Predictors of treatment failures during chemotherapy: A prospective study on 110 older cancer patients. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. Geriatric assessment is associated with completion of chemotherapy, toxicity, and survival in older adults with cancer. A prospective, longitudinal study of the functional status and quality of life of older patients with breast cancer receiving adjuvant chemotherapy. Predictors of tolerance to chemotherapy in older cancer patients: a prospective pilot study. Determining the relationship between toxicity and quality of life in an ovarian cancer chemotherapy clinical trial. Association between treatment toxicity and outcomes in oncology clinical trials. The toxicity gap: Do real-life patients get hospitalized more during chemotherapy compared to trial patients? The outcome of combined-modality therapy for stage III non-small-cell lung cancer in the elderly. Psychometric evaluation of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group—Neurotoxicity (Fact/GOG‐Ntx) questionnaire for patients receiving systemic chemotherapy Outcomes evaluation of a weekly nurse practitioner-managed symptom management clinic for patients with head and neck cancer treated with chemoradiotherapy. Reirradiation alternating with docetaxel and cisplatin in inoperable recurrence of head-and-neck cancer: a prospective phase I/II trial. Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. Evaluation of Viable Dynamic Treatment Regimes in a Sequentially Randomized Trial of Advanced Prostate Cancer Prospective, risk-adapted strategy of stereotactic body radiotherapy for early-stage non-small-cell lung cancer: results of a Phase II trial. Predictors of severe acute and late toxicities in patients with localized head-and-neck cancer treated with radiation therapy. Phase III multi-institutional trial of adjuvant chemotherapy with paclitaxel, estramustine, and oral etoposide combined with long-term androgen suppression therapy and radiotherapy versus long-term androgen suppression plus radiotherapy alone for high-risk prostate cancer: preliminary toxicity analy
Several instruments have been proposed to improve treatment decisions in elderly cancer patients , but evidence of their impact in clinical practice is limited . The aim of this study was to analyze the role of clinical and functional factors in predicting serious adverse events , including death , severe toxicity or treatment interruption , during chemotherapy in elderly cancer patients . The survey evaluated elderly with lung or colon or breast cancer treated with chemotherapy , followed by S. Giovanni Battista Hospital . We enrolled 110 consecutive patients older than 70 years of age with lung ( n=45 ) , colon ( n=50 ) and breast ( n=15 ) cancer between October 2004 and October 2005 . Overall , 73/110 patients ( 66.4 % ) experienced adverse events as death ( n=14 ) , grade s III and IV toxicity ( n=40 ) , or treatment interruption for other reasons ( n=19 ) . The variables with stronger predictivity were advanced stage , toxicity of treatment , level of comorbidity and Karnofsky performance status ( KPS ) . instrumental activities of daily living ( IADL ) index and age itself were not independent predictors . In conclusion our results confirm the need of a careful selection of elderly patients suitable for chemotherapy  , giving more weight to comorbidity and KPS scores than to age itself . The potential role of other functional evaluations need to be further assessed in r and omized controlled trials PURPOSE Older adults are vulnerable to chemotherapy toxicity ; however , there are limited data to identify those at risk . The goals of this study are to identify risk factors for chemotherapy toxicity in older adults and develop a risk stratification schema for chemotherapy toxicity . PATIENTS AND METHODS Patients age ≥ 65 years with cancer from seven institutions completed a prechemotherapy assessment  that captured sociodemographics , tumor/treatment variables , laboratory test results , and geriatric assessment variables ( function , comorbidity , cognition , psychological state , social activity/support , and nutritional status ) . Patients were followed through the chemotherapy