Patient-reported acute fatigue in elderly breast cancer patients treated with and without regional nodal radiation.

PURPOSE: Although regional nodal irradiation (RNI) improves outcomes in breast cancer (BC) patients, it is associated with increased toxicity. Therefore, controversy still exists surrounding its indications. The purpose of this study was to evaluate and compare patient-reported acute fatigue in elderly BC patients with and without regional nodal radiation (RNI). METHODS: Elderly breast cancer patients (≥ 65 years) treated with adjuvant radiotherapy (RT) between 2012 and 2017 were identified from a prospective database. The validated Edmonton Symptom Assessment System-revised (ESAS-r) questionnaire, which assesses fatigue, was completed prior to (baseline), during, at end of RT and first follow-up (3-6 months). Symptoms were rated on a 10-point Likert scale, with higher scores indicating higher fatigue. Patient's treatment characteristics were also recorded prospectively. This was a retrospective study which identified elderly breast cancer patients who had received adjuvant radiation, completed ESAS-r prospectively and provided research consent for using ESAS-r. Patients were divided into two cohorts: those who received RNI (cohort 1) and those who did not (cohort 2). A minimal clinically important difference (MID) was defined using an anchor of ≥ 1-point compared to baseline. The proportion of patients reporting a change in fatigue at the end of RT was evaluated. To test the robustness of the results, dynamic changes of fatigue scores over time were further compared between the cohorts using a general linear mixed model (GLMM) after assuming individual patient with random effect. Univariate and multivariable logistic regression were conducted to assess the association between RNI and MID after adjusting for potential confounders. In addition to longitudinal analysis, a multivariable mixed effect model was developed to determine the association of RNI with fatigue after adjusting for potential confounders. A two-tailed p value ≤ 0.05 was considered statistically significant. RESULTS: Of the 1198 patients, 859 had provided research consent and completed the ESAS-r at baseline and any other time-point and were included in the longitudinal analysis (cohort 1 = 159, cohort 2 = 700), while 637 (cohort 1 = 135, cohort 2 = 502) patients completed the ESAS-r at baseline and end of radiotherapy and were included in the anchor-based analysis. Mean age at diagnosis was similar between the groups: cohort 1; 71.5 ± 5.7 vs. cohort; 2 72 ± 5.4 years (total 71.8 ± 5.5). Overall, cohort 1 had higher stage (Stage 3: 32.7% vs 3.6%, p < 0.001) and reception of chemotherapy (68.6% vs. 16.1%, p < 0.001). Mean baseline fatigue was higher for cohort 1 vs. 2 (2.7 ± 2.5 vs. 2.1 ± 2.3, p = 0.006). On univariate and multivariable analyses, RNI was not associated with an increased odd of MID for fatigue at the end of RT (44% vs. 47%; OR 0.89, 95% CI 0.61-1.30, p = 0.56). After adjusting for confounders (age, duration of RT, endocrine therapy), treatment with RNI was not associated with increased odds of worse fatigue at the end of RT (OR 1.33, 95% CI 0.85-2.10, p = 0.22). Higher baseline fatigue (OR 0.86, 95% CI 0.79-0.92, p < 0.001) and receipt of chemotherapy had decreased odds (OR 0.50, 95% CI 0.32-0.86, p = 0.001) and were the only factors associated with decreased odds of MID. Dynamic changes showed a significant worsening of fatigue scores over time (p < 0.001) towards the end of RT and recovery at first follow-up (p < 0.001) with no difference between the cohorts (p = 0.38); both experienced parallel worsening of fatigue levels over time (cohort*time p = 0.71 and cohort*time2p = 0.78). On multivariable analysis earlier stage, the absence of chemotherapy and higher baseline depression were independent predictors of worse fatigue scores over time (p = 0.01, p = 0.003, and p = 0.02, respectively). CONCLUSION: The addition of RNI in elderly BC patients is not associated with a significant worsening of patient-reported fatigue. Predictors of acute fatigue will enable shared decision making between patients and clinicians.

Clinical impact of mutation fraction in epidermal growth factor receptor mutation positive NSCLC patients.

