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: Imiquimod is an immune response modifier that acts through Toll-like receptor 7 to induce innate and cell-mediated immune responses . This ongoing phase III , open-label study conducted in Europe is evaluating the long-term ( 5 year ) clinical efficacy and safety of imiquimod 5 % cream applied once daily 5 times per week ( 5 x/week ) for 6 weeks for the treatment of superficial basal cell carcinoma ( sBCC ) . A total of 182 subjects were enrolled . The initial sBCC clearance rate was 90 % ( 12-week post treatment ) , whereas the proportion of subjects who were clinical ly clear at 2 years ( current time point ) was estimated to be 79.4 % . Local skin/application site reactions were the most frequently reported safety findings . Initial efficacy rates of imiquimod applied 5 x/week for 6 weeks demonstrate its clinical utility as an alternative approach to the treatment of sBCC . The recurrence rate seen to date supports ongoing follow up of subjects treated with imiquimod OBJECTIVE To compare 5-year lesion recurrence rates in primary nodular basal cell carcinoma treated with topical methyl aminolevulinate photodynamic therapy ( PDT ) or simple excision surgery . DESIGN Prospect i ve , r and omized , multicenter study . SETTING University hospital dermatology departments . PATIENTS A total of 97 patients , 50 with 53 lesions treated with methyl aminolevulinate PDT and 47 with 52 lesions treated by excision surgery  , were included in the per protocol analysis . Of the lesions treated with methyl aminolevulinate PDT and surgery , 49 and 52 , respectively , showed complete clinical response at 3 months after treatment and were observed for long-term outcome evaluation . INTERVENTIONS Topical methyl aminolevulinate cream , 160 mg/g , applied for 3 hours before illumination ( 75 J/cm(2 ) of red light at 570 to 670 nm ) on 2 or 4 occasions ( 12 [ 23 % ] of 53 lesions ) ; or excision surgery . MAIN OUTCOME MEASURES Histologically confirmed lesion recurrence , sustained lesion complete response rate ( time-to-event analysis ) , and investigator assessment of cosmetic outcome , 5 years after the last treatment . RESULTS At 5 years , recurrence was documented in 7 ( 14 % ) of 49 lesions ( 95 % confidence interval [ CI ] , 6%-27 % ) treated with methyl aminolevulinate PDT vs 2 ( 4 % ) of 52 lesions ( 95 % CI , 1%-13 % ) treated with excision surgery ( P = .09 ) . Estimated sustained lesion complete response rates were 76 % ( 95 % CI , 59%-87 % ) and 96 % ( 95 % CI , 84%-99 % ) , respectively ( P = .01 ) . More patients treated with methyl aminolevulinate PDT than surgery had an excellent or good cosmetic outcome : 27 ( 87 % ) of 31 patients ( 95 % CI , 70%-96 % ) vs 19 ( 54 % ) of 35 patients ( 95 % CI , 37%-71 % ) ( P = .007 ) . CONCLUSIONS Long-term follow-up indicates superior efficacy of surgery to methyl aminolevulinate PDT in nodular basal cell carcinoma . However , methyl aminolevulinate PDT is also an effective treatment for this indication and exhibits a more favorable cosmetic outcome In a clinical trial of 172 patients at four medical centers , interferon alfa-2b ( 1.5 x 10(6 ) IU ) or a placebo was injected directly into biopsy-proved noduloulcerative or superficial basal cell carcinomas three times weekly for 3 weeks , for a cumulative dose of 13.5 million IU . Efficacy of treatment was determined at 16 to 20 weeks by examination of biopsy specimens that demonstrated cure of lesions in 86 % of interferon-treated patients and in only 29 % of placebo-treated patients . During the treatment course and follow-up , an initial inflammatory response was observed at the treatment sites , followed by diminished erythema , improvement in overall appearance , and a decrease in size of lesions . Side effects of treatment , mainly flu-like symptoms , were usually mild and transient and occurred more commonly in the interferon-treated group . Only three patients , all in