retrospective analysis of concomitant cisplatin during...

Retrospective Analysis of Concomitant Cisplatin DuringRadiation in Patients Aged 55 Years or Older for

Treatment of Advanced Cervical CancerA Gynecologic Oncology Group Study

Charles Kunos, MD, PhD,* Chunqiao Tian, PhD,Þ Steven Waggoner, MD,þ Peter G. Rose, MD,§and Rachelle Lanciano, MD||

Hypothesis: Patients with stages II to IVa cervical cancer aged 55 years or older werecompared with patients younger than 55 years who received weekly cisplatin during pelvicradiation for differences in chemoradiation administration, toxicity, and outcome.Methods: Retrospective review included patients enrolled on Gynecologic OncologyGroup trial Nos. 120 and 165 (n = 335) who received weekly cisplatin (40 mg/m2) duringpelvic irradiation (40.8Y50.1 Gy) followed by intracavitary brachytherapy (30Y40 Gy).Results: For all 335 patients, 53% completed 6 cycles of chemotherapy during radiationwith no observed difference in frequency among patients younger than 55 years or 55 yearsor older (P = 0.616). Excess hematological but not genitourinary toxicity was seen inpatients 55 years or older. At 5 years, 56% of patients younger than 55 years were predictedto be alive and disease-free compared with 55% of those aged 55 years or older (P = 0.629).A 5-year survival was 60% in patients younger than 55 years as compared with 56% inpatients aged 55 years or older (P = 0.265).Conclusions: Patients aged 55 years or older with locally advanced cervical cancer un-dergoing concurrent weekly cisplatin with pelvic radiation on cooperative group clinicaltrials achieve similar progression-free and overall survivals as younger patients. Disparitywas not observed in the seriousness or frequency of treatment-related sequelae.

Key Words: Cervical cancer, Chemoradiation, Elderly

Received April 7, 2009, and in revised form May 19, 2009.Accepted for publication June 16, 2009.

(Int J Gynecol Cancer 2009;19: 1258Y1263)

*Department of Radiation Oncology, Case Comprehensive Cancer Centerand University Hospitals of Cleveland Case Medical Center, Cleveland,Ohio; †Gynecologic Oncology Group Statistical and Data Center, RoswellPark Cancer Institute, Buffalo, NY; ‡Department of Obstetrics and Gyne-cology, Division of Gynecologic Oncology, Case Comprehensive CancerCenter and University Hospitals of Cleveland Case Medical Center;§Department of Obstetrics and Gynecology, Division of Gynecologic On-cology, Case Comprehensive Cancer Center and The Cleveland Clinic,Cleveland, OH; and ||Department of Radiation Oncology, Delaware CountyMemorial Hospital, Drexel Hill, PA.Address correspondence and reprint requests to Charles Kunos, MD, PhD,

Department of Radiation Oncology, University Hospitals Case MedicalCenter, 11100 Euclid Ave, LTR 6068, Cleveland, Ohio 44106. E-mail:[email protected].

This study was supported in part by a grant (K12 CA076917) to C.K. fromthe National Institutes of Health and the Case Comprehensive CancerCenter and also by National Cancer Institute grants to the GynecologicOncology Group Administrative Office (CA 27469) and the GynecologicOncology Group Statistical Office (CA 37517).

The following member institutions participated in this study: University ofAlabama at Birmingham, Oregon Health Sciences University, DukeUniversity Medical Center, Abington Memorial Hospital, University of

