Kayoko Tsujino

Predictive value of dose-volume histogram parameters for predicting radiation pneumonitis after concurrent chemoradiation for lung cancer.

PURPOSE To clarify whether the percentage of pulmonary volume irradiated to >20 Gy (V20) is related to the incidence and grade of radiation pneumonitis (RP) in cases of lung cancer treated with concurrent chemoradiation. METHODS AND MATERIALS The subjects comprised 71 patients with lung cancer who were treated with conventionally fractionated definitive concurrent chemoradiation. The chemotherapy agents were carboplatin or cisplatin combined with taxane for most patients. Radiotherapy was delivered at 1.8-2.0 Gy fractions once daily to a total of 48-66 Gy (median 60). We analyzed the relation between RP grade and V20. Univariate and multivariate analyses were performed to assess patient- and treatment-related factors, including age, gender, smoking history, pulmonary function (forced expiratory volume in 1 s), tumor location (upper lobe vs. middle/lower lobe), chemotherapy regimen (platinum + taxane vs. other), total dose, overall radiation periods in addition to V20. RESULTS With a median follow-up of 7.5 months, an RP grade of 0, 1, 2, 3, and 5 was observed in 16, 35, 17, 1, and 2 patients, respectively; the corresponding mean V20 values were 20.1%, 22.0%, 26.3%, 27.0%, and 34.5%. The 6-month cumulative incidence of RP greater than Grade 2 was 8.7%, 18.3%, 51%, and 85% in patients with a V20 of <or=20%, 21-25%, 26-30%, and >or=31%, respectively (p <0.0001). According to both univariate and multivariate analyses, V20 was the only factor associated with RP of Grade 2 or greater. CONCLUSION The incidence and grade of RP are significantly related to the V20 value. Thus, V20 appears to be a factor that can be used to predict RP after concurrent chemoradiation for lung cancer.

Predicting Radiation Pneumonitis After Chemoradiation Therapy for Lung Cancer: An International Individual Patient Data Meta-analysis

BACKGROUND Radiation pneumonitis is a dose-limiting toxicity for patients undergoing concurrent chemoradiation therapy (CCRT) for non-small cell lung cancer (NSCLC). We performed an individual patient data meta-analysis to determine factors predictive of clinically significant pneumonitis. METHODS AND MATERIALS After a systematic review of the literature, data were obtained on 836 patients who underwent CCRT in Europe, North America, and Asia. Patients were randomly divided into training and validation sets (two-thirds vs one-third of patients). Factors predictive of symptomatic pneumonitis (grade ≥2 by 1 of several scoring systems) or fatal pneumonitis were evaluated using logistic regression. Recursive partitioning analysis (RPA) was used to define risk groups. RESULTS The median radiation therapy dose was 60 Gy, and the median follow-up time was 2.3 years. Most patients received concurrent cisplatin/etoposide (38%) or carboplatin/paclitaxel (26%). The overall rate of symptomatic pneumonitis was 29.8% (n=249), with fatal pneumonitis in 1.9% (n=16). In the training set, factors predictive of symptomatic pneumonitis were lung volume receiving ≥20 Gy (V(20)) (odds ratio [OR] 1.03 per 1% increase, P=.008), and carboplatin/paclitaxel chemotherapy (OR 3.33, P<.001), with a trend for age (OR 1.24 per decade, P=.09); the model remained predictive in the validation set with good discrimination in both datasets (c-statistic >0.65). On RPA, the highest risk of pneumonitis (>50%) was in patients >65 years of age receiving carboplatin/paclitaxel. Predictors of fatal pneumonitis were daily dose >2 Gy, V(20), and lower-lobe tumor location. CONCLUSIONS Several treatment-related risk factors predict the development of symptomatic pneumonitis, and elderly patients who undergo CCRT with carboplatin-paclitaxel chemotherapy are at highest risk. Fatal pneumonitis, although uncommon, is related to dosimetric factors and tumor location.

Phase III Study Comparing Second- and Third-Generation Regimens With Concurrent Thoracic Radiotherapy in Patients With Unresectable Stage III Non–Small-Cell Lung Cancer: West Japan Thoracic Oncology Group WJTOG0105

PURPOSE This phase III trial of concurrent thoracic radiotherapy (TRT) was conducted to compare third-generation chemotherapy with second-generation chemotherapy in patients with unresectable stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Eligible patients received the following treatments: A (control), four cycles of mitomycin (8 mg/m(2) on day 1)/vindesine (3 mg/m(2) on days 1, 8)/cisplatin (80 mg/m(2) on day 1) plus TRT 60 Gy (treatment break for 1 week); B, weekly irinotecan (20 mg/m(2))/carboplatin (area under the plasma concentration-time curve [AUC] 2) for 6 weeks plus TRT 60 Gy, followed by two courses of irinotecan (50 mg/m(2) on days 1, 8)/carboplatin (AUC 5 on day 1); C, weekly paclitaxel (40 mg/m(2))/carboplatin (AUC 2) for 6 weeks plus TRT 60 Gy, followed by two courses of paclitaxel (200 mg/m(2) on day 1)/carboplatin (AUC 5 on day 1). RESULTS The median survival time and 5-year survival rates were 20.5, 19.8, and 22.0 months and 17.5%, 17.8%, and 19.8% in arms A, B, and C, respectively. Although no significant differences in overall survival were apparent among the treatment arms, noninferiority of the experimental arms was not achieved. The incidences of grade 3 to 4 neutropenia, febrile neutropenia, and gastrointestinal disorder were significantly higher in arm A than in arm B or C (P < .001). Chemotherapy interruptions were more common in arm B than in arm A or C. CONCLUSION Arm C was equally efficacious and exhibited a more favorable toxicity profile among three arms. Arm C should be considered a standard regimen in the management of locally advanced unresectable NSCLC.

