosphamide , doxorubicin , and cisplatin and 100 % of the dose of prednisone was then repeated every 3 - 4 weeks for a total of three courses . RESULTS Induction chemotherapy produced major responses in 17 ( 77 % ) of the 22 patients including 3 ( 14 % ) complete responses ( CR ) and 14 ( 63 % ) partial responses ( PR ) . Twenty-one patients underwent surgical exploration : 16 ( 76 % ) had complete resection and 5 ( 24 % ) had incomplete resection ; one patient refused surgery . All 22 patients received radiation therapy . Nineteen of 22 patients completed the planned therapy , and all but one had completed consolidation chemotherapy at the time of analysis . With a median follow-up time of 50.3 months , 18 of the 19 patients who completed the multidisciplinary approach were disease-free . Of the 22 patients originally registered , 20 were alive at the time of analysis ( one patient died of endocarditis , and one died of recurrent disease ) . The overall survival rate was 95 % at 5 years ( 95 % confidence interval ( CI ) , 0.87 - 1.0 ) and 79 % at 7 years ( 95 % CI , 0.55 - 1.0 ) . The progression-free survival rates were 77 % at 5 years ( 95 % CI , 0.58 - 1.0 ) and 77 % at 7 years ( 95 % CI , 0.58 - 1.0 ) . The major side effect from induction and consolidation chemotherapy was myelosuppression . Nine patients experienced grade III/IV neutropenia , which included neutropenic fever in two patients , and grade III thrombocytopenia in two patients . The most common nonhematologic side effects were fatigue , nausea and vomiting , and decreased appetite . One patient experienced acute respiratory distress syndrome after surgical resection and required a prolonged hospitalization . No patients developed cardiac toxic effects , and no surgical mortality occurred . CONCLUSIONS The use of induction chemotherapy to optimize surgical resectability of thymoma followed by radiation therapy and consolidation chemotherapy lead to good control of residual disease and high overall survival rates . We believe that this combined multidisciplinary approach prolongs lives and may cure locally advanced unresectable malignant thymomas . Future prospect i ve multi-institutional studies are needed to further verify or define the best treatment for this patient population From 1990 to 1997 , 16 consecutive patients with stage III and IVa invasive thymoma were treated in a single institution with primary chemotherapy consisting in adriamycin ( 40 mg m–2 ) , cisplatin ( 50 mg m–2 ) administered intravenously on day 1 , vincristine ( 0.6 mg m–2 ) on day 2 and cyclophosphamide ( 700 mg m–2 ) on day 4 ( ADOC ) . The courses were repeated every 3 weeks . The aim was to evaluate the impact of this cytotoxic regimen with respect to response rate , per cent of patients radically resected , time to progression and overall survival . Two complete responses ( one clinical and one pathological ) and 11 partial responses were observed ( overall response rate 81.2 % ) ; two patients had stable disease and one progressed . Toxicity was mild as only two patients developed grade III/IV neutropenia and one patient grade III nausea/vomiting . Nine patients were radically resected ( five out of ten with stage III , and four out of six with stage IVa ) . Median time to progression and overall survival was 33.2 and 47.5 months respectively . Three patients were alive and disease free after more than 5 years . The ADOC scheme is highly active and manageable in the treatment of locally advanced thymoma . As a preoperative approach it should be offered to patients not amenable to surgery or to those surgically resectable but with a great deal of morbidity From 1977 to 1990 , 37 patients with Stage III or IV invasive thymoma ( 20 men and 17 women ; median age , 40 years of age ) were referred for chemotherapy to the Padova Medical Oncology Department . All patients initially received the same regimen ( 50 mg/m2 of cisplatin and 40 mg/m2 of doxorubicin intravenously ( IV ) on day 1 , 0.6 mg/m2 of vincristine IV on day 3 , and 700 mg/m2 of cyclophosphamide IV on day 4 [ ADOC ] ) , recycling at monthly intervals . No life‐threatening side effects were noted . The overall clinical response rate ( complete response plus partial response ) was 91.8 % , with 43 % complete remissions . Median duration of response and survival were 12 months ( range , 2 to 96 + months ) and 15 months ( range , 5 to 96 + months ) , respectively . Seven of the 16 complete remissions were pathologically confirmed at subsequent thoracotomy . Other chemotherapy combinations and radiation therapy have been applied as second‐line treatment , achieving only minimal responses . In the opinion of the authors , such chemotherapy deserves evaluation for adjuvant and neo‐adjuvant treatment of invasive ( and /or inoperable ) thymoma due to the high complete response rate and overall response rate Thymic malignancies are rare epithelial tumors that may be aggressive and difficult to treat.1 Thymomas are usually localized to the anterior mediastinum and are frequently eligible for upfront surgical resection , which is the mainstay of the curative-intent treatment.1 However , approximately 30 % of patients present with an advanced tumor at the time of diagnosis , with invasion of neighboring organs , dissemination to the pleura , the pericardium , or less frequently extrathoracic organs . In such cases , chemotherapy has been used both to reduce the tumor burden — possibly allowing subsequent surgery or radiotherapy— and to achieve prolonged disease control . Recurrence after resection may be similarly treated with chemotherapy .  Thymic carcinomas , although rare , are usually already advanced at the time of presentation , and systemic therapy is important for almost all of these patients . Knowledge regarding chemotherapy for thymic tumors has mainly been based on retrospective series,2–9 although several prospect i ve trials have also been conducted.10–21 These studies have clearly demonstrated the chemosensitivity of thymoma , and to a lesser extent thymic carcinoma , to various cytotoxic agents and combinations . However , details of patient selection are often lacking ( either disease extent or general condition ) , and the intent of the treatment sequence is often vague . Adoption of a common language and definition of terms is crucial for the International Thymic Malignancies Interest Group ( ITMIG ) effort to develop a international prospect i ve data base of thymic tumors . The article by Huang et al.22 provides definitions for survival and endpoints for recurrences assessment and discusses how to measure response to treatment . Herein , we discuss additional points with regard to chemotherapy , including treatment sequence , general modalities , and impact of corticosteroids Background : To evaluate the safety and efficacy of dose-dense weekly chemotherapy in the treatment of advanced thymoma . Methods : Subjects comprised patients with histologically documented chemotherapy-naïve thymoma with stage-IVa or IVb disease . Thymic carcinoma , carcinoid or lymphoma cases were excluded . Patients received 9 weeks of chemotherapy : cisplatin ( 25 mg m−2 ) on weeks 1–9 ; vincristine ( 1 mg m−2 ) on weeks 1 , 2 , 4 , 6 and 8 ; and doxorubicin ( 40 mg m−2 ) and etoposide ( 80 mg m−2 ) on days 1–3 of weeks 1 , 3 , 5 , 7 and 9 . Chemotherapy courses were supported by granulocyte colony-stimulating factor . Post- protocol local therapy was allowed . Results : From July 1997 to March 2004 , 30 patients were entered . Three were ineligible due to different histology . Chemotherapy-associated toxicity was mainly haematological and was well tolerated , with no deaths due to toxicity , and 87 % of patients completed the planned 9-week regimen . Overall response rate was 59 % , with 16 of the 27 eligible patients achieving partial response . Median progression-fee survival ( PFS ) was 0.79 years ( 95 % confidence interval : 0.52–1.40 years ) , and PFS at 1 and 2 years was 37 and 15 % , respectively . Overall survival rates at 2 and 5 years were 89 and 65 % , respectively . Conclusion : In stage-IV thymoma patients , weekly dose-dense chemotherapy offers similar activity to conventional regimens BACKGROUND To compare the efficacy and toxicity of three platinum-based combination regimens against cisplatin plus irinotecan ( IP ) in patients with untreated advanced non-small-cell lung cancer ( NSCLC ) by a non-inferiority design . PATIENTS AND METHODS A total of 602 patients were r and omly assigned to one of four regimens : cisplatin 80 mg/m(2 ) on day 1 plus irinotecan 60 mg/m(2 ) on days 1 , 8 , 15 every 4 weeks ( IP ) carboplatin AUC 6.0 min x mg/mL ( area under the concentration-time curve ) on day 1 plus paclitaxel 200 mg/m(2 ) on day 1 every 3 weeks ( TC ) ; cisplatin 80 mg/m(2 ) on day 1 plus gemcitabine 1000 mg/m(2 ) on days 1 , 8 every 3 weeks ( GP ) ; and cisplatin 80 mg/m(2 ) on day 1 plus vinorelbine 25 mg/m(2 ) on days 1 , 8 every 3 weeks ( NP ) . RESULTS The response rate , median survival time , and 1-year survival rate were 31.0 % , 13.9 months , 59.2 % , respectively , in IP ; 32.4 % , 12.3 months , 51.0 % in TC ; 30.1 % , 14.0 months , 59 