Rochester Medical Center, Walter Reed Army Medical Center, WayneState University, University of Minnesota Medical School, EmoryUniversity Clinic, University of Southern California at Los Angeles,University of Mississippi Medical Center, ColoradoGynecologic Oncology Group, PC, University of California at LosAngeles, University of Washington, University of PennsylvaniaCancer Center, University of Miami School of Medicine, Milton S.Hershey Medical Center, Georgetown University Hospital,University of Cincinnati, University of North Carolina School ofMedicine, University of Iowa Hospitals and Clinics, University ofTexas Southwestern Medical Center at Dallas, Indiana UniversitySchool of Medicine, Wake Forest University School of Medicine, AlbanyMedical College, University of California Medical Center at Irvine,Tufts-New England Medical Center, Rush-Presbyterian-St Luke’sMedical Center, SUNY Downstate Medical Center, University ofKentucky, Eastern Virginia Medical School, The Cleveland ClinicFoundation, Johns Hopkins Oncology Center, State University of NewYork at Stony Brook, Eastern Pennsylvania GYN/ONC Center, PC,Cooper Hospital/University Medical Center, Columbus Cancer Council,University of Massachusetts Medical School, Fox Chase Cancer Center,Medical University of South Carolina, Women’s Cancer Center,University of Oklahoma, University of Virginia Health Sciences Center,University of Chicago, University of Arizona Health Science Center,Tacoma General Hospital, Mayo Clinic, Case Western ReserveUniversity, Tampa Bay Cancer Consortium, and The New YorkHospital/Cornell Medical Center.

ORIGINAL ARTICLE

1258 International Journal of Gynecological Cancer & Volume 19, Number 7, October 2009

Copyright * 2009 by IGCS and ESGOISSN: 1048-891XDOI: 10.1111/IGC.0b013e3181b33ace

Copyright @ 2009 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.

Cervical carcinoma ranks second among malignancies in womenworldwide, accounting for nearly 190,000 deaths annually.1Age at diagnosis for new cases of cervical carcinoma has beenobserved to follow a bimodal distribution, with peak ages at 30 to39 years and 60 to 69 years. Age at diagnosis has been identifiedas a risk factor for cancer relapse and death after chemoradiation forlocally advanced stages II to IVa cervical cancer. A prior GynecologicOncology Group (GOG) multivariate study of nonYcisplatin-containing chemoradiation trials showed that older patient age wassignificantly associated with less frequent cervical cancer relapseor cancer-related death,2 yet contemporary cisplatin-containingchemoradiation trials no longer identify patient age influencingrisk of relapse or survival after adjusting for cofactors.3Y8 Never-theless, population-based studies have shown an increased dispar-ity in cervical cancer incidence and mortality among patients aged55 years or older.1,9

The US Surveillance, Epidemiology, and End-Results (SEER)cancer registries reported a 35% incidence of cervical cancer but55% cervical cancerYrelated mortality for patients aged 55 years orolder (1998Y2002).10 Explanations for the disparity between cervicalcancer incidence and mortality are lacking. Perhaps, patient che-motherapy administration during radiation is not being realized asrecommended by cooperative group clinical trials.3Y8 An earliernational Patterns of Care Study evaluating practice patterns between1996 and 1999 showed that 25% of patients 60 years or olderunderwent chemoradiation for cervical cancer as compared with48% among patients aged 40 years or younger (P = 0.02).11 Be-tween 1998 and 2002, SEER-Medicare data show increased che-moradiation administration among women aged 55 years or older;however, only 43% aged 55 years or older received concurrentchemoradiation.9

Whether patients aged 55 years or older derive benefit fromchemoradiation treatment of cervical cancer remains relativelyunknown. This is, in part, because of limited numbers of patientsaged 55 years or older enrolled in clinical chemoradiation studies ofadvanced cervical cancer. Beliefs that patients aged 55 years or oldertolerate chemoradiation more poorly may also lead to a lack ofclinical outcome benefit for chemoradiation.12 In the case of con-current radiosensitizing cisplatin, perceived and actual hematolog-ical, genitourinary, and gastrointestinal sequelae often lead to thepractice of withholding chemoradiation for treatment of cervicalcancer in older patients.13,14

The purpose of this retrospective study was to evaluate che-moradiation administration, toxicity, and outcome of patients withcervical cancer aged 55 years or older as compared with patientsyounger than 55 years treated on GOG protocol Nos. 120 and 165.