the interferon-treated group , discontinued therapy because of side effects . One year after initiation of therapy , 81 % of interferon recipients and 20 % of those given the placebo remained tumor free . Noduloulcerative and superficial lesions were equally responsive to treatment with interferon . For some patients with noduloulcerative or superficial basal cell carcinomas , intralesional interferon alfa-2b may be an alternative , effective treatment BACKGROUND Basal cell carcinomas ( BCCs ) are usually treated with ablative procedures . A nonsurgical treatment alternative would be of value in selected patients . OBJECTIVE We evaluated the safety and efficacy of a new preparation for intralesional sustained-release chemotherapy with MPI 5003 , 5-Fluorouracil Therapeutic Implant , for treatment of BCCs . METHODS Two doses of intralesional MPI 5003 ( 0.25 and 0.5 ml ) were compared in a double-blind study of 20 patients with biopsy-proven BCC . One BCC per patient was treated weekly for up to 6 weeks and followed up monthly for 3 months until excisional biopsy for histologic examination . Before excision the cosmetic appearance of the test site was grade d. RESULTS Eighty percent of 10 BCCs treated with 0.5 ml of MPI 5003 had histologically confirmed cures as compared with 60 % of 10 tumors treated with the lower dose ( 0.25 ml ) . Cosmetic assessment s before excision were typically good to excellent . No systemic side effects occurred . CONCLUSION Results indicate the potential of MPI 5003 for targeted local chemotherapy for BCC BACKGROUND Superficial basal-cell carcinoma is most commonly treated with topical non-surgical treatments , such as photodynamic therapy or topical creams . Photodynamic therapy is considered the preferable treatment , although this has not been previously tested in a r and omised control trial . We assessed the effectiveness of photodynamic therapy compared with imiquimod or fluorouracil in patients with superficial basal-cell carcinoma . METHODS In this single blind , non-inferiority , r and omised controlled multicentre trial , we enrolled patients with a histologically proven superficial basal-cell carcinoma at seven hospitals in the Netherl and s. Patients were r and omly assigned to receive treatment with methylaminolevulinate photodynamic therapy ( MAL-PDT ; two sessions with an interval of 1 week ) , imiquimod cream ( once daily , five times a week for 6 weeks ) , or fluorouracil cream ( twice daily for 4 weeks ) . Follow-up was at 3 and 12 months post-treatment . Data were collected by one observer who was blinded to the assigned treatment . The primary outcome was the proportion of patients free of tumour at both 3 and 12 month follow up . A pre-specified non-inferiority margin of 10 % was used and modified intention-to-treat analyses were done . This trial is registered as an International St and ard R and omised controlled trial ( IS RCT N 79701845 ) . FINDINGS 601 patients were r and omised : 202 to receive MAL-PDT , 198 to receive imiquimod , and 201 to receive fluorouracil .  A year after treatment , 52 of 196 patients treated with MAL-PDT , 31 of 189 treated with imiquimod , and 39 of 198 treated with fluorouracil had tumour residue or recurrence . The proportion of patients tumour-free at both 3 and 12 month follow-up was 72.8 % ( 95 % CI 66.8 - 79.4 ) for MAL-PDT , 83.4 % ( 78.2 - 88.9 ) for imiquimod cream , and 80.1 % ( 74.7 - 85.9 ) for fluorouracil cream . The difference between  imiquimod and  MAL-PDT was 10.6 % ( 95 % CI 1.5 - 19.5 ; p=0.021 ) and 7.3 % ( -1.9 to 16.5 ; p=0.120 ) between fluorouracil and MAL-PDT , and between fluorouracil and imiquimod was -3.3 % ( -11.6 to 5.0 ; p=0.435 . For patients treated with MAL-PDT , moderate to severe pain and burning sensation were reported most often during the actual MAL-PDT session . For other local adverse reactions , local skin redness was most often reported as moderate or severe in all treatment groups . Patients