BACKGROUND: We examined clinical outcomes in a population-based cohort of EGFR mutant advanced NSCLC patients, exploring the potential role of factors including tumour EGFR mutation fraction and cellularity in predicting outcomes. METHODS: A cohort of patients with EGFR mutant advanced NSCLC was identified (N =2 93); clinical outcomes, pathologic and treatment details were collected. Tumour response was determined from radiology and clinical notes. Association between demographic and pathologic variables EGFR TKI response, time to treatment failure (TTF) and overall survival (OS) was examined using logistic regression and proportional hazards regression. EGFR TKI response rates were summarised by percent mutation fraction to explore their association. RESULTS: Higher mutation fraction was associated with greater EGFR TKI response rate (odds ratio 1.58, 95% CI = 1.21-2.07, P = 0.0008), longer TTF (hazard ratio 0.80, 95% CI = 0.68-0.92, P = 0.003) and better OS (hazard ratio 0.81, 95% CI = 0.67-0.99, P = 0.04). However, even in patients with ⩽ 5% mutation fraction, response rate was 34%. Females had longer TTF (P = 0.02). CONCLUSIONS: EGFR mutation fraction in tumour samples was significantly associated with response, TTF and OS. Despite this, no lower level of mutation fraction was detected for which EGFR TKI should be withheld in those with activating EGFR mutations.

Real-world chemotherapy treatment patterns in metastatic non-small cell lung cancer: Are patients undertreated?

BACKGROUND: New therapies for metastatic non-small cell lung cancer (NSCLC) have improved survival in clinical trials. However, only a minority of patients receive systemic therapy. This article reports treatment patterns and outcomes for a population of Canadian patients with metastatic NSCLC (Ontario). METHODS: Patients diagnosed with stage IV NSCLC from 2005 to 2009 were identified through multiple linked provincial databases. Patient demographics, systemic treatment, and survival were examined over time. RESULTS: Metastatic NSCLC patients (n = 8113) were identified. The median age was 68 years; 39% had adenocarcinoma, 14% had squamous carcinoma, and a higher than expected proportion (43%) had NSCLC not otherwise specified. Only 24% the patients received first-line chemotherapy; only 31% of these received second-line chemotherapy. More patients received systemic therapy over time (from 19% in 2005 to 26% in 2009, P < .0001). Patients who were less than 70 years old or had adenocarcinoma were more likely to receive systemic therapy (P < .0001 for both). The median survival, regardless of age, for those selected to receive first-line cisplatin-gemcitabine chemotherapy was longer than that for those receiving other nonpemetrexed platinum doublets at 11.6 months (P = .0002). Patients with nonsquamous histology who were treated with second-line pemetrexed had longer median survival than those treated with docetaxel (19.8 vs 14.1 months, P < .0001). CONCLUSIONS: Most patients with metastatic NSCLC in the general population still do not receive systemic therapy. Those selected for first- and second-line systemic treatment, including older patients, have survival outcomes comparable to clinical trial results. Older patients and patients with squamous histology are less likely to receive chemotherapy. The low levels of treatment utilization in this study warrant further investigation.

A phase-1 trial of linsitinib (OSI-906) in combination with bortezomib and dexamethasone for the treatment of relapsed/refractory multiple myeloma.

We report results of a phase-1 study evaluating the safety and anti-cancer activity of the small molecule insulin-like growth factor-1 receptor (IGF-1R) inhibitor, linsitinib combined with bortezomib, and dexamethasone in relapsed/refractory multiple myeloma. Nineteen patients were enrolled across four dose-escalation cohorts (75-150 mg bid). The maximum tolerated dose of linsitinib was 125 mg. The most frequent Grade 3/4 AEs occurring in ≥10% of patients were thrombocytopenia (53%), bone pain (26%), neutropenia (21%), diarrhea (14%), anemia (14%), rash (10%), and lung infection (10%). Study discontinuation due to treatment-related AEs was low (16%). Across all cohorts the ORR was 61% (95% CI: 28.9-75.6%). Three partial response or greater and one stable disease were observed in proteasome inhibitor (PI) refractory patients (n = 5). Median PFS was 7.1 months (95% CI: 3.6-NA). Linsitinib plus bortezomib and dexamethasone demonstrate a manageable safety profile while the clinical benefit particularly in PI refractory patients warrants further exploration.

An open-label, pharmacokinetic study of lenalidomide and dexamethasone therapy in previously untreated multiple myeloma (MM) patients with various degrees of renal impairment - validation of official dosing guidelines.

