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: Patients with advanced cervical carcinoma are treated routinely with radiotherapy and cisplatin‐containing chemotherapy . It has been shown that hyperthermia can improve the results of both radiotherapy and cisplatin . In the current study , the feasibility and efficacy of the combination of all three modalities was studied in previously untreated patients with cervical carcinoma Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more To clarify the role of thermoradiotherapy for FIGO Stage IIIB cervical carcinomas , both the clinical response and survival of patients treated with radio- or thermoradiotherapy  were investigated . Forty patients with Stage IIIB uterine cervix carcinoma were treated with external beam irradiation to the pelvis , combined with iridium 192 high-dose-rate intracavitary brachytherapy . All patients were divided r and omly into the following two groups : the radiotherapy ( RT ) group of 20 patients , who underwent radiotherapy alone ; and the thermoradiotherapy ( TRT ) group of 20 patients , who underwent three sessions of hyperthermia in addition to radiotherapy . The primary endpoint of this study was local complete response and survival . A complete response was achieved in 50 % ( 10 of 20 ) in the RT group versus 80 % ( 16 of 20 ) in the TRT group ( p = 0.048 ) . The 3-year overall survival and disease-free survival of the patients who were treated with TRT ( 58.2 and 63.6 % ) were better than those of the patients treated with RT ( 48.1 and 45 % ) , but these differences were not significant . The 3-year local relapse-free survival of the patients who were treated with TRT ( 79.7 % ) was significantly better than that of the patients treated with RT ( 48.5 % ) ( p = 0.048 ) . TRT , as delivered in this trial , was well tolerated and did not significantly add to either the relevant clinical acute or long-term toxicity over radiation alone . TRT result ed in a better treatment response and 3-year local relapse-free survival rate than RT for patients with FIGO Stage IIIB cervical carcinoma In 1986 , 25 patients with stage II and III carcinoma of the cervix were treated by a combination of radiation and local hyperthermia using an endotract intravaginal applicator . Another 25 patients were treated with radiation alone . Both groups were followed up for a minimum period of 18 months . The acute and long-term toxicity of local hyperthermia was closely monitored . Our study shows that whereas local hyperthermia adds significantly to the local control achieved with radiation alone , it is not in any way associated with any significant short- or long-term toxicity , and does not enhance the radiation reactions PURPOSE The local failure rate in patients with locoregionally advanced cervical cancer is 41 - 72 % after radiotherapy ( RT ) alone , whereas local control is a prerequisite for cure . The Dutch Deep Hyperthermia Trial showed that combining RT with hyperthermia ( HT ) improved 3-year local control rates of 41 - 61 % , as we reported earlier . In this study , we evaluate long-term results of the Dutch Deep Hyperthermia Trial after 12 years of follow-up . METHODS AND MATERIAL S From 1990 to 1996 , a total of 114 women with locoregionally advanced cervical carcinoma were r and omly assigned to RT or RT+HT . The RT was applied to a median total dose of 68 Gy . The HT was given once weekly . The primary end point was local control . Secondary end points were overall survival and late toxicity . RESULTS At the 12-year follow-up , local control remained better in the RT+HT group ( 37 % vs. 56 % ; p=0.01 ) . Survival was persistently better after 12 years : 20 % ( RT ) and 37 % ( RT+HT ; p=0.03 ) . World Health Organization ( WHO ) performance status was a significant prognostic factor for local control . The WHO performance status , International Federation of Gynaecology and Obstetrics ( FIGO ) stage , and tumor diameter were significant for survival . The benefit of HT remained significant after correction for these factors . European Organization for Research and Treatment of Cancer Grade 3 or higher radiation-induced late toxicities were similar in both groups . CONCLUSIONS For locoregionally advanced cervical cancer , the addition of HT to RT result ed in long-term major improvement in local control and survival without increasing late toxicity . This combined treatment should be considered for patients who are unfit to receive chemotherapy . For other patients , the optimal treatment strategy is the subject of ongoing research OBJECTIVE To evaluate if pretreatment HPV titers in cancer cervix could predict radiation response and survival outcomes . METHODS Twenty-one patients of cancer cervix were treated by radiotherapy ( RT ) alone .  