treated with creams more often reported moderate to severe local swelling , erosion , crust formation , and itching of the skin than patients treated with MAL-PDT . In the MAL-PDT group no serious adverse events were reported . One patient treated with imiquimod and two patients treated with fluorouracil developed a local wound infection and needed additional treatment in the outpatient setting . INTERPRETATION Topical fluorouracil was non-inferior and imiquimod was superior to MAL-PDT for treatment of superficial basal-cell carcinoma . On the basis of these findings , imiquimod can be considered the preferred treatment , but all aspects affecting treatment choice should be weighted to select the best treatment for patients . FUNDING Grant of the Netherl and s Organization for Scientific Research ZONMW ( 08 - 82310 - 98 - 08626 ) Combinational cryosurgery during daily imiquimod application ( ' immunocryosurgery ' ) efficiently cures invading  basal cell carcinoma ( BCC ) . Since timing of the cryosurgery is considered crucial for effectiveness , our aim was to compare efficacy of two different timing schemes of the combination of cryosurgery and topical imiquimod : Cryosurgery ( a ) 2 weeks after ( Arm I ) vs ( b ) prior to the initiation of a 5 week daily imiquimod course ( Arm II ) . 16 patients with 21 BCC were recruited in this prospect i ve , r and omized , open-label trial . 14 patients with 17 BCC were evaluated ( Arm I : 7 patients /10 tumors vs Arm II : 7 patients /7 tumors ) during scheduled interim analysis at 6 month follow-up ( two patients dropped out , one non-compliant and one lost to follow up ) . The trial was revoked because study Arm I ( ' immunocryosurgery ' ) was significantly superior to Arm II ( adjuvant imiquimod ) in achieving tumor clearance ( 10/10 vs 3/7 tumors ; p=0.0147 ) and by overall treatment efficacy ( 9/10 vs 2/7 relapse-free tumors ; p=0.0345 ) . The same overall efficacy persisted after at least 18 months follow-up for those patients with tumor clearance after the trial treatment . The timing of cryosurgery during imiquimod application substantially determines the efficacy of this combinational approach in the treatment of BCC BACKGROUND Data suggest that photodynamic therapy using topical methyl aminolevulinate ( MAL PDT ) may be a noninvasive alternative to excisional surgery for nodular basal cell carcinoma ( BCC ) . In the studies described here , we investigated the histologic response , tolerability , and cosmetic outcome with MAL PDT for primary nodular BCC ( < or= 5 mm in depth ) . METHODS Two multicenter , r and omized , double-blind studies with similar design and procedures were conducted . After surface debridement and minor tumor debulking , MAL cream 160 mg/g  ( 66 patients with 75 lesions )  or placebo cream ( 65 patients with 75 lesions ) was applied for 3 h , followed by illumination with broad-spectrum red light ( 75 J/cm(2 ) , 570 - 670 nm ) . This was repeated 7 days later . Lesions with a partial response ( > or= 50 % reduction in greatest diameter ) at 3 months were re-treated ( 21 % ) . Treatment sites were excised at 3 months ( clinical nonresponders ) or 6 months ( clinical responders ) after the last treatment . RESULTS Histologically verified lesion complete response rates were higher with MAL PDT than with placebo [ 73 % ( 55/75 ) vs. 27 % ( 20/75 ) ] . Treatment was most effective for facial lesions ( 89 % complete response ) . Cosmetic outcome was good or excellent in 98 % of evaluable , completely responding lesions treated with MAL PDT . CONCLUSION Although longer follow-up studies are required , these promising data indicate the potential of topical MAL PDT as a noninvasive treatment alternative for nodular BCC Photodynamic therapy ( PDT ) using topical porphyrin-precursors is a promising treatment for  superficial basal cell carcinoma ( sBCC ) , but it needs further optimization . The aim of this study was to compare 5-year lesion ( 