    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: Background : Since 1989 we have enrolled patients with clinical -radiological stage III-IVA thymomas , independent of the surgeon 's judgment of resectability , into a prospect i ve study of neoadjuvant chemotherapy – surgery and postoperative radiotherapy . In this article , we review our long-term experience of neoadjuvant chemotherapy of advanced stage ( III-IVA ) thymomas . Methods : From 1989 to 2004 , 30 patients with Masaoka stage III and IVA thymomas underwent neoadjuvant chemotherapy , surgery , and postoperative radiotherapy . The neoadjuvant and adjuvant chemotherapy consisted of three courses of cisplatin , epidoxorubicin , and etoposide every 3 weeks . Adjuvant radiotherapy consisted of 45 Gy for complete resections or 60 Gy for incomplete resections . Results : The preoperative diagnosis of invasive thymomas was obtained for 16 patients : five by mediastinotomy , seven by video-assisted thoracic surgery , and four by fine needle aspiration . For 14 patients , no histological diagnosis was available , but a thymus-related syndrome was present in all . Twenty-seven patients are still alive ( 25 disease-free ) and three have died ( one disease-free ) . The 10-year survival rates were 85.7 % and 76.1 % for stage III and IVA thymomas , respectively ( difference not significant ) . Only the World Health Organization pathological diagnosis significantly affected the survival , with type B3 having a worse prognosis than type AB , B1 , and B2 thymomas ( p = 0.02 ) . Conclusion : The multimodality treatment of stage III and IVA thymomas by means of neoadjuvant chemotherapy provides good long-term outcomes in both stages of the disease PURPOSE To evaluate tumor resectability after induction chemotherapy and to determine disease-free and overall survival rates of patients with locally advanced unresectable thymoma that received a multimodal treatment regimen . PATIENTS AND METHODS Twenty-two patients ( 9 men , 13 women ) with histologically confirmed invasive thymoma were treated with a multidisciplinary regimen consisting of three courses of induction chemotherapy , surgical resection , and radiation therapy , followed by three courses of consolidation chemotherapy .  The median age was 47 years ( range , 25 - 70 ) . Eleven patients had stage III disease , 10 patients , stage IVA , and one patient , IVB . The most common histologic type was lymphocytic . Induction chemotherapy consisted of 500 mg/m(2 ) of cyclophosphamide on day 1 ; doxorubicin ( 20 mg/m(2 ) per day ) on days 1 - 3 via continuous infusion ( a total of 60 mg/m(2 ) ) ; cisplatin ( 30 mg/m(2 ) per day ) on days 1 - 3 ( a total of 90 mg/m(2 ) ) ; and prednisone ( 100 mg per day ) on days 1 - 5 . This cycle was repeated three times at 3 - 4-week intervals . Patients then underwent surgery for tumor resection and received radiotherapy . Consolidation chemotherapy given at 80 % of the induction chemotherapy doses of cyclophosphamide , doxorubicin , and cisplatin and 100 % of the dose of prednisone was then repeated every 3 - 4 weeks for a total of three courses . RESULTS Induction chemotherapy produced major responses in 17 ( 77 % ) of the 22 patients including 3 ( 14 % ) complete responses ( CR ) and 14 ( 63 % ) partial responses ( PR ) . Twenty-one patients underwent surgical exploration : 16 ( 76 % ) had complete resection and 5 ( 24 % ) had incomplete resection ; one patient refused surgery . All 22 patients received radiation therapy . Nineteen of 22 patients completed the planned therapy , and all but one had completed consolidation chemotherapy at the time of analysis . With a median