HPV titers were estimated using DNA Hybrid Capture II test . Loco-regional response at 1 month of RT -- complete or partial response ( CR and PR respectively ) and survival outcomes --local disease-free ( LDFS ) , disease-free ( DFS ) and overall ( OS ) survivals were evaluated against pre- and posttreatment HPV titers . RESULTS Pretreatment HPV titers ranged from 0.81 to 3966.10 RLU/cut off ( mean + /- SD : 1264.39 + /- 1148.22 , median : 1129.98 ) . Of the demographic features evaluated , mean HPV titers were significantly different only for patients achieving CR or PR at completion of RT ( mean + /- SD for CR vs. PR : 1616.31 + /- 1146.86 vs. 384.57 + /- 538.80 , P = 0.022 ) . HPV titers at end of RT ranged from 0.12 to 487.42 RLU/cut off ( mean + /- SD : 37.31 + /- 108.60 , median : 2.33 ) . Patients with higher pretreatment HPV titers ( > 1000 RLU/cutoff ) had a higher CR ( P = 0.022 ) and better survival compared to those with < or = 1000 RLU/cutoff ( LDFS , P = 0.004 ; DFS , P = 0.005 ; OS , P = 0.012 ) . At completion of RT , those having > or = 99.5 % fall in HPV had superior survival outcomes than those with < 99.5 % reduction ( LDFS , P = 0.002 ; DFS , P = 0.002 ; OS , P = 0.004 ) . CONCLUSIONS Higher pretreatment HPV titers ( > 1000 RLU/cutoff ) could be considered as a predictor of radiotherapy response and survival in cancer cervix . A reduction in these titers to 99.5 % of their baseline values at end of radiotherapy is also associated with better survival outcomes Background and purpose : The aim of this study was to investigate whether hyperthermia ( HT ) combined with interstitial brachytherapy ( ISBT ) has any influence on acute and late side effects in patients with advanced cervical cancer .  Local control ( LC ) and disease-free survival ( DFS ) were also analysed . Material s and methods : Following the completion of radiochemotherapy , patients with cervical cancer ( FIGO stages I – III ) were assigned to two treatment groups , either ISBT combined with interstitial hyperthermia ( ISHT ) or ISBT alone as a control group . Selection criterion for the ISBT combined with HT group was advanced cervical cancer with poor response to external beam radiotherapy . A total of 76 patients were included in the statistical analysis . Once a week , HT ( at a temperature above 42.5 ° C ) was administered for 45 min before and during high dose rate ( HDR ) brachytherapy ( BT ) in 43 patients . Four HT treatments were administered . Results : The median follow-up time was 43 months ( range 4–73 months ) . Significant differences were not observed for the distribution of early and late complications between the HT and no HT groups . Despite this , LC was similar in both groups . The 5-year DFS for the BT and BT + HT groups was 73.6 % and 65.8 % , respectively . The 5-year LC for the BT and BT + HT groups was 89 % and 83 % , respectively . For the majority of patients the maximum temperature level of 44–45 ° C was achieved during the ISHT . Conclusions : ISHT is well tolerated and does not affect treatment-related early or late complications BACKGROUND Chemoradiation ( RT-CT ) is st and ard treatment for locally advanced cervical cancer ( LACC ) . This study tried to establish if radiotherapy combined with hyperthermia ( RT-HT ) should be preferred in bulky and /or FIGO-stage ⩾III . METHODS In this open-label , multicenter r and omized trial , patients with LACC were r and omly assigned by a computer-generated , biased coin minimization technique to RT-CT or RT-HT . Central r and omization was done with stratification by FIGO-stage , tumour diameter and nodal status . Primary endpoint was event free survival ( EFS ) . Secondary endpoints were pelvic recurrence free survival ( PRFS ) , overall survival ( OS ) and treatment related toxicity . Analysis was done by intention to treat . RESULTS The trial was closed prematurely ( 87 of 376 planned patients enrolled : 43 RT-CT ; 44 RT-HT ) . Median follow-up time was 7.1 years . The cumulative incidence of an event was 33 % in the RT-CT group and 35 % in the RT-HT group . The corresponding hazard rate ( HR ) for EFS was 1.15 ( CI : 0.56 - 2.36 , p=0.7 ) . Also the hazards for PRFS ( 0.94 ; CI 0.36 - 2.44 ) and OS ( 1.04 ; CI 0.48 - 2.23 ) at 5 years were comparable between both treatment arms as was grade ⩾3 radiation related late toxicity  ( 6 RT-CT and 5 RT-HT patients ) . CONCLUSION After 25 % of intended accrual , data suggest comparable outcome for RT-CT and RT-HT Background : Advanced cervical cancer is routinely treated with radiotherapy and cisplatin-containing chemotherapy . Hyperthermia has been shown to improve the results of both radiotherapy and cisplatin . The feasibility of the combination of all three modalities was demonstrated and reported in a study of 68 previously untreated cervical cancer patients in 2005 . Long-term follow-up is presented here . Methods : Sixty-eight patients with advanced cervical cancer were prospect ively registered in the USA , Norway and the Netherl and s , and