    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: Imiquimod is an immune response modifier that acts through Toll-like receptor 7 to induce innate and cell-mediated immune responses . This ongoing phase III , open-label study conducted in Europe is evaluating the long-term ( 5 year ) clinical efficacy and safety of imiquimod 5 % cream applied once daily 5 times per week ( 5 x/week ) for 6 weeks for the treatment of superficial basal cell carcinoma ( sBCC ) . A total of 182 subjects were enrolled . The initial sBCC clearance rate was 90 % ( 12-week post treatment ) , whereas the proportion of subjects who were clinical ly clear at 2 years ( current time point ) was estimated to be 79.4 % . Local skin/application site reactions were the most frequently reported safety findings . Initial efficacy rates of imiquimod applied 5 x/week for 6 weeks demonstrate its clinical utility as an alternative approach to the treatment of sBCC . The recurrence rate seen to date supports ongoing follow up of subjects treated with imiquimod OBJECTIVE To compare 5-year lesion recurrence rates in primary nodular basal cell carcinoma treated with topical methyl aminolevulinate photodynamic therapy ( PDT ) or simple excision surgery . DESIGN Prospect i ve , r and omized , multicenter study . SETTING University hospital dermatology departments . PATIENTS A total of 97 patients , 50 with 53 lesions treated with methyl aminolevulinate PDT and 47 with 52 lesions treated by excision surgery  , were included in the per protocol analysis . Of the lesions treated with methyl aminolevulinate PDT and surgery , 49 and 52 , respectively , showed complete clinical response at 3 months after treatment and were observed for long-term outcome evaluation . INTERVENTIONS Topical methyl aminolevulinate cream , 160 mg/g , applied for 3 hours before illumination ( 75 J/cm(2 ) of red light at 570 to 670 nm ) on 2 or 4 occasions ( 12 [ 23 % ] of 53 lesions ) ; or excision surgery . MAIN OUTCOME MEASURES Histologically confirmed lesion recurrence , sustained lesion complete response rate ( time-to-event analysis ) , and investigator assessment of cosmetic outcome , 5 years after the last treatment . RESULTS At 5 years , recurrence was documented in 7 ( 14 % ) of 49 lesions ( 95 % confidence interval [ CI ] , 6%-27 % ) treated with methyl aminolevulinate PDT vs 2 ( 4 % ) of 52 lesions ( 95 % CI , 1%-13 % ) treated with excision surgery ( P = .09 ) . Estimated sustained lesion complete response rates were 76 % ( 95 % CI , 59%-87 % ) and 96 % ( 95 % CI , 84%-99 % ) , respectively ( P = .01 ) . More patients treated with methyl aminolevulinate PDT than surgery had an excellent or good cosmetic outcome : 27 ( 87 % ) of 31 patients ( 95 % CI , 70%-96 % ) vs 19 ( 54 % ) of 35 patients ( 95 % CI , 37%-71 % ) ( P = .007 ) . CONCLUSIONS Long-term follow-up indicates superior efficacy of surgery to methyl aminolevulinate PDT in nodular basal cell carcinoma . However , methyl aminolevulinate PDT is also an effective treatment for this indication and exhibits a more favorable cosmetic outcome In a clinical trial of 172 patients at four medical centers , interferon alfa-2b ( 1.5 x 10(6 ) IU ) or a placebo was injected directly into biopsy-proved noduloulcerative or superficial basal cell carcinomas three times weekly for 3 weeks , for a cumulative dose of 13.5 million IU . Efficacy of treatment was determined at 16 to 20 weeks by examination of biopsy specimens that demonstrated cure of lesions in 86 % of interferon-treated patients and in only 29 % of placebo-treated patients . During the treatment course and follow-up , an initial inflammatory response was observed at the treatment sites , followed by diminished erythema , improvement in overall appearance , and a decrease in size of lesions . Side effects of treatment , mainly flu-like symptoms , were usually mild and transient and occurred more commonly in the interferon-treated group . Only three patients , all in the