METHODSDetailed methodology for clinical trial GOG Nos. 120 and

165 have been published previously.3,4 Briefly, patients had un-treated stage IIB, III, or IVA invasive squamous, adenosquamous,or adenocarcinoma of the cervix. To establish clinical stage,patients must have undergone complete physical examination, pel-vic examination, and chest radiograph. Surgical staging was man-datory for GOG No. 120 but optional for GOG No. 165, with 18%of GOG No. 165 study patients undergoing surgical staging.3,4

Patients with disease outside the pelvis, those with surgically orradiographically confirmed para-aortic node metastasis or those notcandidates for radiation, were ineligible. Institutional review boardapproval among participating institutions was obtained for clinicaltrial GOG protocol Nos. 120 and 165. Written informed consentconsistent with institutional, state, and federal regulations wasobtained before entry on the study and randomization.

ChemotherapyGynecologic Oncology Group Nos. 120 (n = 176) and 165

(n = 159) included patients randomly assigned to weekly cisplatinchemotherapy (40 mg/m2) for 4 hours before radiation therapy ondays 1, 8, 15, 22, 29, and 36. Cisplatin chemotherapy was dis-continued for leukopenia (GOG 0120 G 2500 or GOG 0165 G 3000per cubic millimeter) or thrombocytopenia (GOG 0120 G 50,000 orGOG 0165 G 100,000 per cubic millimeter) and resumed after re-solution. For subsequent cycles, cisplatin chemotherapy was dis-continued for neurotoxicity grade 3 and higher or a creatinine levelof more than 2 mg/dL. Gynecologic Oncology Group Nos. 120and 165 did not specify growth factor administration.

RadiationFor GOG No. 120, anterior-posterior and posterior-anterior

or 4-field box technique pelvic radiation was delivered in 1.7-Gyfractions using 4-MV photons or higher to doses ranging from40.8 Gy for patients with stage II to 51.0 Gy for patients with stageIII/IVA. In GOG No. 165, 4-field box pelvic radiation was deliveredin 1.8-Gy fractions using 4-MV photons or higher to a dose of45.0 Gy. In general, the 4-field box techniques used an upper marginof the L5 vertebra and a lower margin of the midportion of theobturator foramen or the lowest extent of disease with a 3-cm marginfor anterior and posterior radiation fields. Laterally, the anterior andposterior radiation fields extended 1.5 to 2 cm beyond the pelvicbrim. For right and left lateral radiation fields, the anterior borderwas the pubic symphysis, and the posterior border was the spacebetween the S2 and S3 vertebrae. The superior and inferior marginsfor lateral radiation fields were the same as the anterior and posteriorradiation fields.

Intracavitary lowYdose rate brachytherapy followed externalbeam radiation 1 to 3 weeks later. One or 2 applications were allowed.LowYdose rate brachytherapy doses were 40.0 Gy for patients withstage II and 30.0 Gy for patients with stage III/IVA on GOG protocolNo. 120 and 40.0 Gy for all stages on GOG No. 165, prescribed toradiation prescription point A. If intracavitary brachytherapy couldnot be delivered, additional external beam radiation to a dose of61.2 Gywas done. Interstitial brachytherapy was not allowed on GOGNo. 120 or 165, but highYdose rate brachytherapy was allowed onGOG No. 165. For GOG No. 165, highYdose rate brachytherapyconsisted of 5 fractions of 6.0 Gy (total dose, 30.0 Gy) started thefourthweekof external beam radiationwith at least 1 fraction perweek.In both studies, total irradiation time was to be less than 10 weeks.Radiotherapy was withheld for grade 3 or 4 leukopenia and up to1 week for gastrointestinal or genitourinary radiation-related toxicity.