treated with a combination of radiotherapy ( external beam radiotherapy and brachytherapy for a biologically effective dose of at least 86.7 Gy ) , chemotherapy ( at least four courses of weekly cisplatin ( 40 mg/m2 ) ) and locoregional hyperthermia ( four weekly sessions ) . Long-term follow-up was gathered and recurrence-free survival ( RFS ) and overall survival ( OS ) curves and survival estimates were obtained . Results : Median follow-up was 81 months . Tumours in 28 patients have recurred , 21 of whom have died . Five-year RFS from the day of registration in the study is 57.5 % ( 95%CI : 46.6–71.0 ) and five-year OS is 66.1 % ( 95%CI : 55.1–79.3 ) . Differences between countries can be explained by patient characteristics . Conclusion : The long-term survival results of the combination of full-dose radiotherapy , chemotherapy and hyperthermia fall well within previous reports for this patient group in r and omised trials . The small trial size and lack of r and omisation do not permit further interpretation PURPOSE Hyperthermia can be used to enhance the effects of radiation , and a combined treatment may , in some circumstances , be an advantage . Uterine cervical cancer is very common in developing countries . The control of locally advanced pelvic tumors is difficult with conventional treatment modalities . Based upon the biologic rationale and in view of the recent advances in heating and thermometry techniques , radiotherapy in combination with hyperthermia was investigated in a multi-institutional prospect i ve r and omized trial sponsored by the International Atomic Energy Agency . The primary purpose was to clarify whether the combination of hyperthermia and radiotherapy improves the rate of local control , compared with radiotherapy alone . METHODS AND MATERIAL S A total of 110 patients with biopsy-proven , locally advanced carcinoma of the uterine cervix were r and omized to treatment by radiotherapy with or without hyperthermia .  The patients were stratified by institution , stage , and histologic type . Each patient received external beam radiation therapy and brachytherapy . For the patients r and omized to receive hyperthermia , a minimum of five sessions ( 60 min each , once per week ) were administered , employing a radiofrequency ( RF ) capacitive heating device . Intratumoral temperature was measured at the first hyperthermic treatment , and at least once more during the course of 
    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: Patients with advanced cervical carcinoma are treated routinely with radiotherapy and cisplatin‐containing chemotherapy . It has been shown that hyperthermia can improve the results of both radiotherapy and cisplatin . In the current study , the feasibility and efficacy of the combination of all three modalities was studied in previously untreated patients with cervical carcinoma Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more To clarify the role of thermoradiotherapy for FIGO Stage IIIB cervical carcinomas , both the clinical response and survival of patients treated with radio- or thermoradiotherapy  were investigated . Forty patients with Stage IIIB uterine cervix carcinoma were treated with external beam irradiation to the pelvis , combined with iridium 192 high-dose-rate intracavitary brachytherapy . All patients were divided r and omly into the following two groups : the radiotherapy ( RT ) group of 20 patients , who underwent radiotherapy alone ; and the thermoradiotherapy ( TRT ) group of 20 patients , who underwent three sessions of hyperthermia in addition to radiotherapy . The primary endpoint of this study was local complete response and survival . A complete response was achieved in 50 % ( 10 of 20 ) in the RT group versus 80 % ( 16 of 20 ) in the TRT group ( p = 0.048 ) . The 3-year overall survival and disease-free survival of the patients who were treated with TRT ( 58.2 and 63.6 % ) were better than those of the patients treated with RT ( 48.1 and 45 % ) , but these differences were not significant . The 3-year local relapse-free survival of the patients who were treated with TRT ( 79.7 % ) was significantly better than that of the patients treated with RT ( 48.5 % ) ( p = 0.048 ) . TRT , as delivered in this trial , was well tolerated and did not significantly add to either the relevant clinical acute or long-term toxicity over radiation alone . TRT result ed in a better treatment response and 3-year local relapse-free survival rate than RT for patients with FIGO Stage IIIB cervical carcinoma In 1986 , 25 patients with stage II and III carcinoma of the cervix were treated by a combination of radiation and local hyperthermia using an endotract intravaginal applicator . Another 25 patients were treated with radiation alone . Both groups were followed up for a minimum period of 18 months . The acute and long-term toxicity of local hyperthermia was