follow-up time of 50.3 months , 18 of the 19 patients who completed the multidisciplinary approach were disease-free . Of the 22 patients originally registered , 20 were alive at the time of analysis ( one patient died of endocarditis , and one died of recurrent disease ) . The overall survival rate was 95 % at 5 years ( 95 % confidence interval ( CI ) , 0.87 - 1.0 ) and 79 % at 7 years ( 95 % CI , 0.55 - 1.0 ) . The progression-free survival rates were 77 % at 5 years ( 95 % CI , 0.58 - 1.0 ) and 77 % at 7 years ( 95 % CI , 0.58 - 1.0 ) . The major side effect from induction and consolidation chemotherapy was myelosuppression . Nine patients experienced grade III/IV neutropenia , which included neutropenic fever in two patients , and grade III thrombocytopenia in two patients . The most common nonhematologic side effects were fatigue , nausea and vomiting , and decreased appetite . One patient experienced acute respiratory distress syndrome after surgical resection and required a prolonged hospitalization . No patients developed cardiac toxic effects , and no surgical mortality occurred . CONCLUSIONS The use of induction chemotherapy to optimize surgical resectability of thymoma followed by radiation therapy and consolidation chemotherapy lead to good control of residual disease and high overall survival rates . We believe that this combined multidisciplinary approach prolongs lives and may cure locally advanced unresectable malignant thymomas . Future prospect i ve multi-institutional studies are needed to further verify or define the best treatment for this patient population From 1990 to 1997 , 16 consecutive patients with stage III and IVa invasive thymoma were treated in a single institution with primary chemotherapy consisting in adriamycin ( 40 mg m–2 ) , cisplatin ( 50 mg m–2 ) administered intravenously on day 1 , vincristine ( 0.6 mg m–2 ) on day 2 and cyclophosphamide ( 700 mg m–2 ) on day 4 ( ADOC ) . The courses were repeated every 3 weeks . The aim was to evaluate the impact of this cytotoxic regimen with respect to response rate , per cent of patients radically resected , time to progression and overall survival . Two complete responses ( one clinical and one pathological ) and 11 partial responses were observed ( overall response rate 81.2 % ) ; two patients had stable disease and one progressed . Toxicity was mild as only two patients developed grade III/IV neutropenia and one patient grade III nausea/vomiting . Nine patients were radically resected ( five out of ten with stage III , and four out of six with stage IVa ) . Median time to progression and overall survival was 33.2 and 47.5 months respectively . Three patients were alive and disease free after more than 5 years . The ADOC scheme is highly active and manageable in the treatment of locally advanced thymoma . As a preoperative approach it should be offered to patients not amenable to surgery or to those surgically resectable but with a great deal of morbidity From 1977 to 1990 , 37 patients with Stage III or IV invasive thymoma ( 20 men and 17 women ; median age , 40 years of age ) were referred for chemotherapy to the Padova Medical Oncology Department . All patients initially received the same regimen ( 50 mg/m2 of cisplatin and 40 mg/m2 of doxorubicin intravenously ( IV ) on day 1 , 0.6 mg/m2 of vincristine IV on day 3 , and 700 mg/m2 of cyclophosphamide IV on day 4 [ ADOC ] ) , recycling at monthly intervals . No life‐threatening side effects were noted . The overall clinical response rate ( complete response plus partial response ) was 91.8 % , with 43 % complete remissions . Median duration of response and survival were 12 months ( range , 2 to 96 + months ) and 15 months ( range , 5 to 96 + months ) , respectively . Seven of the 16 complete remissions were pathologically confirmed at subsequent thoracotomy . Other chemotherapy combinations and radiation therapy have been applied as second‐line treatment , achieving only minimal responses . In the opinion of the authors , such chemotherapy deserves evaluation for adjuvant and neo‐adjuvant treatment of invasive ( and /or inoperable ) thymoma due to the high complete response rate and overall response rate Thymic malignancies are rare epithelial tumors that may be aggressive and difficult