Statistical AnalysisAge groups were dichotomized at 55 years owing to the

disparity of cervical cancer incidence and mortality apparent inSEER cancer registries10 and then at 70 years owing to an apparentdecrease in odds of chemotherapy use during radiation amongpatients with cervical cancer in the US SEER-Medicare cancerregistry between 1998 and 2003.9 Age was dichotomized tofacilitate comparison to 1998Y2003 US SEER-Medicare data thatreflect cancer health service delivery to a highly skewed populationof women aged 55 years or older.9 Several parameters of che-motherapy were evaluated in relation to age groups. Relative dose(RD) was the ratio of actual to expected dose of cisplatin in standardchemotherapy (40 mg/m2 � 6 cycles). Relative time (RT) was de-fined as the ratio of actual to expected duration of chemotherapy(6 weeks). Relative dose intensity (RDI) was defined as the ratio ofRD to RT. A ratio lesser than 1.0 indicated patients received lessintensity of chemotherapy than planned. Treatment completion wasdefined as completing 6 cycles of chemotherapy because this wasthe proposed number of cycles in the 2 GOG studies. Treatment

International Journal of Gynecological Cancer & Volume 19, Number 7, October 2009Chemoradiation in Women

Aged 55 Years or Older

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toxicities were graded as defined in previous clinical reports.3,4

Progression-free survival (PFS) was calculated from date of patientenrollment to the date of progression or recurrence of disease, death,or most recent follow-up visit. Overall survival (OS) was calculatedfrom the date of patient enrollment to the date of death or lastcontact.

The mean RD, RT, and RDI between patients younger than55 years and patients aged 55 years or older were compared usingStudent t test. The number of treatment cycles, cause of treatmentincompletion, and toxicity were compared by Pearson W2 test. Thefactors associated with treatment incompletion were identifiedusing a logistic regression model. The cumulative probability ofPFS or OS was estimated by Kaplan-Meier procedure, and the log-rank test was used to compare the difference of the distributionbetween the 2 groups. All statistical analyses were 2 tailed (> = 0.05)and were performed using Statistical Analysis System software(SAS version 9.1; SAS Inc, Cary, NC).

RESULTSOf 335 patients included for this analysis, median age was 49

years (range, 20Y80 years). Two hundred thirty-two patients were

younger than 55 years, and 103 patients were 55 years or older.There were 13 elderly patients (Q70 years) included in this analysis.There were no significant differences between the 2 age groups inthe distributions of race, GOG performance status, clinical stage,tumor grade, tumor histologic diagnosis, or parametrial involve-ment. However, larger tumors (P = 0.003) or pelvic lymph nodes

TABLE 1. Patient characteristics by age group

CharacteristicG55 yr

(n = 232), %Q55 yr

(n = 103), % P

RaceWhite 56.5 66.0 0.083Black 25.4 19.4Other 18.1 14.6

GOG performance status0 71.6 65.1 0.2331 or 2 28.5 35.0

StageII 62.9 60.2 0.634III/IV 37.1 39.8

Tumor grade1 9.1 5.8 0.5972 59.1 60.23 or not graded 31.9 34.0

Histologic diagnosisSquamous 87.9 85.4 0.529Others 12.1 14.6

Tumor size, cmG5 48.7 66.0 0.003Q5 51.3 34.0

Parametrial involvementUnilateral 56.9 61.2 0.465Bilateral 43.1 38.8

Pelvic nodePositive 16.4 6.8 0.018Negative/not done 83.6 93.2

Protocol treatmentGOG 120 53.5 50.5GOG 165 46.6 49.5

Pearson W2 method used to compare the difference in proportion between2 groups.

TABLE 2. Treatment parameters by age group

TreatmentParameter

G55 yr(n = 232)

Q55 yr(n = 103) P

RD*Mean (SD) 0.85 (0.17) 0.84 (0.20) 0.830†Median(25thY75th Pct)

0.87 (0.79Y0.99) 0.88 (0.81Y0.97)

RT‡Mean (SD) 1.00 (0.27) 1.09 (0.79) 0.251†Median(25thY75th Pct)

1.00 (0.83Y1.14) 1.00 (0.83Y1.24)

RDI§Mean (SD) 0.87 (0.15) 0.86 (0.18) 0.547†Median(25thY75th Pct)

0.92 (0.79Y0.99) 0.94 (0.75Y0.98)

No. treatmentcycles, %0 0.0 1.01 0.9 1.92 0.0 1.93 6.5 1.94 8.6 11.75 30.6 31.16 53.5 50.5 0.616||

*Ratio of actual to expected dose of chemotherapy.†Student t test use to compare the difference between 2 groups.‡Ratio of actual to expected duration of chemotherapy.§Relative dose/RT.||Pearson W2 used to compare the proportion of completion (53.5% vs

50.5%).