closely monitored . Our study shows that whereas local hyperthermia adds significantly to the local control achieved with radiation alone , it is not in any way associated with any significant short- or long-term toxicity , and does not enhance the radiation reactions PURPOSE The local failure rate in patients with locoregionally advanced cervical cancer is 41 - 72 % after radiotherapy ( RT ) alone , whereas local control is a prerequisite for cure . The Dutch Deep Hyperthermia Trial showed that combining RT with hyperthermia ( HT ) improved 3-year local control rates of 41 - 61 % , as we reported earlier . In this study , we evaluate long-term results of the Dutch Deep Hyperthermia Trial after 12 years of follow-up . METHODS AND MATERIAL S From 1990 to 1996 , a total of 114 women with locoregionally advanced cervical carcinoma were r and omly assigned to RT or RT+HT . The RT was applied to a median total dose of 68 Gy . The HT was given once weekly . The primary end point was local control . Secondary end points were overall survival and late toxicity . RESULTS At the 12-year follow-up , local control remained better in the RT+HT group ( 37 % vs. 56 % ; p=0.01 ) . Survival was persistently better after 12 years : 20 % ( RT ) and 37 % ( RT+HT ; p=0.03 ) . World Health Organization ( WHO ) performance status was a significant prognostic factor for local control . The WHO performance status , International Federation of Gynaecology and Obstetrics ( FIGO ) stage , and tumor diameter were significant for survival . The benefit of HT remained significant after correction for these factors . European Organization for Research and Treatment of Cancer Grade 3 or higher radiation-induced late toxicities were similar in both groups . CONCLUSIONS For locoregionally advanced cervical cancer , the addition of HT to RT result ed in long-term major improvement in local control and survival without increasing late toxicity . This combined treatment should be considered for patients who are unfit to receive chemotherapy . For other patients , the optimal treatment strategy is the subject of ongoing research OBJECTIVE To evaluate if pretreatment HPV titers in cancer cervix could predict radiation response and survival outcomes . METHODS Twenty-one patients of cancer cervix were treated by radiotherapy ( RT ) alone .  HPV titers were estimated using DNA Hybrid Capture II test . Loco-regional response at 1 month of RT -- complete or partial response ( CR and PR respectively ) and survival outcomes --local disease-free ( LDFS ) , disease-free ( DFS ) and overall ( OS ) survivals were evaluated against pre- and posttreatment HPV titers . RESULTS Pretreatment HPV titers ranged from 0.81 to 3966.10 RLU/cut off ( mean + /- SD : 1264.39 + /- 1148.22 , median : 1129.98 ) . Of the demographic features evaluated , mean HPV titers were significantly different only for patients achieving CR or PR at completion of RT ( mean + /- SD for CR vs. PR : 1616.31 + /- 1146.86 vs. 384.57 + /- 538.80 , P = 0.022 ) . HPV titers at end of RT ranged from 0.12 to 487.42 RLU/cut off ( mean + /- SD : 37.31 + /- 108.60 , median : 2.33 ) . Patients with higher pretreatment HPV titers ( > 1000 RLU/cutoff ) had a higher CR ( P = 0.022 ) and better survival compared to those with < or = 1000 RLU/cutoff ( LDFS , P = 0.004 ; DFS , P = 0.005 ; OS , P = 0.012 ) . At completion of RT , those having > or = 99.5 % fall in HPV had superior survival outcomes than those with < 99.5 % reduction ( LDFS , P = 0.002 ; DFS , P = 0.002 ; OS , P = 0.004 ) . CONCLUSIONS Higher pretreatment HPV titers ( > 1000 RLU/cutoff ) could be considered as a predictor of radiotherapy response and survival in cancer cervix . A reduction in these titers to 99.5 % of their baseline values at end of radiotherapy is also associated with better survival outcomes Background and purpose : The aim of this study was to investigate whether hyperthermia ( HT ) combined with interstitial brachytherapy ( ISBT ) has any influence on acute and late side effects in patients with advanced cervical cancer .  Local control ( LC ) and disease-free survival ( DFS ) were also analysed . Material s and methods : Following the completion of radiochemotherapy , patients with cervical cancer ( FIGO stages I – III ) were assigned to two treatment groups , either ISBT combined with interstitial hyperthermia ( ISHT ) or ISBT alone as a control group . Selection criterion for the ISBT combined with HT group was advanced cervical cancer with poor response to external beam radiotherapy . A total of 76 patients were included in the statistical analysis . Once a week , HT ( at a temperature above 42.5 ° C ) was administered for 45 min before and during high dose rate ( HDR ) brachytherapy ( BT ) in 43 patients . Four HT treatments were administered . Results : The median follow-up time was 43 months ( range 4–73 months ) . Significant differences were