Lenalidomide is a backbone agent in the treatment of multiple myeloma, but dose adjustment is required for those with renal impairment (RI). We evaluated the pharmacokinetics (PK) and safety of lenalidomide and dexamethasone as frontline pre-transplant induction, with doses adjusted at start of each cycle based on creatinine clearance, as per the official dosing guidelines. After 4 cycles, PK studies showed that patients with moderate RI (30 ≤ CrCl < 60 mL/min) receiving 10 mg dosing may be under-dosed and those with severe RI (CrCl <30ml/min) appeared appropriately dosed initially, but sustained significant decreases in maximum serum concentration (Cmax) after repeated dosing, due to rapid clinical improvement and enhanced drug clearance. PK drug monitoring during cycle 1 may facilitate appropriate and timely dose adjustments. Adverse events rates did not vary based on severity of RI. No patient discontinued lenalidomide for toxicity. This supports the feasibility and safety of frontline lenalidomide in transplant-eligible patients with RI.

A phase 2 study of ofatumumab (Arzerra®) in combination with a pan-AKT inhibitor (afuresertib) in previously treated patients with chronic lymphocytic leukemia (CLL).

AKT plays a centralized role in tumor proliferation and survival and is aberrantly activated in chronic lymphocytic leukemia (CLL). In this phase 2 trial, 30 relapsed/refractory CLL patients were treated with combination afuresertib, a novel oral AKT inhibitor, and ofatumumab for 6 months, followed by afuresertib maintenance for 12 months. We aimed to achieve deeper and more durable responses, without requiring long-term continuous treatment. Treatment was generally well tolerated but respiratory infections were common, with 18% severe requiring hospitalization. Hematologic toxicities were manageable (grade 3-4 neutropenia 39%). At a median follow-up of 13.4 months, overall responses were 50% (complete responses 3.6%). Median progression-free survival was 8.5 months and overall survival 34.8 months. Combination therapy with ofatumumab and afuresertib is active and well tolerated, but does not appear to lead to durable responses and may not provide additional benefit over single-agent ofatumumab in relapsed/refractory CLL. Novel agent combinations are currently undergoing intense investigation.

A phase 2 study of lenalidomide and dexamethasone in previously untreated patients with chronic lymphocytic leukemia (CLL).

Lenalidomide has anti-tumor activity in CLL but can be complicated by tumor lysis syndrome (TLS) and tumor flare (TF). In our previous study using low-dose lenalidomide in treatment-naive CLL, TLS was averted but TF remained frequent and complete responses (CR) were rare, despite treatment to progression. The addition of dexamethasone may mitigate TF and enable lenalidomide dose escalation, achieving durable response without long-term use. In this phase 2 trial, 31 treatment-naive CLL patients received lenalidomide (target 25mg daily) plus dexamethasone for a finite 18 cycles. No patients developed TLS and TF was infrequent. Overall responses were 74.2% (CR 9.7%) and median progression-free survival 27 months. Cereblon-binding proteins IKZF1 and IKZF3 were largely downregulated, with associated increased IRF4 levels. We therefore report that lenalidomide plus dexamethasone can achieve durable responses in a subset of patients without continuing therapy until progression. Upregulation of IRF4 may contribute to anti-CLL activity of immunomodulatory agents. This trial was registered at www.clinicaltrials.gov as NCT01133743.

Ultracentral Tumors Treated With Stereotactic Body Radiotherapy: Single-Institution Experience.

INTRODUCTION: Patients with ultracentral lung tumors, whose planning target volume directly contacts or overlaps the proximal bronchial tree, trachea, esophagus, pulmonary vein, or pulmonary artery, may be at higher risk of toxicity when treated with stereotactic body radiotherapy (SBRT). We reviewed the outcomes and toxicities of ultracentral lung tumors and compared the results with central lung tumors. PATIENTS AND METHODS: A review of our institutional prospective database of patients treated with lung SBRT from January 2006 to December 2015 was conducted. Patients with central tumors (RTOG 0813 definition) and ultracentral tumors were included. RESULTS: In total, 180 central and 26 ultracentral tumors were analyzed. The majority of patients received 60 Gy in 8 fractions (53.9%) or 48 Gy in 4 fractions (29.1%). The rates of any grade 2 or higher toxicity were 8.4% (n = 16) in the central group and 7.9% (n = 2) in the ultracentral group (P = .88). There were no observed grade 4 or 5 toxicities. In the nonmetastatic primary lung cancer cohort (n = 182), the median overall survival was 39.4 months versus 23.8 months (P = .40) and cause-specific survival was 55.5 months versus 28.2 months (P = .34) for central and ultracentral tumors, respectively. The 2-year cumulative local, regional, and distant failure rates were 3.3% versus 0 (P = .36), 9.1% versus 5.0% (P = .5), and 17.7% versus 18.7% (P = .63) in the central and ultracentral groups, respectively. CONCLUSION: In our experience, with strict adherence to planning parameters, SBRT to ultracentral tumors resulted in effective local control and no excessive risk of toxicity compared to central tumors.