to treat.1 Thymomas are usually localized to the anterior mediastinum and are frequently eligible for upfront surgical resection , which is the mainstay of the curative-intent treatment.1 However , approximately 30 % of patients present with an advanced tumor at the time of diagnosis , with invasion of neighboring organs , dissemination to the pleura , the pericardium , or less frequently extrathoracic organs . In such cases , chemotherapy has been used both to reduce the tumor burden — possibly allowing subsequent surgery or radiotherapy— and to achieve prolonged disease control . Recurrence after resection may be similarly treated with chemotherapy .  Thymic carcinomas , although rare , are usually already advanced at the time of presentation , and systemic therapy is important for almost all of these patients . Knowledge regarding chemotherapy for thymic tumors has mainly been based on retrospective series,2–9 although several prospect i ve trials have also been conducted.10–21 These studies have clearly demonstrated the chemosensitivity of thymoma , and to a lesser extent thymic carcinoma , to various cytotoxic agents and combinations . However , details of patient selection are often lacking ( either disease extent or general condition ) , and the intent of the treatment sequence is often vague . Adoption of a common language and definition of terms is crucial for the International Thymic Malignancies Interest Group ( ITMIG ) effort to develop a international prospect i ve data base of thymic tumors . The article by Huang et al.22 provides definitions for survival and endpoints for recurrences assessment and discusses how to measure response to treatment . Herein , we discuss additional points with regard to chemotherapy , including treatment sequence , general modalities , and impact of corticosteroids Background : To evaluate the safety and efficacy of dose-dense weekly chemotherapy in the treatment of advanced thymoma . Methods : Subjects comprised patients with histologically documented chemotherapy-naïve thymoma with stage-IVa or IVb disease . Thymic carcinoma , carcinoid or lymphoma cases were excluded . Patients received 9 weeks of chemotherapy : cisplatin ( 25 mg m−2 ) on weeks 1–9 ; vincristine ( 1 mg m−2 ) on weeks 1 , 2 , 4 , 6 and 8 ; and doxorubicin ( 40 mg m−2 ) and etoposide ( 80 mg m−2 ) on days 1–3 of weeks 1 , 3 , 5 , 7 and 9 . Chemotherapy courses were supported by granulocyte colony-stimulating factor . Post- protocol local therapy was allowed . Results : From July 1997 to March 2004 , 30 patients were entered . Three were ineligible due to different histology . Chemotherapy-associated toxicity was mainly haematological and was well tolerated , with no deaths due to toxicity , and 87 % of patients completed the planned 9-week regimen . Overall response rate was 59 % , with 16 of the 27 eligible patients achieving partial response . Median progression-fee survival ( PFS ) was 0.79 years ( 95 % confidence interval : 0.52–1.40 years ) , and PFS at 1 and 2 years was 37 and 15 % , respectively . Overall survival rates at 2 and 5 years were 89 and 65 % , respectively . Conclusion : In stage-IV thymoma patients , weekly dose-dense chemotherapy offers similar activity to conventional regimens BACKGROUND To compare the efficacy and toxicity of three platinum-based combination regimens against cisplatin plus irinotecan ( IP ) in patients with untreated advanced non-small-cell lung cancer ( NSCLC ) by a non-inferiority design . PATIENTS AND METHODS A total of 602 patients were r and omly assigned to one of four regimens : cisplatin 80 mg/m(2 ) on day 1 plus irinotecan 60 mg/m(2 ) on days 1 , 8 , 15 every 4 weeks ( IP ) carboplatin AUC 6.0 min x mg/mL ( area under the concentration-time curve ) on day 1 plus paclitaxel 200 mg/m(2 ) on day 1 every 3 weeks ( TC ) ; cisplatin 80 mg/m(2 ) on day 1 plus gemcitabine 1000 mg/m(2 ) on days 1 , 8 every 3 weeks ( GP ) ; and cisplatin 80 mg/m(2 ) on day 1 plus vinorelbine 25 mg/m(2 ) on days 1 , 8 every 3 weeks ( NP ) . RESULTS The response rate , median survival time , and 1-year survival rate were 31.0 % , 13.9 months , 59.2 % , respectively , in IP ; 32.4 % , 12.3 months , 51.0 % in TC ; 30.1 % , 14.0 months , 59 
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