not observed for the distribution of early and late complications between the HT and no HT groups . Despite this , LC was similar in both groups . The 5-year DFS for the BT and BT + HT groups was 73.6 % and 65.8 % , respectively . The 5-year LC for the BT and BT + HT groups was 89 % and 83 % , respectively . For the majority of patients the maximum temperature level of 44–45 ° C was achieved during the ISHT . Conclusions : ISHT is well tolerated and does not affect treatment-related early or late complications BACKGROUND Chemoradiation ( RT-CT ) is st and ard treatment for locally advanced cervical cancer ( LACC ) . This study tried to establish if radiotherapy combined with hyperthermia ( RT-HT ) should be preferred in bulky and /or FIGO-stage ⩾III . METHODS In this open-label , multicenter r and omized trial , patients with LACC were r and omly assigned by a computer-generated , biased coin minimization technique to RT-CT or RT-HT . Central r and omization was done with stratification by FIGO-stage , tumour diameter and nodal status . Primary endpoint was event free survival ( EFS ) . Secondary endpoints were pelvic recurrence free survival ( PRFS ) , overall survival ( OS ) and treatment related toxicity . Analysis was done by intention to treat . RESULTS The trial was closed prematurely ( 87 of 376 planned patients enrolled : 43 RT-CT ; 44 RT-HT ) . Median follow-up time was 7.1 years . The cumulative incidence of an event was 33 % in the RT-CT group and 35 % in the RT-HT group . The corresponding hazard rate ( HR ) for EFS was 1.15 ( CI : 0.56 - 2.36 , p=0.7 ) . Also the hazards for PRFS ( 0.94 ; CI 0.36 - 2.44 ) and OS ( 1.04 ; CI 0.48 - 2.23 ) at 5 years were comparable between both treatment arms as was grade ⩾3 radiation related late toxicity  ( 6 RT-CT and 5 RT-HT patients ) . CONCLUSION After 25 % of intended accrual , data suggest comparable outcome for RT-CT and RT-HT Background : Advanced cervical cancer is routinely treated with radiotherapy and cisplatin-containing chemotherapy . Hyperthermia has been shown to improve the results of both radiotherapy and cisplatin . The feasibility of the combination of all three modalities was demonstrated and reported in a study of 68 previously untreated cervical cancer patients in 2005 . Long-term follow-up is presented here . Methods : Sixty-eight patients with advanced cervical cancer were prospect ively registered in the USA , Norway and the Netherl and s , and treated with a combination of radiotherapy ( external beam radiotherapy and brachytherapy for a biologically effective dose of at least 86.7 Gy ) , chemotherapy ( at least four courses of weekly cisplatin ( 40 mg/m2 ) ) and locoregional hyperthermia ( four weekly sessions ) . Long-term follow-up was gathered and recurrence-free survival ( RFS ) and overall survival ( OS ) curves and survival estimates were obtained . Results : Median follow-up was 81 months . Tumours in 28 patients have recurred , 21 of whom have died . Five-year RFS from the day of registration in the study is 57.5 % ( 95%CI : 46.6–71.0 ) and five-year OS is 66.1 % ( 95%CI : 55.1–79.3 ) . Differences between countries can be explained by patient characteristics . Conclusion : The long-term survival results of the combination of full-dose radiotherapy , chemotherapy and hyperthermia fall well within previous reports for this patient group in r and omised trials . The small trial size and lack of r and omisation do not permit further interpretation PURPOSE Hyperthermia can be used to enhance the effects of radiation , and a combined treatment may , in some circumstances , be an advantage . Uterine cervical cancer is very common in developing countries . The control of locally advanced pelvic tumors is difficult with conventional treatment modalities . Based upon the biologic rationale and in view of the recent advances in heating and thermometry techniques , radiotherapy in combination with hyperthermia was investigated in a multi-institutional prospect i ve r and omized trial sponsored by the International Atomic Energy Agency . The primary purpose was to clarify whether the combination of hyperthermia and radiotherapy improves the rate of local control , compared with radiotherapy alone . METHODS AND MATERIAL S A total of 110 patients with biopsy-proven , locally advanced carcinoma of the uterine cervix were r and omized to treatment by radiotherapy with or without hyperthermia .  The patients were stratified by institution , stage , and histologic type . Each patient received external beam radiation therapy and brachytherapy . For the patients r and omized to receive hyperthermia , a minimum of five sessions ( 60 min each , once per week ) were administered , employing a radiofrequency ( RF ) capacitive heating device . Intratumoral temperature was measured at the first hyperthermic treatment , and at least once more during the course of 
    Output:
    