Background Adjuvant radiotherapy for rectal cancer has beenextensively studied, but no trial has unequivocally demonstratedimproved overall survival with radiotherapy, despite a reductionin the rate of local recurrence.
Methods Between March 1987 and February 1990, we randomly assigned1168 patients younger than 80 years of age who had resectablerectal cancer to undergo preoperative irradiation (25 Gy deliveredin five fractions in one week) followed by surgery within oneweek or to have surgery alone.
Results The irradiation did not increase postoperative mortality.After five years of follow-up, the rate of local recurrencewas 11 percent (63 of 553 patients) in the group that receivedradiotherapy before surgery and 27 percent (150 of 557) in thegroup treated with surgery alone (P<0.001). This differencewas found in all subgroups defined according to Dukes' stage.The overall five-year survival rate was 58 percent in the radiotherapy-plus-surgerygroup and 48 percent in the surgery-alone group (P = 0.004).The cancer-specific survival rates at nine years among patientstreated with curative resection were 74 percent and 65 percent,respectively (P = 0.002).
Conclusions A short-term regimen of high-dose preoperative radiotherapyreduces rates of local recurrence and improves survival amongpatients with resectable rectal cancer.
The value of adding radiotherapy to surgery in the treatmentof patients with resectable rectal cancer has been assessedin trials using either preoperative1,2,3,4,5,6 or postoperative7,8,9,10irradiation. Lower rates of local recurrence have been foundwith radiotherapy in most of these trials, especially thoseusing preoperative irradiation. In a randomized trial in theUppsala region of Sweden, it was found that preoperative irradiationwas more effective than postoperative therapy, even though thedose of postoperative radiation was higher.11 However, no trialhas yet shown that, as compared with surgery alone, adjuvantpreoperative radiotherapy significantly improves overall survival.1,2,6,12A meta-analysis of all the controlled trials on this subjectpublished before 1986 found a marginally positive effect ofradiotherapy on survival.13 A survival benefit was also foundwith a combination of postoperative radiotherapy and prolongedchemotherapy9; in another trial, postoperative chemotherapyalone, but not radiotherapy, improved survival.8
Preoperative irradiation is more "dose-effective" than postoperativeradiotherapy14; that is, a higher dose is needed postoperativelyto reduce rates of local recurrence to the same extent as preoperativeradiation. Nevertheless, preoperative treatment has not beenroutinely recommended,15 mainly because it has not been shownto improve overall survival and because in some trials it hasbeen associated with increased postoperative mortality.2,6
We conducted the present trial to determine whether preoperativeradiotherapy with a three-beam or four-beam technique couldbe given to patients younger than 80 years of age without increasingpostoperative mortality, to substantiate the previously observedreduction in the rate of local recurrence with radiotherapy,and to investigate the effects of the treatment on survival.In this report, we present rates of local recurrence and survivalafter a minimal follow-up of five years. The local-recurrencerates after a minimum of two years of follow-up have been reportedpreviously.16
Methods
Randomization
Patients were randomly assigned to treatment groups, with stratificationaccording to hospital, by telephone contact with the trial centerin one of the six Swedish health care regions. The patientswere assigned either to one week of preoperative irradiation,followed by surgery within the next week (radiotherapy-plus-surgerygroup), or to surgery with no additional radiotherapy (surgery-alonegroup).
Sample Size
In order to detect a reduction in the rate of local recurrencefrom 20 percent to 10 percent with 90 percent probability anda 5 percent significance level, we calculated that a total of475 patients had to be recruited. To detect an increase in postoperativemortality from 2 percent to 5 percent (again with 90 percentprobability and a 5 percent significance level), we needed torecruit 750 patients. To show an increase of 10 percentage pointsin survival (from 50 percent to 60 percent) after five yearswith 80 percent probability and a 5 percent significance level,750 curatively resected patients had to be recruited. Assuminga 10 percent dropout rate and assuming that approximately 20percent of the patients would be found to have metastatic diseaseat the time of surgery or would have a noncurative local resection,we had to enroll at least 1100 patients.
Patients
Between March 1987 and February 1990, we recruited patientswith resectable rectal carcinoma for whom abdominal surgerywas planned. Patients were eligible for the trial if they wereless than 80 years old, had a histopathologically proved adenocarcinomasituated below the promontory, as shown on a lateral projectionon barium enema, and gave informed consent for their participation.The protocol was approved by the regional ethics committees.