TABLE 3. Treatment-related adverse effects by age group

Adverse EffectG55 Yr

(n = 232), %Q55 Yr

(n = 103), % P*

Grade 3 or 4 (selected)Leukopenia 22.0 32.0 0.050Thrombocytopenia 2.2 1.0 0.671Other hematological 12.1 21.4 0.028Gastrointestinal 18.1 19.4 0.775Genitourinary 6.5 1.9 0.082Neurological 1.7 1.0 1.000Cutaneous 2.6 50.5 1.000

Any grade 3 or 4 47.8 2.90.656

*Pearson W2 or Fisher exact method used to compare the difference inproportion between 2 groups.

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with metastasis (P = 0.018) were observed more commonly amongpatients younger than 55 years (Table 1).

Overall, 53% of patients completed 6 cycles of chemotherapyduring radiation. The mean RD, RT, and RDI were 0.85, 1.03, and0.87, respectively (Table 2). Patients younger than 55 years or 55years or older were equally likely to finish 6 cycles of chemotherapyduring radiation (54% vs 51%; P = 0.616), without differences inRD, RT, and RDI (Table 2). For the 13 elderly patients (Q70 years), 7(54%) completed 6 cycles of chemotherapy during radiation.

In this study population, 49% of patients reported at least 1grade 3 or 4 adverse effect without difference between age groupsyounger than 55 years and 55 years or older. Although thrombocy-topenia, genitourinary, and neurological and cutaneous toxicitieswere rare, a higher proportion of patients aged 55 years or olderexperienced leukopenia (32% vs 22%; P = 0.050) and otherhematological (21% vs 12%; P = 0.028) toxicities during chemor-adiation (Table 3). Nine (69%) of 13 patients aged 70 years or olderexperienced at least 1 grade 3 or 4 adverse effect.

After controlling for other clinical factors and treatmentprotocol (Table 4), patients aged 55 years or older were no more likely to stop cisplatin chemotherapy during radiation as compared

with patients younger than 55 years (odds ratio [OR], 1.16; 95%confidence interval [CI], 0.71Y1.89; P = 0.552). The only factorpotentially affecting treatment completion was race, as African-American patients had a greater frequency of not completing pre-scribed protocol therapy than white patients (OR, 2.13; 95% CI,1.22Y3.74; P = 0.029). Reasons describing why a patient did notcomplete prescribed protocol therapy were not encoded for theseclinical trials.

At the time of this report, 169 patients showed disease pro-gression, including 157 deaths. Median follow-up duration forpatients still alive was 94 months, with a maximum follow-up of169 months (25%Y75% quartile, 78Y123 months). At 5 years, 56%of patients younger than 55 years were predicted to be alive anddisease-free compared with 55% of those aged 55 years or older(Fig. 1). The distribution of PFS was essentially the same (log-ranktest: P = 0.629). There was also no significant difference in OSbetween the 2 groups (log-rank test: P = 0.265), with a 5-yearsurvival of 60% in patients younger than 55 years compared with56% in patients aged 55 years or older (Fig. 2).

DISCUSSIONThis report confirmed that in the cooperative group, clinical

trial setting, chemoradiation administration, toxicity, and outcome ofpatients with cervical cancer aged 55 years or older are similar to

FIGURE 1. Kaplan-Meier estimate of PFS for patients youngerthan 50 years and patients aged 50 years or older.