course to capture grade 3 ( severe ) , grade 4 ( life-threatening or disabling ) , and grade 5 ( death ) as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events . RESULTS In total , 500 patients with a mean age of 73 years ( range , 65 to 91 years ) with stage I to IV lung ( 29 % ) , GI ( 27 % ) , gynecologic ( 17 % ) , breast ( 11 % ) , genitourinary ( 10 % ) , or other ( 6 % ) cancer joined this prospect i ve study . Grade 3 to 5 toxicity occurred in 53 % of the patients ( 39 % grade 3 , 12 % grade 4 , 2 % grade 5 ) . A predictive model for grade 3 to 5 toxicity was developed that consisted of geriatric assessment variables , laboratory test values , and patient , tumor , and treatment characteristics . A scoring system in which the median risk score was 7 ( range , 0 to 19 ) and risk stratification schema ( risk score : percent incidence of grade 3 to 5 toxicity ) identified older adults at low ( 0 to 5 points ; 30 % ) , intermediate ( 6 to 9 points ; 52 % ) , or high risk ( 10 to 19 points ; 83 % ) of chemotherapy toxicity ( P < .001 ) . CONCLUSION A risk stratification schema can establish the risk of chemotherapy toxicity in older adults . Geriatric assessment variables independently predicted the risk of toxicity OBJECTIVES Our purpose was to determine whether geriatric assessment s are associated with completion of a chemotherapy course , grade III/IV toxicity or survival in older adults with cancer . MATERIAL S AND METHODS In this prospect i ve cohort study , patients aged 65 years and older with colorectal , lung , or breast cancer or lymphoma completed a  brief geriatric assessment prior to chemotherapy . Endpoints included completion of the planned number of chemotherapy cycles , grade III/IV toxicity and survival . Multivariate logistic regression determined which factors were independently associated with completion of therapy , grade III/IV toxicity or death . RESULTS Sixty-five patients were enrolled in the study . The median age was 73 years ( range 65–89 ) .  Geriatric syndromes were common , including depression ( 21.5 % ) , dependence on others to carry out instrumental activities of daily living ( 38.5 % ) and activities of daily living ( 10.8 % ) , and comorbidities ( mild 47.7 % , moderate 20 % , severe 15.4 % ) . Of the 65 participants , 67.6%completed the planned number of chemotherapy cycles . Curative intent therapy [ OR 4.97 ( 95 % CI 1.21–18.81 ) ] , Eastern Cooperative Oncology Group ( ECOG ) performance status 2–3 [ OR 0.089 ( 0.015–0.53 ) ] and renal function [ OR 1.03 ( 1.00–1.06 ) per ml/min ] were significantly associated with therapy completion . Furthermore , 31.1 % experienced grade III/IV nonhematologic toxicity . Moderate to severe comorbidities significantly increased the risk of grade III/IV non-hematologic toxicity [ OR 6.13 ( 1.65–22.74 ) ] . Patients who received chemotherapy with curative intent had lower mortality [ HR 0.15 ( 0.06–0.42 ) ] , while patients who reported a fall in themonth prior to chemotherapy had an increased risk of death [ HR 3.20 ( 1.13–9.11 ) ] . CONCLUSIONS Geriatric assessment is associatedwith completion of a planned number of cycles of chemotherapy , grade III/IV non-hematologic toxicity , and mortality OBJECTIVES To examine the toxicity experienced by a cohort of older women receiving adjuvant chemotherapy for breast cancer and the longitudinal effect on their functional status and quality of life ( QOL ) . DESIGN A geriatric assessment measuring functional status , comorbidity , mood , nutritional status , and QOL was performed before chemotherapy , at the end of chemotherapy , and 6 months later . SETTING This prospect i ve longitudinal study was conducted at Memorial Sloan-Kettering Cancer Center , New York , New York . PARTICIPANTS Fifty patients aged 65 and older with Stage I to III breast cancer receiving any adjuvant chemotherapy ; 49 were evaluable . MEASUREMENTS The chemotherapy regimen and the toxicity to chemotherapy were recorded . A  geriatric assessment  was performed before the start of chemotherapy , on completion of chemotherapy , and 6 months after completion of chemotherapy .  