The criteria for exclusion were a locally nonresectable tumor;a plan to perform only local excision; known metastatic disease;previous radiotherapy to the pelvis; and other malignant disease(except squamous-cell carcinoma of the skin).
Of 1168 patients from 70 hospitals throughout Sweden who wererandomly assigned to treatment groups, 908 (78 percent; 454in each group) were treated with curative intent (Table 1).The patients' characteristics are described in the first reportfrom this trial.17 There is some overlap between the currentSwedish Rectal Cancer Trial and the so-called Stockholm II trial,18in that 316 patients who were enrolled in Stockholm from March1987 through February 1990 are also included in the currenttrial, whereas the patients enrolled after February 1990 inStockholm (238 patients) are not included in this analysis.
The clinical target volume, estimated according to the InternationalCommission on Radiation Units and Measurements report 50 (ICRU50), included the anal canal, the primary tumor, the mesorectaland presacral lymph nodes, the lymph nodes along the internaliliac vessels, the lumbar lymph nodes up to the level of theupper border of the fifth lumbar vertebra, and the lymph nodesat the obturator foramina. The plan was to deliver treatmentwith three beams with the patient in a prone position, as previouslydescribed,19 or with a four-beam "box" technique with the patientlying either supine or prone. Shielding of tissues not at riskof containing tumor cells was stipulated in the protocol.20
The protocol called for the delivery of 25 Gy in five fractionswith 5 to 16 megavoltage photons in one week. The dose was definedas that delivered at the intersection of the central axes ofthe three or four beams. This radiation schedule was designedto correspond approximately to a dose of 45 Gy given with conventionalfractionation (i.e., 2 Gy daily five days a week). Originally,the cumulative-radiation-effect (CRE) formula of Kirk et al.,21with corrections for late effects as described by Turesson andNotter,22 was used to estimate short-term and late effects ofdifferent radiation schemes. According to the original CRE concept,this treatment corresponds approximately to a total dose of42 Gy when given in fractions of 2 Gy five times a week. Withcorrections for late effects,22 the corresponding dose is approximately48 Gy. Using the linear–quadratic time model (LQ formula23),a dose of five fractions of 5 Gy each also corresponds to approximately42 to 50 Gy in 2-Gy fractions. Uncertainties about the precisecorrespondence remain, however, because of insufficient knowledgeof the size of the coefficients of the LQ formula for varioustumors and normal tissues.14,20
Surgery and Histopathological Analysis
Anterior resection or abdominoperineal excision was to be performedwithin one week after the completion of radiotherapy. Surgerywas considered locally curative if both the surgeon and thehistopathologist considered the margins of the resected tissueto be free of tumor, even if the bowel was perforated duringsurgery. The locally curative nature of surgery was definedas uncertain when either the surgeon or the pathologist reporteda questionable margin. In all other cases, the treatment wasconsidered not locally curative.
The resected specimens were examined by a pathologist in theregion where the center was located, who classified the tumoraccording to the original staging system of Dukes and Bussey.24When the rate of local recurrence was calculated in relationto tumor stage, the local Dukes' stage was used even when distantmetastases were known to exist. The pathologist also classifiedthe resection as locally curative, of uncertain curativeness,or not locally curative. The treatment was considered curativeif the resection was locally curative and no distant metastaseswere found during surgery.
Follow-Up
A clinical evaluation twice a year during the first five yearsafter surgery was stipulated in the protocol. Any clinicallydetectable tumor, whether morphologically verified or not, withinthe dorsal parts of the pelvis, including the urinary bladder,was considered a local recurrence. Laboratory tests, imaging,and biochemical tests were performed only if a local or distantrecurrence was suspected.
All case-record forms were checked by an independent observeragainst the clinical records during an audit in 1995. The causesof death of all patients who died were checked against the NationalCauses of Death Registry by computerized linkage. Living patientshad been followed up for a median of 75 months (range, 60 to96 months) as of March 1995.
Statistical Analysis
The significance of differences in proportions was calculatedwith the chi-square test, and that of differences between meanswith Student's t-test. P values of less than 0.05 were consideredto indicate statistical significance. Analyses of postoperativemortality and overall survival were based on all eligible patients(Table 1), whereas rates of postoperative morbidity and localrecurrence were based only on those who underwent resection.All comparisons between the treatment groups were made on theintention-to-treat principle. Survival and cumulative incidencewere estimated with actuarial methods. Distributions of factorswere analyzed with the log-rank test. A multivariate analysisof survival according to assigned treatment was performed withuse of the Cox proportional-hazards regression model, with boththe assigned treatment and the Dukes' stage included as independentvariables.