TABLE 4. Factors associated with treatment incompletion

Characteristic Incompletion, % OR (95% CI) P*

Age group, yr 0.552G55 46.6 ReferentQ55 49.5 1.16 (0.71Y1.89)

Race 0.029White 43.3 ReferentAfrican American 60.8 2.13 (1.22Y3.74)Other 45.2 1.09 (0.61Y1.96)

Performance status 0.3610 45.9 Referent1 or 2 51.0 1.27 (0.76Y2.11)

Stage 0.146II 50.5 ReferentIII/IV 42.5 0.70 (0.43Y1.13)

Histologic diagnosis 0.310Squamous 48.6 ReferentOthers 39.5 0.70 (0.36Y1.39)

Tumor grade 0.4061 44.4 Referent2 45.7 1.13 (0.49Y2.61)3 51.4 1.53 (0.64Y3.68)

Tumor size, cm 0.481e5 49.2 Referent95 45.5 0.85 (0.53Y1.34)

Parametrialinvolvement

0.580

Unilateral 49.2 ReferentBilateral 45.0 0.87 (0.54Y1.42)

Pelvic node 0.524Positive 48.3 ReferentNegative/not done 42.2 0.81 (0.41Y1.57)

*Odds ratio estimated by Logistic regression model, adjusted forcovariates and protocol. FIGURE 2. Kaplan-Meier estimate of OS for patients younger

than 50 years and patients aged 50 years or older.





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patients of younger age. Given that chemoradiation use for locallyadvanced cervical cancer has risen steadily because of publication of5 chemoradiation clinical trials, patients aged 55 years or older wereexpected to have similar risks of cancer-related relapse or death ascompared with patients younger than 55 years.4Y8 For given tumorand demographic factors for patients enrolled in GOG Nos. 120 and165, patients aged 55 years or older were just as likely to completeall recommended chemotherapy treatments during radiation aspatients of younger age.

Retrospective analyses of population-based cancer registrieshave not encoded detailed chemotherapy administration records.Unlike population-based cancer registry studies, this retrospectiveanalysis of 2 cooperative group clinical trials offered reliableabstraction of the exact regimen of chemotherapy administration,patient-specific chemotherapy dosage, and adverse effects oftreatment. In this study, ratios of actual delivered chemotherapydose to expected dose, actual to expected time of chemotherapydelivery, and RD to RT were determined for GOG protocols Nos.120 and 165. The observed RD, RT, and RDI were similar amongtreated patients regardless of age (Table 2), even among the limitednumber of patients aged 70 years or older. Certainly, this finding isopen to interpretive criticism. Not only patients participating inclinical trials are often highly motivated to complete protocolprescription therapy, but also physicians are highly motivated tohave their patients complete all protocol prescription therapy. Forinstance, in the 1998Y2002 SEER-Medicare population cervicalcancer registry, only 47% of patients aged 55 years or older treatedfor locally advanced cervical cancer with radiation received at least 5cycles of concomitant chemotherapy.9 A significant decreased oddsof radiation and chemotherapy administration in patients aged71 years or older was also observed.9 By comparison, 84% ofpatients younger than 55 years and 82% of patients aged 55 years orolder completed at least 5 cycles of chemotherapy in GOG protocolNos. 120 and 165. Perhaps, patient and physician motivations andpossibly overall ancillary treatment support provided by controlledcooperative group clinical trials accounts for the disparity inchemotherapy use during radiation administration among SEER-Medicare and GOG patient populations.

In previous retrospective analyses, it has been noted thatphysician bias, attributed to elderly patient moderate-to-severemedical comorbidity, adversely impacts allocation of primary andadjuvant therapies for patients with cancer.12,15Y17 In this report,there was not an overall excess incidence of treatment-related tox-icity in patients aged 55 years as compared with younger patients(Table 3). For patients aged 55 years or older, the proportion ofthose alive and free of disease was similar to younger patients, ata cost of an increased incidence of manageable grade 3 and higherhematological toxicity. Growth factors were not used in eitherGOG protocol Nos. 120 or 165 and, perhaps, with further study inthe 55-year or older patient population, could lessen hematologicaltoxicity. Genitourinary toxicity was not higher in patients aged55 years or older despite the more probable increased incidence ofimpaired renal function in these patients.