QOL testing was performed at the same times . RESULTS Patients ( mean age 68 , range 65 - 84 ) received an anthracycline-based chemotherapy regimen ( n=15 ) or cyclophosphamide 600 mg/m2 intravenously ( i.v . ) , methotrexate 40 mg/m2 i.v . , 5-fluorouracil 600 mg/m2 i.v . every 3 weeks for eight cycles ( n=34 ) . Grade 3 or 4 toxicity occurred in 53 % ( n=26 ) , hematological toxicity in 27 % ( n=13 ) , and nonhematological toxicity in 31 % ( n=15 ) . Despite toxicity , there was no significant longitudinal change in functional status or QOL . CONCLUSION Despite toxicity from adjuvant chemotherapy , this cohort of relatively young older patients maintained their functional status and QOL from before chemotherapy to 6 months postchemotherapy . Subtle changes in higher-order functioning would require assessment using different geriatric assessment tools Few data are available to help predict which older cancer patient is at risk of developing chemotherapy-related toxicity . This study was a pilot for a project design ing a predictive risk score . Chemotherapy patients aged 70 years and older were prospect ively enrolled .  Chemotherapies were adjusted for their published toxicity . 60 patients were enrolled , 59 were evaluable . Mean dose-intensity was 90.3 % , range 33.3 - 129.0 % . 47 % of the patients experienced grade 4 haematological and /or grade 3 - 4 non-haematological toxicity . Published toxicity ( MAX2 ) , diastolic blood pressure , marrow invasion and lactate dehydrogenase ( LDH ) were all associated with toxicity ( P<0.1 ) ; Body Mass Index , previous chemotherapy , red blood cells , platelets , polymedication with dose-intensity ; and polymedication with FACT-G change . After adjustment for the published toxicity , the variables retained their significance , except for LDH and polymedication ( for dose-intensity ) . Although the size of this pilot study imposes a cautious interpretation , patient-related and chemotherapy-related variables correlated independently with toxicity . Design ing a composite predictive score to use in assessing the toxicity of multiple chemotherapy regimens therefore appears to be a valid undertaking PURPOSE This analysis of data from a r and omized trial of chemotherapy in epithelial ovarian cancer sought to determine whether a relationship exists between the presence and severity of the most commonly observed toxic effects and the corresponding quality of life ( QOL ) items . PATIENTS AND METHODS One hundred fifty-two eligible patients accrued from Canada by the National Cancer Institute of Canada Clinical Trials Group on a r and omized trial of paclitaxel and cisplatin versus cyclophosphamide/cisplatin  were included in the analysis . Toxicity to the chemotherapeutic treatments was subjectively evaluated using a trial-specific checklist for ovarian cancer and the European Organization for Research and Treatment of Cancer QLQ C30 + 3 question naire . Assessment s were conducted at baseline , before each cycle of treatment ( 3 weeks ) , and at each 3-month follow-up during the next 2 years ( or until progression ) . RESULTS The most frequently observed symptoms experienced during or shortly following chemotherapy were neurosensory loss , lethargy , nausea , vomiting , and alopecia . Regression analyses revealed that change scores of QOL items related to motor weakness and gastrointestinal pain were common predictors for the change global QOL score during protocol treatment ; and change scores of QOL items related to lethargy or fatigue and change toxicity grade of mood predicted the change global QOL score after patients were off treatment . CONCLUSION The use of the European Organization for Research and Treatment of Cancer QLQ C30 + 3 and trial-specific checklist was able to assess the effect of expected toxicities on patient ' s QOL during and following treatment , and so may be useful in addressing the concerns regarding method ological issues that have limited the acquisition of prospect i ve , longitudinal treatment-related toxicity data BACKGROUND Whether or not toxicity predicts clinical outcomes has long been a question regarding cancer treatments . While prior studies have focused on specific cancers , therapies , and toxicities , no comprehensive evidence exists on whether treatment toxicity predicts favorable outcomes . METHODS We abstract ed treatment toxicity and clinical outcome data from a sample of phase III oncology r and omized clinical trials ( n = 99 trials ) . We investigated whether treatments with relatively greater toxicity compared with their controls had relatively higher , lower , or equivocal rates of clinical efficacy , measured by progression-free survival ( PFS ) and overall survival ( OS ) . Several toxicities were assessed ( all grade s , grade s III/IV , cutaneous rash , gastrointestinal toxicity , and myelosuppression ) . RESULTS Toxicity and efficacy were greater among treatments than controls ( e.g. 3.5 instances of all- grade toxicity per patient in treatment arms versus 2.8 instances in controls , P < 0.001 ; mean PFS of 9.1 months across treatment arms versus 7.1 months across controls , P < 0.001 ; mean OS of 18.6 months across treatment arms versus 16.9 months across controls , P < 0.001 ) . Across trials , greater relative treatment toxicity was strongly associated with greater PFS in treatments versus controls ( P < 0.001 ) , but not OS ( P = 0.44 ) . Although higher relative rates of myelosuppression and cutaneous rash among treatments were not associated with greater treatment efficacy , greater relative gastrointestinal toxicity among treatments was associated with greater relative PFS compared with controls ( P = 0.007 ) . CONCLUSION Across trials , treatments with relatively greater all- grade toxicity compared with controls are associated with relatively greater PFS but not OS 109 Background : Toxicity related hospitalizations during chemotherapy are poorly reported in the literature . We sought to compare " real world " versus clinical trial rates of hospitalizations among patients with metastatic non-small cell lung cancer ( mNSCLC ) receiving chemotherapy .  We hypothesised that hospitalization rates in real life patients would be significantly higher . METHODS We conducted a systematic review of Medline and EMBASE ( 1946-June 2013 ) to identify articles reporting  hospitalization rates during chemotherapy in patients with cancer . Both observational studies and clinical trials were eligible . This report focuses on patients with mNSCLC receiving palliative chemotherapy  as data was available for this clinical scenario in both the observational and clinical trial setting , allowing comparison . Study results were abstract ed using a st and ardised form . Summary statistics were used to describe results and the chi-square test used to compare hospitalization rates . RESULTS The search identified 61 articles ( all published after 1987 ) , of which 16 were clinical trials and 45 were observational ( " real world " ) studies . Nine studies examined chemotherapy in mNSCLC - four observational studies and five r and omised trials . The four observational studies included 7,456 patients ; three included patients on any chemotherapy while the other focused on doublet regimens . Of the five r and omised trials which included 3,962 patients , three treated patients with platinum doublets and two used single-agent chemotherapy .  The real life cohort was older ( 70 years vs. 62 years ) . The aggregate hospitalization rate among real life patients was significantly higher than among trial patients ( 49 % vs. 16 % , OR=7.7 , 95 % CI 7 - 8.5 , p-value < 0.0001 ) . Performance status and type of chemotherapy were associated with hospitalization during chemotherapy in clinical trials while type of chemotherapy was a risk factor in observational studies . CONCLUSIONS Clinical trials in mNSCLC consistently report lower rates of hospitalization than real life cohorts of patients undergoing similar therapies but very few clinical trials report this information PURPOSE The North Central Cancer Treatment Group performed a phase III trial to determine whether chemotherapy plus either bid radiation therapy ( RT ) or daily ( qd ) RT result ed in a better outcome for patients with stage III non-small-cell lung cancer ( NSCLC ) . No difference in survival was identified between the two arms . This secondary analysis was performed to examine the relationship between patient age and outcome . PATIENTS AND METHODS Two hundred forty-six patients were r and omized to