Low Incidence of Esophageal Toxicity After Lung Stereotactic Body Radiation Therapy: Are Current Esophageal Dose Constraints Too Conservative?

PURPOSE: To explore and quantify the relationship between esophageal dose and toxicity in the setting of lung stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: This analysis was conducted on the basis of a prospective study of patients treated with SBRT at our institution from October 2004 to December 2015. Most patients were treated with 54 Gy/3 fractions, 48 Gy/4 fractions alternate days, or 60 Gy/8 fractions daily. Toxicity was prospectively graded using Common Terminology Criteria for Adverse Events version 3.0. Logistic regression was used to estimate the risk of esophageal toxicity as a function of radiation therapy dose, in 2-Gy-equivalent dose, using an α/ß ratio of 3 Gy in the linear-quadratic model. RESULTS: A total of 632 patients were analyzed. The median follow-up was 20.8 months. Median overall survival was 35.3 months. The rate of late or acute grade ≥1 esophageal toxicity, including dysphagia, odynophagia, and esophagitis, was 3.3% (n = 21). The median (range) esophageal doses were 11.8 Gy (0.2-48.2 Gy), 10.34 Gy (0.17-44.5 Gy), and 9.63 Gy (0.08-43 Gy) for Dmax, D1cc, and D2cc, respectively. A 15% risk of esophageal toxicity was associated with a 2-Gy-equivalent dose of Dmax 141.6 Gy, D1cc 123.61 Gy, and D2cc 117.6 Gy. Of the 21 patients who experienced esophageal toxicity, only 1 patient had grade 3 toxicity, and the remainder had grade 2 or lower toxicity. CONCLUSIONS: The observed rate of toxicity was low, despite some patients receiving relatively high doses to the esophagus. A prospective study in a targeted population, for example patients with ultracentral tumors, may provide more accurate dose-toxicity parameters.

Distribution and Impact of Comorbidities on Survival and Leukemic Transformation in Myeloproliferative Neoplasm-Associated Myelofibrosis: A Retrospective Cohort Study.

BACKGROUND: We sought to describe the distribution and impact of comorbidities on outcomes in patients with myelofibrosis, a disease characterized by aberrant bone marrow function with eventual fibrosis. Comorbidities were scored using the Adult Comorbidity Evaluation-27 (ACE-27) and the Hematopoietic Cell Transplant Comorbidity Index (HCT-CI), in which a score ≥ 3 indicates severe comorbidities. PATIENTS AND METHODS: We conducted a retrospective study of 306 patients with a confirmed diagnosis of myelofibrosis. Patients were seen from 1999 to 2014 with a median follow-up of 2 years. Multivariable Cox proportional hazards models were constructed to assess the impact of comorbidities on overall survival and leukemic transformation from the date of presentation to our center. A series of descriptive analyses were performed examining the distribution of comorbidities captured by the scales. RESULTS: On multivariable survival analysis, an ACE-27 score of 3 was associated with an almost twofold increase in the risk of all-cause death (hazard ratio [HR] 1.95; 95% confidence interval [CI], 1.06-3.58; P = .03) compared with a lower score of 0 to 1. An HCT-CI score ≥ 3 was marginally significantly associated with an increased risk of all-cause death (HR 1.60; 95% CI 0.96-2.68; P = .07). ACE-27 captured a greater spectrum of cardiovascular and venous thrombotic disease. No impact of comorbidities on leukemic transformation was observed. CONCLUSIONS: Although the presence of severe comorbidities was lower when assessed by ACE-27 (13%) compared with HCT-CI (23%), and the spectrums of comorbidities captured were different, the overall impact of severe comorbidities as assessed by both scales appears to be similar and associated with a survival disadvantage.

Effect of Red Blood Cell Transfusion Dependence on the Natural History of Myeloproliferative Neoplasm-Associated Myelofibrosis.