interferon-treated group , discontinued therapy because of side effects . One year after initiation of therapy , 81 % of interferon recipients and 20 % of those given the placebo remained tumor free . Noduloulcerative and superficial lesions were equally responsive to treatment with interferon . For some patients with noduloulcerative or superficial basal cell carcinomas , intralesional interferon alfa-2b may be an alternative , effective treatment BACKGROUND Basal cell carcinomas ( BCCs ) are usually treated with ablative procedures . A nonsurgical treatment alternative would be of value in selected patients . OBJECTIVE We evaluated the safety and efficacy of a new preparation for intralesional sustained-release chemotherapy with MPI 5003 , 5-Fluorouracil Therapeutic Implant , for treatment of BCCs . METHODS Two doses of intralesional MPI 5003 ( 0.25 and 0.5 ml ) were compared in a double-blind study of 20 patients with biopsy-proven BCC . One BCC per patient was treated weekly for up to 6 weeks and followed up monthly for 3 months until excisional biopsy for histologic examination . Before excision the cosmetic appearance of the test site was grade d. RESULTS Eighty percent of 10 BCCs treated with 0.5 ml of MPI 5003 had histologically confirmed cures as compared with 60 % of 10 tumors treated with the lower dose ( 0.25 ml ) . Cosmetic assessment s before excision were typically good to excellent . No systemic side effects occurred . CONCLUSION Results indicate the potential of MPI 5003 for targeted local chemotherapy for BCC BACKGROUND Superficial basal-cell carcinoma is most commonly treated with topical non-surgical treatments , such as photodynamic therapy or topical creams . Photodynamic therapy is considered the preferable treatment , although this has not been previously tested in a r and omised control trial . We assessed the effectiveness of photodynamic therapy compared with imiquimod or fluorouracil in patients with superficial basal-cell carcinoma . METHODS In this single blind , non-inferiority , r and omised controlled multicentre trial , we enrolled patients with a histologically proven superficial basal-cell carcinoma at seven hospitals in the Netherl and s. Patients were r and omly assigned to receive treatment with methylaminolevulinate photodynamic therapy ( MAL-PDT ; two sessions with an interval of 1 week ) , imiquimod cream ( once daily , five times a week for 6 weeks ) , or fluorouracil cream ( twice daily for 4 weeks ) . Follow-up was at 3 and 12 months post-treatment . Data were collected by one observer who was blinded to the assigned treatment . The primary outcome was the proportion of patients free of tumour at both 3 and 12 month follow up . A pre-specified non-inferiority margin of 10 % was used and modified intention-to-treat analyses were done . This trial is registered as an International St and ard R and omised controlled trial ( IS RCT N 79701845 ) . FINDINGS 601 patients were r and omised : 202 to receive MAL-PDT , 198 to receive imiquimod , and 201 to receive fluorouracil .  A year after treatment , 52 of 196 patients treated with MAL-PDT , 31 of 189 treated with imiquimod , and 39 of 198 treated with fluorouracil had tumour residue or recurrence . The proportion of patients tumour-free at both 3 and 12 month follow-up was 72.8 % ( 95 % CI 66.8 - 79.4 ) for MAL-PDT , 83.4 % ( 78.2 - 88.9 ) for imiquimod cream , and 80.1 % ( 74.7 - 85.9 ) for fluorouracil cream . The difference between  imiquimod and  MAL-PDT was 10.6 % ( 95 % CI 1.5 - 19.5 ; p=0.021 ) and 7.3 % ( -1.9 to 16.5 ; p=0.120 ) between fluorouracil and MAL-PDT , and between fluorouracil and imiquimod was -3.3 % ( -11.6 to 5.0 ; p=0.435 . For patients treated with MAL-PDT , moderate to severe pain and burning sensation were reported most often during the actual MAL-PDT session . For other local adverse reactions , local skin redness was most often reported as moderate or severe in all treatment groups . Patients treated