receive etoposide plus cisplatin and either RT qd or split-course RT bid . This retrospective study compared the outcomes of patients aged > /=70 years ( " elderly patients ") with those of younger individuals . Of the 244 assessable patients , 63 ( 26 % ) were elderly , and 181 ( 74 % ) were younger individuals . RESULTS The 2-year and 5-year survival rates were 39 % and 18 % , respectively , in patients younger than 70 years , compared with 36 % and 13 % , respectively , in elderly patients ( P = .4 ) . Grade 4 + toxicity occurred in 62 % of patients younger than 70 years compared with 81 % of elderly patients ( P = .007 ) . Grade 4 + hematologic toxicity occurred in 56 % of patients younger than 70 years , compared with 78 % of elderly patients ( P = .003 ) . Grade 4 + pneumonitis occurred in 1 % of those younger than 70 years , compared with 6 % of elderly patients ( P = .02 ) . CONCLUSION Toxicity , especially myelosuppression and pneumonitis , was more pronounced in the elderly patients receiving combined-modality therapy for locally advanced NSCLC . Despite increased toxicity , elderly patients have survival rates equivalent to younger individuals . Therefore , fit , elderly patients with locally advanced NSCLC should be encouraged to receive combined-modality therapy , preferably on clinical trials with cautious , judicious monitoring . Future studies should explore ways to decrease toxicity of therapy in elderly patients The purpose of this study was to vali date the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group — Neurotoxicity ( FACT/GOG-Ntx ) question naire . The FACT/GOG-Ntx is the FACT-G plus an eleven-item subscale ( Ntx subscale ) that evaluates symptoms and concerns associated specifically with chemotherapy-induced neuropathy . Two groups of women with ovarian cancer completed the FACT/GOG-Ntx : one group with known neurotoxicities and one group of chemotherapy-naive women newly diagnosed with ovarian cancer .  Levels of patient neuropathy , severity of toxicity , and patient quality of life from diagnosis of ovarian cancer to 12 months post-diagnosis were assessed . The Ntx subscale significantly differentiated the two groups at baseline and 3- and 6-month follow-ups , demonstrating significantly fewer problems among chemotherapy-naive patients than among patients with known neuropathy . The FACT/GOG-Ntx is a reliable and valid instrument for assessing the impact of neuropathy on health-related quality of life . The Ntx subscale demonstrated sensitivity to meaningful clinical distinctions and change over time PURPOSE / OBJECTIVES To determine whether improved monitoring through close follow-up with a nurse practitioner ( NP ) could enhance treatment compliance and decrease frequency of hospitalizations . DESIGN Retrospective chart review . SETTING An academic National Cancer Institute- design ated comprehensive cancer center . SAMPLE 151 patients aged 45 - 65 years diagnosed with stage III or IV oropharyngeal cancer . METHODS Patients were nonr and omized to one of two groups : a prechemotherapy clinic group and a weekly NP-led clinic group .  After examination of descriptive statistics , multiple linear and logistic regressions were used to compare groups across patient outcomes . MAIN RESEARCH VARIABLES Hospitalization , chemotherapy dose deviations , and chemotherapy treatment completion . FINDINGS The average number of visits during traditional treatment was three and , after initiation of the NP-led clinic , the number was six . The hospitalization rate was 28 % in the traditional clinic group compared to 12 % in the NP-led group . The rate of chemotherapy dose deviations was 48 % in the traditional clinic group compared to 6 % in the NP-led clinic group . Forty-six percent of patients in the traditional clinic group received the full seven scheduled doses of chemotherapy compared to 90 % of patients seen in the NP-led clinic group . CONCLUSIONS A weekly NP-led symptom management clinic reduces rates of hospitalization and chemotherapy dose deviations and increases chemotherapy completion in patients receiving intensive chemoradiotherapy for oropharyngeal cancer . IMPLICATION S FOR NURSING Patients receiving chemoradiotherapy benefit from