BACKGROUND: There are 2 widely used criteria for red blood cell (RBC) transfusion dependence in persons with myeloproliferative neoplasm (MPN)-associated myelofibrosis: (1) the International Working Group-Myelofibrosis Research and Therapy (IWG-MRT) criteria (receipt of 2 U RBC in the preceding month); and (2) the Rand-Delphi definition (2 U RBC per month averaged over 3 months). We studied effect of these criteria on survival and risk of leukemic transformation in 259 subjects with MPN-associated myelofibrosis. PATIENTS AND METHODS: On the basis of hemoglobin (Hb) and transfusion history, subjects were assigned to 1 of the 4 cohorts: (1) Hb ≥ 100 g/L (n = 136; 52%) and no RBC transfusions in the preceding 4 months; (2) Hb < 100 g/L, and no RBC transfusions in the preceding 4 months (n = 56; 22%); (3) subjects who met IWG-MRT criteria, but not the Rand-Delphi criteria for RBC transfusion dependence (n = 34; 13%); and (4) subjects who met the Rand-Delphi criteria for RBC transfusion dependence (n = 33; 13%). RESULTS: Three-year probability of survival among the 4 cohorts was 81% (95% confidence interval [CI], 71-87), 55% (95% CI, 36-71), 52% (95% CI, 31-69), and 47% (95% CI, 24-67), respectively (P = .0005). There was no significant difference in baseline characteristics or survival between cohorts 3 and 4 and they were combined for subsequent analyses. In multivariate analyses, subjects who met either definition of RBC transfusion dependence had significantly worse survival (hazard ratio, 2.61; 95% CI, 1.38-4.96; P = .01). CONCLUSION: RBC transfusion dependence is associated with worse survival irrespective of definition of transfusion dependence. No effect of anemia or RBC transfusion dependence on leukemic transformation was observed.

Prospective comparison of breast pain in patients participating in a randomized trial of breast-conserving surgery and tamoxifen with or without radiotherapy.

PURPOSE: To determine whether breast pain affects quality of life (QOL) after breast-conserving surgery and tamoxifen (TAM) with or without adjuvant breast radiotherapy (RT). METHODS AND MATERIALS: A randomized clinical trial was carried out at the Princess Margaret Hospital between 1992 and 2000 to evaluate the need for breast RT in addition to TAM in women >or=50 years treated with breast-conserving surgery for T1-T2N0 breast cancer. A companion study to assess breast pain was carried out during the last 2 years of the randomized clinical trial. The short-form McGill Pain Questionnaire (SF-MPQ), the European Organization for Research and Treatment of Cancer (EORTC) QOL (QLQ-C30) and EORTC breast cancer module (QLQ-BR23) questionnaires were completed by patients within 1 week of randomization in the randomized clinical trial (baseline) and at 3, 6, and 12 months. RESULTS: Eighty-six patients participated in the breast pain study; 41 received RT plus TAM and 45 received TAM alone. The median age was 70 years (range 51-80). The baseline pain and QOL scores were similar for the two groups. No significant difference was found between the two groups for each scale of the QLQ-C30 and QLQ-BR23 questionnaires at 3, 6, or 12 months (p >0.100), except that at 12 months, the score for role function (QLQ-C30) was higher in the RT plus TAM group than in the RT-only group (p = 0.02). At 3 months, the difference between the mean scores for the SF-MPQ was 0.553 (p = 0.47). At 12 months, the pain scores had decreased in both groups; the difference was 0.199 (p = 0.71). The number of breast operations or surgical complications did not correlate with breast pain in either group. Acute RT toxicity scores did not correlate with breast pain or QOL scores at 12 months. CONCLUSION: These results suggest that breast RT does not significantly contribute to breast pain or adversely impact the QOL up to 12 months after treatment in postmenopausal patients with node-negative breast cancer who take TAM.

Treatment of muscle-invasive bladder cancer in Canada: A survey of genitourinary medical oncologists and urologists.