Before the trial started, it was stipulated that postoperativemortality and morbidity should be reported when the last patienthad been enrolled. Rates of local recurrence were to be analyzedafter two and five years of follow-up, and survival after aminimum of five years.
Results
Treatment and Postoperative Mortality
Of the 573 eligible patients who were randomly assigned to receivepreoperative radiotherapy, 555 (97 percent) received up to 25Gy of irradiation; no patient in the surgery-alone group receivedpreoperative radiotherapy. In 3 percent of the patients in bothgroups, the tumor was not resected, because it either was unresectableor was found to be metastatic at surgery (Table 1). Similarproportions in the two groups underwent surgery classified asnoncurative (Table 1). In-hospital mortality was 4 percent (22of 573 patients) in the radiotherapy-plus-surgery group and3 percent (15 of 574) in the surgery-alone group (P = 0.3).However, in the group of patients irradiated with two beams,in-hospital mortality was considerably higher (15 percent [7of 48 patients]) than in those irradiated as stipulated in theprotocol with three or four beams (3 percent [13 of 507], P<0.001).The distribution of the Dukes' stages in two groups is shownin Table 2 and described in detail in our first report.17
Table 2. Rates of Local Recurrence According to Dukes' Stage and Surgical Outcome among Patients with Resected Tumors Assigned to Radiotherapy plus Surgery or Surgery Alone.
Rates of Local Recurrence
After follow-up for a minimum of five years, the local-recurrencerates were significantly lower after combined radiotherapy andsurgery than after surgery alone in all groups of patients (Table 2).In the irradiated group, 11 percent (63 of 553 patients)had a local recurrence, as compared with 27 percent (150 of557) in the group undergoing surgery alone (P<0.001). Thecorresponding figures were 9 percent (41 of 454 patients) and23 percent (106 of 454) among the curatively treated patients(P<0.001). As shown in Table 2, a significant reduction inthe rate of local recurrence was found among patients with allthree Dukes' stages who underwent preoperative radiotherapy.Figure 1 shows the proportion of local failures observed afterdifferent amounts of follow-up. The reduction in the rate oflocal recurrence with radiotherapy was 58 percent (95 percentconfidence interval, 46 to 69 percent). The same reduction inthe rate of local recurrence with the addition of radiotherapywas also noted after different surgical procedures (Table 3).
Table 3. Rates of Local Recurrence According to Surgical Procedure among Patients Assigned to Radiotherapy plus Surgery or Surgery Alone.
Overall Rates of Recurrence
At follow-up, 28 percent of the curatively treated patients(125 of 454) in the radiotherapy-plus-surgery group had signsof recurrent disease, as compared with 38 percent (171 of 454)in the surgery-alone group (P<0.001). In the radiotherapy-plus-surgerygroup, 22 patients (5 percent) had only a local recurrence,and 84 (19 percent) had only distant metastases. The correspondingfigures in the surgery-alone group were 59 patients (13 percent)and 65 patients (14 percent), respectively. Both local and distantrecurrences were seen in 19 patients (4 percent) in the radiotherapy-plus-surgerygroup and in 47 patients (10 percent) in the surgery-alone group.
Survival
Both overall survival in all patients (Figure 2) and cancer-specificsurvival (Figure 3) among patients in whom curative surgerywas performed were significantly higher in the radiotherapy-plus-surgerygroup than in the group treated with surgery alone. The relativehazard of death from all causes in the radiotherapy-plus-surgerygroup was 0.79 (95 percent confidence interval, 0.66 to 0.92),and that of death due to cancer was 0.69 (95 percent confidenceinterval, 0.55 to 0.83). Overall five-year survival rates inthese two groups were 58 percent (95 percent confidence interval,54 to 62 percent) and 48 percent (95 percent confidence interval,44 to 52 percent), respectively (P = 0.004); radiotherapy wasthus associated with an increase of 21 percent (95 percent confidenceinterval, 8 to 34 percent) in overall survival.
Figure 3. Cancer-Specific Survival among All Patients Undergoing Curative Operations, According to Dukes' Stage and Treatment Assignment.
The bars indicate 95 percent confidence limits.