close monitoring for toxicities by NPs to successfully complete their treatment and avoid hospitalization . KNOWLEDGE TRANSLATION Early interventions to manage toxicities in patients with head and neck cancer can improve outcomes . NPs are in a key position to manage these toxicities and , when symptoms are controlled , costs are reduced PURPOSE Inoperable locoregional recurrences of head- and -neck cancer in a previously irradiated volume represent a therapeutic dilemma . Chemotherapy alone has no curative potential , whereas reirradiation and concurrent chemoradiation can salvage a small fraction of patients . Mucosal toxicity of concurrent chemoradiation requires substantial dose reduction of chemotherapy . Alternating chemoradiation offers the chance to give both full-dose chemotherapy and radiotherapy . The latter may provide a particular advantage for recurrent , potentially radiation resistant tumors . The feasibility and efficacy of a full-dose docetaxel containing alternating chemoradiation schedule was tested . PATIENTS AND METHODS Twenty-seven patients ( Karnofsky performance status score > /=70 % ) with histologically proven recurrent squamous cell cancer that occurred > /= 6 months in a previously irradiated area ( > /= 60 Gy ) were considered unresectable and unsuitable for brachytherapy .  Alternating chemoradiation consisted of 3 cycles of docetaxel 60 mg/m(2 ) d1 and cisplatin 15 mg/m(2 ) d2 - 5 , q d22 , and involved field radiotherapy 2.0 Gy every day d8 - 12 , d15 - 19 , d29 - 33 , and d36 - 40 ( 40.0 Gy total dose ) . Dose reduction of docetaxel to 50 mg/m(2 ) was necessary , because of hematologic toxicity in the first 12 patients . RESULTS Alternating chemoreirradiation was applied as planned in 12 of 27 patients , with reirradiation completed per protocol in 81 % . Overall , patients received 83 % of the intended dose of docetaxel and 73 % of cisplatin .  Third-degree common toxicity criteria mucositis occurred in 15 % , leukopenia of > /= third degree by common toxicity criteria in 37 % , and 3 early deaths were observed . Median time to follow-up , time to local progression , median survival , and 3-year survival rates were 42 months , 10 months , 10 months , and 18 % , respectively . CONCLUSIONS Alternating chemoreirradiation in recurrences of head- and -neck cancer result ed in 80 % overall response with acceptable toxicity . A significant minority of patients had durable tumor control with a chance of long-term survival PURPOSE The safety of combined immunotherapy and thoracic radiation therapy ( iRT )  has been understudied . We evaluated toxicities in patients receiving iRT from 3 single-institutional phase 1/2 trials . METHODS AND MATERIAL S Clinical /treatment characteristics and toxicities ( per the Common Toxicity Criteria for Adverse Events , version 4.0 ) were extracted . For purpose s of this analysis , groupings were made into ( 1 ) patients receiving immunotherapy plus stereotactic body radiation therapy ( 50 Gy/4 fractions or 60 Gy/10 fractions ) , ( 2 ) immunotherapy plus 45 Gy/15 fractions , and ( 3 ) twice-daily chemoimmunoradiotherapy ( 45 Gy in twice-daily fractions ) . RESULTS None of the 60 patients undergoing immunotherapy plus stereotactic body radiation therapy ( 50 Gy , n = 49 ; 60 Gy , n = 11 ) experienced grade ≥4 events . There were 34 instances of any grade 3 event ( in 15 total patients ) , with 9 pulmonary specific grade 3 events ( in 4 patients ) . In the patients receiving 45 Gy/15 fractions ( small cell lung cancers , n = 26 ; non-small cell lung cancers , n = 27 ) , there were 2 grade 4 events ( in the same patient ) , along with 17 grade 3 toxicities experienced by 10 total patients ( 2 pulmonary specific ) . Lastly , in the twice-daily cohort ( n = 22 ) , there were 5 grade 4 events ( 3 of which occurred in 1 patient ) and 16 grade 3 toxicities occurring in 8 total patients ( half of which were hematologic ) . CONCLUSIONS Administration of combined iRT is safe in the short term . Toxicities did not appreciably associate with demographics or dosimetry We present new statistical analyses of data arising from a clinical trial design ed to compare two-stage dynamic treatment regimes ( DTRs ) for advanced prostate cancer . The trial protocol m and ated that patients be initially r and omized among four chemotherapies , and that those who responded poorly be re-r and omized to one of the remaining c and i date therapies .  