***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: Summary Background The international st and ard radiotherapy schedule for early breast cancer delivers 50 Gy in 25 fractions of 2·0 Gy over 5 weeks , but there is a long history of non-st and ard regimens delivering a lower total dose using fewer , larger fractions ( hypofractionation ) . We aim ed to test the benefits of radiotherapy schedules using fraction sizes larger than 2·0 Gy in terms of local-regional tumour control , normal tissue responses , quality of life , and economic consequences in women prescribed post-operative radiotherapy . Methods Between 1999 and 2001 , 2215 women with early breast cancer ( pT1 - 3a pN0 - 1 M0 ) at 23 centres in the UK were r and omly assigned after primary surgery to receive 50 Gy in 25 fractions of 2·0 Gy over 5 weeks or 40 Gy in 15 fractions of 2·67 Gy over 3 weeks . Women were eligible for the trial if they were aged over 18 years , did not have an immediate reconstruction , and were available for follow-up . R and omisation method was computer generated and was not blinded . The protocol -specified principal endpoints were local-regional tumour relapse , defined as reappearance of cancer at irradiated sites , late normal tissue effects , and quality of life . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N59368779 . Findings 1105 women were assigned to the 50 Gy group and 1110 to the 40 Gy group . After a median follow up of 6·0 years ( IQR 5·0–6·2 ) the rate of local-regional tumour relapse at 5 years was 2·2 % ( 95 % CI 1·3–3·1 ) in the 40 Gy group and 3·3 % ( 95 % CI 2·2 to 4·5 ) in the 50 Gy group , representing an absolute difference of −0·7 % ( 95 % CI −1·7 % to 0·9%)—ie , the absolute difference in local-regional relapse could be up to 1·7 % better and at most 1 % worse after 40 Gy than after 50 Gy . Photographic and patient self- assessment s indicated lower rates of late adverse effects after 40 Gy than after 50 Gy . Interpretation A radiation schedule delivering 40 Gy in 15 fractions seems to offer rates of local-regional tumour relapse and late adverse effects at least as favourable as the st and ard schedule of 50 Gy in 25 fractions A pilot study has been conducted to examine a new approach to the treatment of operable breast carcinoma . 27 patients with tumours measuring up to 4 cm in diameter have been treated by tumourectomy , axillary clearance and high dose iridium-192 implant ( 55 Gy ) without any external beam radiotherapy . This enabled the entire local primary treatment of the breast carcinoma to be given in five days . The technique was compatible with adjuvant chemotherapy for those with involved axillary nodes . Local complications have been few and locoregional control has to date been satisfactory . With a relatively short median follow-up of 27 months , cosmesis was objective ly rated as good or excellent in over 80 % of cases and subjectively rated good/excellent in 96 % . High dose brachytherapy now requires testing in a prospect i ve clinical trial to determine whether it is as effective as st and ard breast conservation techniques for management of early breast cancer In 1976 we began a r and omized trial to evaluate breast conservation by a segmental mastectomy in the treatment of Stage I and II breast tumors less than or equal to 4 cm in size . The operation removes only sufficient tissue to ensure that margins of resected specimens are free of tumor . Women were r and omly assigned to total mastectomy , segmental mastectomy alone , or segmental mastectomy followed by breast irradiation . All patients had axillary dissections , and patients with positive nodes received chemotherapy .  Life-table estimates based on data from 1843 women indicated that treatment by segmental mastectomy , with or without breast irradiation , result ed in disease-free , distant-disease-free , and overall survival at five years that was no worse than that after total breast removal . In fact , disease-free survival after segmental mastectomy plus radiation was better than disease-free survival after total mastectomy ( P = 0.04 ) , and overall survival after segmental mastectomy , with or without radiation , was better than overall survival after total mastectomy ( P = 0.07 , and 0.06 , respectively ) . A total of 92.3 per cent of women treated with radiation remained free of breast tumor at five years , as compared with 72.1 per cent of those receiving no radiation ( P less than 0.001 ) . Among patients with positive nodes 97.9 per