While treatment-related toxicity was not a barrier to finishingchemotherapy, there was a disparity in the proportion of African-American patients not completing prescribed chemotherapy duringradiation. Among African-American patients, there was not anidentifiable treatment-related factor or toxicity associated with notcompleting prescribed therapy. For GOG Nos. 120 and 165,compelling evidence explaining the observed disparity of treatmentcompletion was not identified in multivariate analyses.14 Radiationdose and brachytherapy technique were different in GOG Nos. 120and 165, but too few patients (21 enrolled on GOG 165 [6%] of the335 total studied here) underwent highYdose rate brachytherapy tocomment.3 Perhaps, one explanation could be found among

differences in poverty and education levels, as these factors havebeen associated with lower likelihoods of completing prescribedtherapy, which translates into poorer survival.18Y20 In populationstudies using SEER cancer incidence data, disparity between 5-yearsurvival rates were 7% between low and high poverty and 7%between low and high education census tracts.18 Among patientsstudied for this analysis, reliable proxy indicators of socioeconomicand educational statuses were not readily coded for analysis and,thus, cannot be commented upon as contributing factors to in-complete protocol treatment administration.

With a median follow-up of 94 months among survivors,patients aged 55 years or older were not more likely to relapse or dieof cervical cancer as compared with patients younger than 55 yearswhen radiosensitizing doses of cisplatin chemotherapy were ad-ministered. Within the cohorts aged 55 years or older and youngerthan 55 years of GOG Nos. 120 and 165, subpopulations do farebetter, as a nonlinear association between age and survival hasbeen observed with patients aged 51 to 60 years having a betterprognosis than those patients aged 40 years or younger.14 As such,substantial gains in PFS and OS observed for patients in thesecohorts perhaps may only be applicable when cisplatin chemother-apy is used. Concurrent weekly cisplatin with pelvic radiationsignificantly improves long-term PFS and OS as compared withradiation alone for patients with cervical cancer.4Y6 Whether otherradiosensitizing chemotherapeutic agents achieve these gainsremains unanswered. For patients aged 55 years or older who donot receive cisplatin chemotherapy owing to medical comorbidity orlack of administrative ability, other agents that can be safely andreliably given during radiation should be studied. The GOG andother large cooperative groups continue to refine the optimalregimen for chemoradiation in the treatment of patients with locallyadvanced cervical cancer.

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3. Lanciano R, Calkins A, Bundy BN, et al. Randomized comparisonof weekly cisplatin or protracted venous infusion of fluorouracil incombination with pelvic radiation in advanced cervix cancer: aGynecologic Oncology Group Study. J Clin Oncol. 2005;23:8289Y8295.

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5. Eifel PJ, Winter K, Morris M, et al. Pelvic irradiation with concurrentchemotherapy versus pelvic and para-aortic irradiation for high-riskcervical cancer: an update of radiation therapy oncology group trial(RTOG) 90-01. J Clin Oncol. 2004;22:872Y880.

6. Stehman FB, Ali S, Keys HM, et al. Radiation therapy with orwithout weekly cisplatin for bulky stage 1B cervical carcinoma:follow-up of a Gynecologic Oncology Group trial. Am J Obstet Gynecol.2007;197:503.e1Y6.

7. Whitney CW, Sause W, Bundy BN, et al. Randomized comparison offluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiationtherapy in stage IIB-IVA carcinoma of the cervix with negativepara-aortic lymph nodes: a Gynecologic Oncology Group Study. J ClinOncol. 1999;17:1339Y1348.

8. Peters WI, Liu P, Barrett R, et al. Concurrent chemotherapy andpelvic radiation therapy compared with pelvic radiation therapy aloneas adjuvant therapy after radical surgery in high-risk early-stage cancerof the cervix. J Clin Oncol. 2000;18:1606Y1613.

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10. National Cancer Institute Cancer Statistics Branch. SEER CancerStatistics Review 1975Y2002 Tables 1Y10 and 1Y12, 2005 (vol 2007).http://seer.cancer.gov/csr/1975_2002. Accessed April 1, 2009.

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15. Neugut AI, Fleischauer AT, Sundarajan V, et al. Use of adjuvantchemotherapy and radiation therapy for rectal cancer among theelderly: a population-based study. J Clin Oncol. 2002;20:2643Y2650.

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