The primary aim was to compare the DTRs ’ overall success rates , with success defined by the occurrence of successful responses in each of two consecutive courses of the patient ’s therapy . Of the 150 study participants , 47 did not complete their therapy as per the algorithm . However , 35 of them did so for reasons that precluded further chemotherapy , that is , toxicity and /or progressive disease . Consequently , rather than comparing the overall success rates of the DTRs in the unrealistic event that these patients had remained on their assigned chemotherapies , we conducted an analysis that compared viable switch rules defined by the per- protocol rules but with the additional provision that patients who developed toxicity or progressive disease switch to a non-prespecified therapeutic or palliative strategy . This modification involved consideration of bivariate per-course outcomes encoding both efficacy and toxicity . We used numerical scores elicited from the trial ’s principal investigator to quantify the clinical desirability of each bivariate per-course outcome , and defined one endpoint as their average over all courses of treatment . Two other simpler sets of scores as well as log survival time were also used as endpoints . Estimation of each DTR-specific mean score was conducted using inverse probability weighted methods that assumed that missingness in the 12 remaining dropouts was informative but explainable in that it only depended on past recorded data . We conducted additional worst- and best-case analyses to evaluate sensitivity of our findings to extreme departures from the explainable dropout assumption PURPOSE Validation of a prospect i ve , risk-adapted strategy for early-stage non-small-cell lung cancer ( NSCLC ) patients treated with stereotactic body radiotherapy ( SBRT ) .  METHODS AND MATERIAL S Patients with a T1 - 3N0M0 ( American Joint Committee on Cancer 6th edition ) NSCLC were accrued . Using the Radiation Therapy Oncology Group definition , patients were treated to a total dose of 60,Gy in three fractions for peripherally located lesions and four fractions for central ly located lesions . The primary endpoint was toxicity , grade d according to the Radiation Therapy Oncology Group acute and late morbidity scoring system , and the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 . Secondary endpoints were local control and survival . RESULTS A total of 40 patients were included , 17 with a central ly located lesion . The lung toxicity-free survival estimate at 2 years was 74 % and was related to the location ( central vs. peripheral ) and the size of the target volume . No dose volumetric parameters could predict the occurrence of lung toxicity . One patient died because of treatment-related toxicity . The 1-year and 2-year local progression-free survival estimates were 97 % and 84 % , respectively , and were related to stage ( T1 vs. T2 ) related ( p = 0.006 ) . Local failure was not more frequent for patients treated in four fractions . The 1-year local progression-free survival estimate dropped below 80 % for lesions with a diameter of more than 4 cm . CONCLUSION The proposed risk-adapted strategy for both central ly and peripherally located lesions showed an acceptable toxicity profile while maintaining excellent local control rates . The correlation between local control and tumor diameter calls for the inclusion of tumor stage as a variable in future study design PURPOSE Radiation therapy ( RT ) causes acute and late toxicities that affect various organs and functions . In a large cohort of patients treated with RT for localized head and neck cancer ( HNC ) , we prospect ively assessed the occurrence of RT-induced acute and late toxicities and identified characteristics that predicted these toxicities . METHODS AND MATERIAL S We conducted a r and omized trial among 540 patients treated with RT for localized HNC to assess whether vitamin E supplementation could improve disease outcomes . Adverse effects of RT