As shown in Table 2, more patients had a tumor in Dukes' stageA or B in the radiotherapy-plus-surgery group than in the surgery-alonegroup, a statistically significant difference (P = 0.008), whichis most likely due to a "down-staging" effect of preoperativeirradiation.17 To test whether the survival difference persistedafter adjustment for the imbalance in Dukes' stage — thatis, whether it was due to chance — we performed a Coxregression analysis including age, sex, Dukes' stage, and treatmentgroup as variables. In this analysis the relative hazard ofdeath from all causes changed only marginally, to 0.81 (95 percentconfidence interval, 0.67 to 0.94).
Discussion
We designed this trial to detect even a small but clinicallyrelevant survival benefit associated with the use of preoperativeradiotherapy in patients with resectable rectal cancer. We foundthat preoperative radiotherapy not only reduced the rate oflocal recurrences but also improved survival. Moreover, thesurvival benefit, 21 percent (95 percent confidence interval,8 to 34 percent), is of the same magnitude as that reportedby three North American trials of postoperative chemotherapy8or chemoradiotherapy9,10 in rectal cancer and is not significantlydifferent from that obtained with chemotherapy alone in patientswith Dukes' stage C colon cancer.25,26
The results of randomized trials worldwide of adjuvant radiotherapyfor rectal cancer indicate that preoperative radiotherapy ismore effective than postoperative radiation in reducing ratesof local failure.14,27 If the dose of radiation is moderatelyhigh, the reduction is at least 50 percent,1,2,4,6 as we alsofound. A reduction of this magnitude has not been found withlower preoperative doses3,5,28,29 or with even higher dosesdelivered postoperatively.7,8,9,10 Only one trial has comparedpreoperative and postoperative radiotherapy; the patients givenpreoperative radiotherapy received the same dose as those inour study.11 The patients who were treated postoperatively (onlythose in this group with tumors in Dukes' stage B or C underwentradiotherapy) received the highest dose used in an adjuvantsetting (60 Gy given over seven to eight weeks). Nevertheless,the preoperatively irradiated group had a significantly lowerrate of local recurrence (12 percent vs. 25 percent, P = 0.02).11,30
Concern has been expressed about the short- and long-term toxiceffects of high fractional doses of radiation.31 Doses higherthan 1.8 to 2.0 Gy per fraction, such as the 5-Gy fraction administeredin this and other trials,2,4,6 may lower the therapeutic ratio,particularly with respect to late toxic effects.31 Higher fractionaldoses imply shorter treatment periods and thus have practicaland economic advantages. The tumor-cell–killing effectof a dose of 25 Gy in one week (5 Gy daily for five days) correspondsapproximately to that of 42 to 50 Gy (2 Gy daily for five daysa week) over four to five weeks according to older conceptssuch as the CRE formula21 used in our study, the nominal standarddose,32 and the possibly more accurate LQ formula.23
We stress the importance of the irradiation technique, whichmust prevent unnecessary irradiation of tissues outside thetumor-containing areas. Our results and those of the Uppsalatrial11 show that five doses of 5 Gy each can be given preoperativelyto patients younger than 80 years without any significant increasein the number of complications in the immediate postoperativeperiod. The toxicity associated with a large radiation volumewas our chief reason for undertaking this study. Two beams cannotspare surrounding tissues to the same extent as three or fourbeams.20 Increased postoperative mortality, mainly among elderlypatients, was found in both the Stockholm–Malmö trial,6in which five fractional doses of 5 Gy each were also given,but with two beams extending above L2, and the British ImperialCancer Research Fund trial,2 in which three 5-Gy fractions weregiven with anterior–posterior beams to the entire pelviccavity. In another British trial, by the Northwest Region RectalCancer Group, four 5-Gy fractions were given with a rotationalthree-field wedge technique without any increase in postoperativemortality, further emphasizing the importance of the radiationtechnique.4
It is too early to evaluate the late adverse effects of theshort-term, high-dose preoperative radiotherapy protocol usedin this trial. A preliminary analysis of responses to a questionnaireabout anal function sent to all recurrence-free patients whohad a sphincter-saving procedure and were alive in 1996 (atleast five years after treatment) indicates that patients whounderwent irradiation have more problems with the number ofbowel movements, incontinence, urgency, and soiling than thosewho were assigned to surgery alone. However, their quality oflife is good and is not significantly different from that ofthe patients who had surgery alone (unpublished data). To minimizedisturbance of bowel function, the routine inclusion of theanal canal in the irradiated volume in proximal rectal tumors,as was standard in our trial, should probably be avoided. Analfunction after postoperative chemoradiotherapy has not beenstudied prospectively, but recent data suggest a worse outcomeafter postoperative than after preoperative treatment.33,34