cent of women treated with radiation and 63.8 per cent of those receiving no radiation remained tumor-free ( P less than 0.001 ) , although both groups received chemotherapy . We conclude that segmental mastectomy , followed by breast irradiation in all patients and adjuvant chemotherapy in women with positive nodes , is appropriate therapy for Stage I and II breast tumors less than or equal to 4 cm , provided that margins of resected specimens are free of tumor Abstract In a clinical trial , tumour doses of 380 rads given twice weekly were compared with 200 rads given five times per week . The overall treatment time and other parameters of treatment remained the same and both regimes were tested on the same patient . The skin erythema was observed in six patients and tumour regression in five . Two hundred rads given five times per week appeared to be biologically more effective than 380 rads given twice weekly . A new trial is to be started raising the twice weekly dose to 400 rads A prospect i ve assessment of late changes in breast appearance in 559 patients after tumour excision and radiotherapy for early breast cancer noted a strong association with breast size . Only 3/48 ( 6 % ) patients with small breasts developed moderate or severe late changes compared with 94/423 ( 22 % ) with medium sized breasts and 34/88 ( 39 % ) patients with large breasts ( p < 0.001 ) . One possibility is that greater radiation changes are related to greater dose inhomogeneity in women with large breasts . To explore this hypothesis , radiation dose distributions were assessed in a separate group of 37 women in whom three-level transverse computer tomographic images of the breast in the treatment position were available . A significant correlation was found between breast size and dose inhomogeneity which may account for the marked changes in breast appearance reported in women with large breasts Changes in the epidermal basal cell density ( BCD ) in human skin were determined during and immediately after fractionate radiotherapy . The basal cells are one of the target cell types responsible for acute skin reactions and measuring the BCD is a histological method for study ing the time course and degree of reaction . Thirty-two patients with breast cancer participated in this study . They received postmastectomy radiotherapy to the thoracic wall . A 3-mm punch biopsy was taken from the irradiation field once a week for 6 - 10 weeks and the linear basal cell density was determined . St and ard fractionation at two different dose levels ( 40 and 50 Gy ) as well as hypofractionation and accelerated treatment have been investigated . For the first 3 weeks we found a constant decline in the BCD ( about 0.8%/day ) , independent of dose and fractionation schedule . Using the nadir value as endpoint we found a dose-response relationship between 40 and 50 Gy , and for total effect (TE)-values in the range 430 - 1015 . Compared to st and ard fractionation , hypofractionation showed somewhat less effect and accelerated fractionation showed significantly less effect . The reduced effect of accelerated fractionation is interpreted as a result of lack of cell cycle redistribution of cells between the two daily fractions in this type of tissue . The removal rate of dead or doomed cells could also affect the results for schedules with different overall time . The results of BCD were also compared to erythema . ( ABSTRACT TRUNCATED AT 250 WORDS PURPOSE To evaluate if chemotherapy ( CT ) dose-intensification jeopardizes radiotherapy ( RT ) dose-intensity ( DI ) . PATIENTS AND METHODS From 1992 to 1997 , 247 stage I-II breast cancer patients , treated with conserving surgery , were treated at the National Cancer Institute of Genoa in a r and omized study comparing the same CEF regimen delivered every two weeks ( CEF14 ) or three weeks ( CEF21 ) . RT was applied to the residual breast at a total dose of 50 Gy in five weeks . Allowance was made for treatment at 2.3 Gy per fraction in order to compensate for gaps ( hypofractionation ) . Radiotherapy DI was expressed as the average total dose received each week , i.e. , ' weekly dose-rate ' ( WDR ) . The effect of various tumour , treatment and patient-related factors on the endpoint ( a delivered WDR of RT < 9.5 Gy ) was investigated by univariate analysis . Factors found to have P-value < or = 0.20 were entered in multivariate analysis . RESULTS All but three patients ( 244 of 247 , 98.8 % ) received a cumulative total dose of RT within + /- 10 % of that planned . Moreover , most of them ( 197 of 247 , 79.8 % ) received an average WDR of > or = 9.5 Gy/wk . With univariate analysis the probability of WDR < 9.5 Gy/wk significantly correlated with age , menopausal status , concomitant administration of RT and CT , and white blood cell toxicity . Moreover , a positive effect on WDR was found in patients treated at 2.3 Gy per fraction . The type of treatment ( CEF14 vs. CEF21 ) did not affect the probability of WDR < 9.5 Gy/wk . With multivariate analysis , age ( < or = 55 vs. > 55 years , RR = 3.99 , 95 % CI : 1.89 - 8.42 , P = 0.0003 ) , RT fractionation ( conventional vs. hypofractionation , RR = 0.32 , 95 % CI : 0.15 - 0.68 , P = 0.017 ) and WBC toxicity ( none vs. some , RR = 1.54 , 95 % CI : 1.06 - 2.22 , P = 0.027 ) were independent predictors of WDR < 9.5 Gy . Regarding the CT-RT overlap , patients receiving more than two cycles of chemotherapy during radiotherapy had an increased risk of RT delay compared to other patients ( RR = 3.74 , 95 % CI : 1.44 - 9.48 , P = 0.0063 ) . CONCLUSIONS There is no evidence of a direct effect of CT dose-density on dose-intensity of RT . However , the concomitant use of CT and RT reduces the possibility of giving a full dose-intensity of RT A preliminary review of results from a r and om clinical trial which compared radical mastectomy with simple mastectomy plus radical radiotherapy in a group of 395 breast cancer patients has shown a nonsignificant trend toward a higher survival rate under radical mastectomy and differences in the pattern of complications . Under either treatment mortality rate increased linearly as a function of tumor size up to 5 - 6 cm and was higher among older postmenopausal women . A discriminant function based on measurements of 24-hour urine excretion of 17-hydroxycorticosteroids and etiocholanolone was developed which correlated closely with failure to respond to major endocrine procedures and reduced survival rate . Clinical trials follow-up and data analysis are continuing We report a single-centre prospect i ve audit of 29 lung cancer patients who were awaiting radical ( potentially curative ) radiotherapy .  This was the total number assessed as suitable for radical treatment by one consultant during 1999 . At the time of assessment they had been newly diagnosed and staged with a computed tomographic ( CT ) scan of chest . They had a subsequent CT scan prior to starting treatment for the purpose of planning the radiation fields . We have now measured tumour size on the diagnostic scans and compared this with the size on the planning scans . We have documented the delay between diagnostic and planning CT scanning and the total time between first hospital visit and starting treatment . Two patients had progression of symptoms while on the waiting list , making them unfit for radical treatment , and another four had tumour progression on planning CT such that the tumour volume was too large for radical treatment . Therefore , 21 % of potentially curable patients became incurable on the waiting list . The delay between diagnostic and planning CT scans ranged from 18 to 131 days ( median 54 ) , with increases in the cross-sectional tumour size over that period ranging zero to 373 % . The delay between the first hospital visit and starting treatment was 35 - 187 days ( median 94 ) ; between the date of the radiotherapy request and the starting date for treatment it was 23 - 61 days ( median 44 ) . Limited access to specialists is the reason most often advanced for the poor performance of the UK in treating lung cancer . This study demonstrates that , even for the select minority of patients who have specialist referral and are deemed suitable for potentially curative treatment , the outcome is prejudiced by waiting times that allow tumour progression A cohort of 63 patients participating in a prospect ively r and omized trial evaluating two different radiotherapy regimens and adjuvant tamoxifen in the conservative management of early breast cancer were monitored by a series of psychological measures . The aim was to determine whether there was any difference between the radiotherapy schedules in terms of their 
    Output:
    
We have evidence from two high quality r and omised trials that the use of unconventional fractionation regimes ( greater than 2 Gy per fraction ) does not affect breast appearance or toxicity and does not seem to affect local recurrence for selected women treated with breast conserving therapy .