with creams more often reported moderate to severe local swelling , erosion , crust formation , and itching of the skin than patients treated with MAL-PDT . In the MAL-PDT group no serious adverse events were reported . One patient treated with imiquimod and two patients treated with fluorouracil developed a local wound infection and needed additional treatment in the outpatient setting . INTERPRETATION Topical fluorouracil was non-inferior and imiquimod was superior to MAL-PDT for treatment of superficial basal-cell carcinoma . On the basis of these findings , imiquimod can be considered the preferred treatment , but all aspects affecting treatment choice should be weighted to select the best treatment for patients . FUNDING Grant of the Netherl and s Organization for Scientific Research ZONMW ( 08 - 82310 - 98 - 08626 ) Combinational cryosurgery during daily imiquimod application ( ' immunocryosurgery ' ) efficiently cures invading  basal cell carcinoma ( BCC ) . Since timing of the cryosurgery is considered crucial for effectiveness , our aim was to compare efficacy of two different timing schemes of the combination of cryosurgery and topical imiquimod : Cryosurgery ( a ) 2 weeks after ( Arm I ) vs ( b ) prior to the initiation of a 5 week daily imiquimod course ( Arm II ) . 16 patients with 21 BCC were recruited in this prospect i ve , r and omized , open-label trial . 14 patients with 17 BCC were evaluated ( Arm I : 7 patients /10 tumors vs Arm II : 7 patients /7 tumors ) during scheduled interim analysis at 6 month follow-up ( two patients dropped out , one non-compliant and one lost to follow up ) . The trial was revoked because study Arm I ( ' immunocryosurgery ' ) was significantly superior to Arm II ( adjuvant imiquimod ) in achieving tumor clearance ( 10/10 vs 3/7 tumors ; p=0.0147 ) and by overall treatment efficacy ( 9/10 vs 2/7 relapse-free tumors ; p=0.0345 ) . The same overall efficacy persisted after at least 18 months follow-up for those patients with tumor clearance after the trial treatment . The timing of cryosurgery during imiquimod application substantially determines the efficacy of this combinational approach in the treatment of BCC BACKGROUND Data suggest that photodynamic therapy using topical methyl aminolevulinate ( MAL PDT ) may be a noninvasive alternative to excisional surgery for nodular basal cell carcinoma ( BCC ) . In the studies described here , we investigated the histologic response , tolerability , and cosmetic outcome with MAL PDT for primary nodular BCC ( < or= 5 mm in depth ) . METHODS Two multicenter , r and omized , double-blind studies with similar design and procedures were conducted . After surface debridement and minor tumor debulking , MAL cream 160 mg/g  ( 66 patients with 75 lesions )  or placebo cream ( 65 patients with 75 lesions ) was applied for 3 h , followed by illumination with broad-spectrum red light ( 75 J/cm(2 ) , 570 - 670 nm ) . This was repeated 7 days later . Lesions with a partial response ( > or= 50 % reduction in greatest diameter ) at 3 months were re-treated ( 21 % ) . Treatment sites were excised at 3 months ( clinical nonresponders ) or 6 months ( clinical responders ) after the last treatment . RESULTS Histologically verified lesion complete response rates were higher with MAL PDT than with placebo [ 73 % ( 55/75 ) vs. 27 % ( 20/75 ) ] . Treatment was most effective for facial lesions ( 89 % complete response ) . Cosmetic outcome was good or excellent in 98 % of evaluable , completely responding lesions treated with MAL PDT . CONCLUSION Although longer follow-up studies are required , these promising data indicate the potential of topical MAL PDT as a noninvasive treatment alternative for nodular BCC Photodynamic therapy ( PDT ) using topical porphyrin-precursors is a promising treatment for  superficial basal cell carcinoma ( sBCC ) , but it needs further optimization . The aim of this study was to compare 5-year lesion ( 
    Output:
    