INTRODUCTION: Uptake of neoadjuvant chemotherapy (NC) for muscle invasive bladder cancer (MIBC) has been low despite evidence of a survival benefit. The primary aim of this study was to better understand why the rates are low and determine what factors specifically influence the decision to recommend NC for MIBC. METHODS: A 31-question survey was emailed between 2009 and 2011 to medical oncologists belonging to the Canadian Association of Genitourinary Medical Oncologists (CAGMO); and to urologists belonging to the Canadian Urologic Oncology Group (CUOG). We gathered data on practice characteristics, referrals for NC, factors influencing NC use, and chemotherapy regimens offered. Responses were summarized using descriptive statistics. RESULTS: In total, 26/30 (87%) medical oncologists and 25/84 (30%) urologists, who were primarily academic, completed the survey. Most clinicians (medical oncologists 96%, urologists 88%) recommended NC for MIBC, because they considered it to be the standard of care, but most medical oncologists saw ≤6 referrals annually. Performance status, presence of comorbidities and renal function were key considerations in offering NC. NC was not offered if performance status ≥2 (medical oncologists 38%, urologists 44%), age >80 (medical oncologists 46%, urologists 39%), or glomerular filtration rate ≤40 mL/min (medical oncologists 81%, urologists 50%). CONCLUSIONS: Most academic clinicians in Canada believe that cisplatin-based combination NC is the standard of care for MIBC and recommend it for patients with adequate performance status and renal function. Using a multidisciplinary approach to treat this disease may be one strategy to increase referral rates for NC and uptake of NC.

Single-agent lenalidomide in the treatment of previously untreated chronic lymphocytic leukemia.

PURPOSE: Lenalidomide is an oral immunomodulatory drug with multiple effects on the immune system and tumor cell microenvironment leading to inhibition of malignant cell growth. Based on encouraging reports of lenalidomide in relapsed and refractory chronic lymphocytic leukemia (CLL), we investigated the first-line use of single-agent lenalidomide in CLL. PATIENTS AND METHODS: Using a starting dose of lenalidomide 10 mg/d for 21 days of a 28-day cycle and weekly 5-mg dose escalations to a target of 25 mg, we encountered severe toxicities (tumor lysis, fatal sepsis) in the first two patients enrolled. The study was halted and the protocol amended to a more conservative regimen: starting dose of lenalidomide 2.5 mg with monthly escalations to a target dose of 10 mg, and extended tumor lysis prophylaxis and monitoring. Gene expression profiles from patient samples before and after 7 days of lenalidomide were performed. RESULTS: Twenty-five patients were enrolled on the amended protocol. No further tumor lysis events were reported. Tumor flare was common (88%) but mild. Grade 3 to 4 neutropenia occurred in 72% of patients, with only five episodes of febrile neutropenia. The overall response rate was 56% (no complete responses). Although rapid peripheral lymphocyte reductions were observed, rebound lymphocytoses during the week off-therapy were common. Lenalidomide-induced molecular changes enriched for cytoskeletal and immune-related genes were identified. CONCLUSION: Lenalidomide is clinically active as first-line CLL therapy and is well-tolerated if a conservative approach with slow dose escalation is used. A lenalidomide-induced molecular signature provides insights into its immunomodulatory mechanisms of action in CLL.

Concurrent cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy and radiotherapy for breast carcinoma: a well tolerated adjuvant regimen.

BACKGROUND: The current study was conducted to assess the toxicity of concurrent adjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy and radiotherapy (RT) for early breast carcinoma. METHODS: In the current study, the authors reviewed the records of 680 consecutive breast carcinoma patients who received adjuvant CMF at the Princess Margaret Hospital between 1980-1990. Surgery was comprised of mastectomy in 64% of patients, breast conservation in 35% of patients, and was unknown in 1% of patients. Two hundred two patients received concurrent CMF/RT that was defined as an overlap in CMF and RT administration of at least 21 days. Forty-seven patients received sequential CMF/RT (defined as no overlap or an overlap of < 7 days in CMF and RT administration). Other patients received CMF alone. Adverse effects of RT were graded retrospectively using the Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) system. Reasons for interruption or failure to complete RT were recorded. The magnitude of chemotherapy dose reductions and delays also were noted. RESULTS: The median age of the patients was 44 years (range, 26-68 years) and 88% of the patients had lymph node-positive disease. RT was interrupted or discontinued due to side effects in 4% of patients (95% confidence interval [95% CI], 1.7-7.7%) and 0% (95% CI, 0-7.6%), respectively, of the concurrent and sequential groups (P = 0.36). The incidence of Grade 3 or Grade 4 RT toxicity was 1.5% (95% CI, 0.3-4.3%) and 2.1% (95% CI, 0.1-11.3%), respectively, for the concurrent and sequential groups (P = 0.57). The median relative dose intensity of chemotherapy for patients receiving concurrent CMF/RT, sequential CMF/RT, and CMF alone was 0.87, 0.84, and 0.85, respectively (P = 0.22). CONCLUSIONS: The results of the current study demonstrate that the concurrent administration of CMF and RT is associated with a low risk of serious toxicity and is an acceptable adjuvant regimen for patients with breast carcinoma.