Prospective follow-up over a 10-year period (still a ratherlimited period) in the Uppsala trial (in which five fractionsof 5 Gy each were delivered with three beams, with the upperlevel of the irradiated field at mid-L3) showed no increasedrisk of late adverse effects.28 The projected 10-year rate ofsmall-bowel obstruction was 5 percent among patients irradiatedpreoperatively, 6 percent among nonirradiated patients, and11 percent among those who received postoperative irradiation(30 fractions of 2 Gy each). The number of patients followedfor more than 10 years was small, however. The Stockholm–Malmötrial, in which the radiation dose was the same but the irradiatedvolume was considerably larger (upper level above L2 with twobeams), found an increase in thromboembolic events, femoral-neckand pelvic fractures, delayed perineal wound healing, and intestinalobstruction.18 In that study, pelvic fractures occurred onlyamong the patients treated in Stockholm, perhaps because thestipulated shielding was not used routinely in Stockholm. Inthe Stockholm II trial, which partly overlaps with our trial,there was a significantly increased rate of hospitalizationfor delayed perineal wound healing, but not for other complications.18
As compared with the group treated with surgery alone, therewere significantly more patients in Dukes' stage A and fewerpatients in Dukes' stage C in the group given preoperative radiotherapy(P = 0.008). This is most likely due to a down-staging effectof radiotherapy. Down-staging has also been observed in trialswith longer treatment periods and with an interval of severalweeks between the end of irradiation and surgery.1,3 Analysisof more than 1500 patients, including those in the present trialand the Uppsala trial,11 has shown that the tumors were significantlysmaller and the number of positive lymph nodes fewer in thepreoperatively irradiated group.35 This down-staging effectmay arouse concern on the part of physicians who routinely administerpostoperative chemotherapy to patients with Dukes' stage B orC tumors. However, when we analyzed survival separately amongpatients with the various Dukes' stages, we found improvementin all groups, although a statistically significant effect oftreatment was evident only in the group with tumors in Dukes'stage C (Figure 2). Moreover, this benefit persisted when theDukes' stage was taken into account in a Cox regression model.
Should all patients with a primary resectable rectal cancerreceive preoperative radiotherapy? Some surgeons claim theycan achieve very low rates of local recurrence and good survivalwithout radiotherapy, provided the surgical technique is optimal.36In this trial, the local-recurrence rate of 27 percent afterfive years of follow-up in the surgery-alone group is similarto the findings in all the other controlled trials on this topic,in which the local-recurrence rates in the surgery-alone groupshave varied from 20 percent to 40 percent (average, 28 percent).1,3,4,5,6,7,10,12,26,27These figures are unacceptably high in the light of the morbidityassociated with local failure. Optimal surgery, such as totalmesorectal excision for rectal cancer,36 might yield lower ratesof local recurrence than standard surgery, but no randomizedcomparison of these surgical methods has been reported. Perhapsa combination of radiotherapy and total mesorectal excisioncan improve the results even further.37
Of concern in all cases in which neoadjuvant treatment is usedis the overtreatment of patients with Dukes' stage A lesions,which can be recognized fairly easily and with reasonably highaccuracy by preoperative endorectal ultrasonography.38 However,in this trial the proportional reduction in the rates of localrecurrence was of the same magnitude among patients with tumorsin all Dukes' stages. This has also been reported from the Stockholm–Malmötrial.6 If surgery is optimal, preoperative ultrasonographycan be used to exclude patients from preoperative radiotherapy.Nevertheless, in patients with an anatomically very low tumor— especially in men in whom an abdominoperineal excisionis planned — preoperative radiotherapy should be consideredirrespective of tumor size, since such patients are at highrisk for local failure even if surgery is optimal.
Supported by a grant (1921-B91-08XBC) from the Swedish CancerSociety, by the Stockholm Cancer Society, and by the Jerzy andEva Cederbaum Minervafond.
We are indebted to Johan Bring at the Regional Oncological Centerin the Uppsala–Örebro health care region for statisticalassistance.
* Participating investigators are listed in the Appendix.
Source Information
Address reprint requests to Dr. Lars Påhlman at the Department of Surgery, Akademiska sjukhuset, University of Uppsala, S-751 85 Uppsala, Sweden. Dr. Påhlman and the Writing Committee assume responsibility for the overall content of the manuscript.