were assessed using the  Radiation Therapy Oncology Group Acute Radiation Morbidity Criteria during RT and one month after RT , and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme at six and 12 months after RT . The most severe adverse effect among the organs/tissues was selected as an overall measure of either acute or late toxicity . Grade 3 and 4 toxicities were considered as severe . Stepwise multivariate logistic regression models were used to identify all independent predictors ( p < 0.05 ) of acute or late toxicity and to estimate odds ratios ( OR ) for severe toxicity with their 95 % confidence intervals ( CI ) . RESULTS Grade 3 or 4 toxicity was observed in 23 % and 4 % of patients , respectively , for acute and late toxicity . Four independent predictors of severe acute toxicity were identified : sex ( female vs. male : OR = 1.72 , 95 % confidence interval [ CI ] : 1.06 - 2.80 ) , Karnofsky Performance Status ( OR = 0.67 for a 10-point increment , 95 % CI : 0.52 - 0.88 ) , body mass index ( above 25 vs. below : OR = 1.88 , 95 % CI : 1.22 - 2.90 ) , TNM stage ( Stage II vs. I : OR = 1.91 , 95 % CI : 1.25 - 2.92 ) . Two independent predictors were found for severe late toxicity : female sex ( OR = 3.96 , 95 % CI : 1.41 - 11.08 ) and weight loss during RT ( OR = 1.26 for a 1 kg increment , 95 % CI : 1.12 - 1.41 ) . CONCLUSIONS Knowledge of these predictors easily collected in a clinical setting could help tailoring therapies to reduce toxicities among patients treated with RT for HNC PURPOSE Long-term and rogen suppression plus radiotherapy ( AS+RT ) is st and ard treatment of high-risk prostate cancer . A r and omized trial , Radiation Therapy Oncology Group trial 9902 , was undertaken to determine whether adjuvant chemotherapy with paclitaxel , estramustine , and etoposide ( TEE ) plus AS+RT would improve disease outcomes with acceptable toxicity . METHODS AND MATERIAL S High-risk ( prostate-specific antigen 20 - 100 ng/mL and Gleason score > or=7 ; or Stage T2 or greater , Gleason score 8 , prostate-specific antigen level < 100 ng/mL ) nonmetastatic prostate cancer patients were r and omized to AS+RT ( Arm 1 ) vs. AS+RT plus four cycles of TEE ( Arm 2 ) . TEE was delivered 4 weeks after RT . AS continued for 2 years for both treatment arms . RT began after 8 weeks of AS began . RESULTS The Radiation Therapy Oncology Group 9902 trial opened January 11 , 2000 . Excess thromboembolic toxicity was noted , leading to study closure October 4 , 2004 . A total of 397 patients were accrued , and the data for 381 were analyzable . An acute and long-term toxicity analysis was performed . The worst overall toxicities during treatment were increased for Arm 2 . Of the 192 patients , 136 ( 71 % ) on Arm 2 had RTOG Grade 3 or greater toxicity compared with 70 ( 37 % ) of 189 patients on Arm 1 . Statistically significant increases in hematologic toxicity ( p < 0.0001 ) and gastrointestinal toxicity ( p = 0.017 ) but not genitourinary toxicity ( p = 0.07 ) were noted during treatment . Two Grade 5 complications related to neutropenic infection occurred in Arm 2 . Three cases of myelodysplasia/acute myelogenous leukemia were noted in Arm 2 . At 2 and 3 years after therapy completion , excess long-term toxicity was not observed in Arm 2 . CONCLUSION TEE was associated with significantly increased toxicity during treatment . The toxicity profiles did not differ at 2 and 3 years after therapy . Toxicity is an important consideration in the design of trials using adjuvant chemotherapy for prostate cancer
This review shows that a significant proportion of patients in curative-intent clinical trials experience toxicities that result in dose modifications-dose reduction , dose delays or missed doses-despite strict selection criteria and intense monitoring .
Toxicities of systemic cancer therapies are often less frequently observed in clinical trials than in clinical practice , due to the careful selection of patients with fewer comorbidities .
Although guidelines exist for the estimation of chemotherapy dose , clinical factors like age , comorbid illness and extremes of body habitus are not considered in the method of dose calculation , which can result in significant toxicity .