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Appendix
This study was performed in collaboration with the six RegionalOncological Centers in Sweden.
The study coordinators were L. Påhlman and B. Glimelius.The participating hospitals and clinicians were as follows:Stockholm–Gotland health care region — Karolinska:B. Cedermark, G. Lundell, C. Rubio, L.E. Rutqvist, N. Wilking,and Å. Öst; Huddinge: B. Brismar and S. Ewerth; Danderyd:L. Forsgren and C. Johansson; Södersjukhuset: I. Magnusson,P. Sundelin, C. Svensson, and B. Törnberg; Sabbatsberg:T. Theve; Nacka Sjukhus: G. Fenyö; Löwenströmska:S.O. Svensson; Ersta: S. Goldman and K. Molin; Visby: S. Bark,M. Sundblad; St. Göran: J. Dalén, C. Lindholmer,and B. Robertsson; Södertälje: U. Öhman; Norrtälje:S.-E. Nilsson; Uppsala–Örebro health care region— Akademiska: M. Dahlberg, B. Glimelius, W. Graf, G. Jansson-Frykholm,G. Lindmark, and L. Påhlman; Samariterhemmet: M. Westman;Enköping: H. Liljeholm; Falun: O. Bendtsen, U. Ljungquist,and A. Nihlberg; Mora: R. Heuman; Ludvika: T. Lorentz; Avesta:A. Bisgaard-Pedersen; Gävle: S. Bergström, M. Krog,and T. Tuvesson; Sandviken: P. Edman; Söderhamn: C. Lindström;Bollnäs: B. Sandhammar; Hudiksvall: G. Tydén; Karlstad:L. Bergman, L.-K. Enander, and I. Underskog; Säffle: H.Sellström; Kristinehamn: P. Armatys; Arvika: P. Moell;Eskilstuna: R. Hellberg and B. Stenstam; Kullbergska: G. Dafnis;Nyköping: H. Höjer; Linköping health care region— Linköping: L. Baldetorp, T. Hatschek, and R. Sjödahl;Norrköping: G. Arbman; Motala: E. Nilsson; Finspång:V. Störgren-Fordell; Jönköping: A. Hugander andF. Lagerberg; Eksjö: G. Simert; Värnamo: R. Aubergde la Rüe; Västervik: Å. Aldman; Kalmar: O.Lannerstad; Oskarhamn: P. Gullstrand; Lund–Malmöhealth care region — Malmö: Å. Arwidi, M. Bohe,G. Ekelund, H. Jiborn, and T. Landberg; Lund: S. Graffman, O.Jansson, and B. Jeppson; Landskrona: R. Sörbris; Trelleborg:E. Ohlsson; Ystad: S. Lenninger; Hässleholm: K. Halldén;Halmstad: C. Norryd and S. Adamsen; Göteborg health careregion — Sahlgrenska: R. Hultborn; Östra: S. Nilsson;Uddevalla: O. Magnusson and H.-E. Söderberg; Kungälv:B. Lindberg and E. Tveit; Borås: R. Jansson and J.H. Svensson;Alingsås: Å. Gustafsson; Trollhättan: B. Almskogand H. Salander; Skövde: D. Holmlund; Lidköping: S.Filipsson; Falköping: R. Laino; Umeå health careregion — Umeå: L. Athlin and N.-O. Bengtsson; Skellefteå:G. Broman; Boden: G. Lundegård; Luleå: S. Dedorson;Gällivare: G. Henriksson; Piteå: A. Nordahl; Kalix:G. Ryd; Östersund: G. Edlund; Sundsvall: J.-O. Svensson;Örnsköldsvik: J. Rutegård; Härnösand:M. Fagerberg; Sollefteå: K. Edin; Executive Committee:B. Cedermark, B. Glimelius, I. Magnusson, L. Påhlman,L.E. Rutqvist, T. Theve, and N. Wilking; Writing Committee:B. Cedermark, M. Dahlberg, B. Glimelius, L. Påhlman, L.E.Rutqvist, and N. Wilking.
Radiotherapy for Rectal Cancer
Lavery I. C., Fazio V. W., Lopez-Kostner F., Vikram B., Heriot A. G., Cornes P., Glees J. P., Kumar D., Påhlman L., Glimelius B., The Swedish Rectal Cancer Trial Group
Extract |
Full Text
N Engl J Med 1997;
337:346-348, Jul 31, 1997.
Correspondence
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A correction has been published: N Engl J Med 1997;336(21):1539.
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