Dosimetric predictors of radiation esophagitis in patients treated for non-small-cell lung cancer with carboplatin/paclitaxel/radiotherapy

PURPOSE To establish dosimetric predictors of radiation esophagitis (RE) in patients treated with a combination of carboplatin, paclitaxel, and radiotherapy. METHODS AND MATERIALS Three-dimensional radiotherapy plans of 26 patients with non-small-cell lung cancer who received 50-60 Gy of radiotherapy concurrently with weekly administration of carboplatin (AUC 2) and paclitaxel (40-45 mg/m(2)) were reviewed in conjunction with RE. The factors analyzed included the following: percentages of organ volumes receiving >40 Gy (V40), >45 Gy (V45), >50 Gy (V50), and >55 Gy (V55); the length of esophagus (total circumference) treated with >40 Gy (LETT40), >45 Gy (LETT45), >50 Gy (LETT50), and >55 Gy (LETT55); the maximum dose in the esophagus (Dmax); and the mean dose in the esophagus (Dmean). Data were obtained on the basis of superposition algorithm. RESULTS All factors except Dmax showed statistical correlation with RE. Good correlations were shown between RE and LETT45 (rho = 0.714) and V45 (rho = 0.686). CONCLUSIONS LETT45 and V45 appear to be useful dosimetric predictors of RE. It is also suggested that Dmax does not predict RE.

Endoscopic findings of radiation esophagitis in concurrent chemoradiotherapy for intrathoracic malignancies

BACKGROUND AND PURPOSE The incidence and extent of radiation esophagitis were assessed endoscopically in patients treated with concurrent chemoradiotherapy. PATIENTS AND METHODS Eighty-two patients who received thoracic radiotherapy for lung, thymic, or esophageal cancer were investigated endoscopically from July 1991 to the end of 1997. Among them, 23 esophageal cancer patients were treated with radiation alone, and the others were treated with concurrent chemoradiotherapy. Esophageal endoscopy was performed during or just after radiotherapy. The presence of radiation esophagitis was assessed and assigned an endoscopic score (i.e. grade 0 for normal, 1 for erythema, 2 for erosion or sloughing, 3 for ulcer, hemorrhage, or stricture). The symptomatic grade was assessed using the RTOG (Radiation Therapy Oncology Group) acute radiation morbidity score. RESULTS A correlation was seen between endoscopic and RTOG scores. However, even some patients with RTOG grade 0 to 1 had endoscopic grade 3 esophagitis. Endoscopic grade 3 was observed in 16 (27.1%) patients in the concurrent chemoradiotherapy group, whereas it did not occur in any patient in the radiation alone group (P=0.004). CONCLUSIONS Our results suggest that (1) RTOG score correlates closely to esophageal mucosal damage, and (2) more severe esophagitis occurs in those undergoing concurrent chemoradiotherapy than those undergoing radiotherapy alone [corrected].

Combined Analysis of V20, VS5, Pulmonary Fibrosis Score on Baseline Computed Tomography, and Patient Age Improves Prediction of Severe Radiation Pneumonitis After Concurrent Chemoradiotherapy for Locally Advanced Non-Small-Cell Lung Cancer

Introduction: We aimed to develop a more accurate model for predicting severe radiation pneumonitis (RP) after concurrent chemoradiotherapy for non–small-cell lung cancer. Methods: We retrospectively analyzed data from 122 patients with locally advanced non–small-cell lung cancer treated with concurrent chemoradiotherapy. Several dose-volume histogram metrics including absolute lung volume spared from a 5 Gy dose (VS5) were analyzed for an association with RP above NCI-CTC grade 3 (RP ≥ G3). Clinical factors including pulmonary fibrosis score (PFS) and pulmonary emphysema score on baseline chest computed tomography (CT) were also analyzed. Results: Fourteen patients (11.4%) developed RP greater than or equal to G3. On univariate analysis, all dose-volume histogram metrics, sex, and PFS on baseline CT were significantly (p < 0.05) associated with occurrence of RP greater than or equal to G3. Multivariate analysis revealed that V20 greater than or equal to 26%, VS5 less than 1500 cc, age greater than or equal to 68 years, and PFS on baseline CT greater than or equal to 2 were significant risk factors. Thus, we defined a new predictive risk score (PRS) that combines these factors. The cumulative incidence of RP greater than or equal to G3 at 12 months were 0%, 7.8%, 26.6%, and 71.4% when the PRS was 0, 3–5, 6–8, and 9–14, respectively (p < 0.001). This PRS was superior at predicting RP than both V20 and VS5 combined, or V20 alone by receiver operating characteristic analysis (area under the curve, 0.888 versus 0.779 versus 0.678). Conclusions: V20, VS5, age, and PFS on baseline CT are independent and significant risk factors for occurrence of severe RP. Combining these factors may improve the predictability of severe RP.

Radiation Therapy in Patients with Implanted Cardiac Pacemakers and Implantable Cardioverter Defibrillators: A Prospective Survey in Japan

Radiotherapy/Pacemaker/ICD/Malfunction. Patients with implanted cardiac pacemakers (ICPs) or implantable cardioverter defibrillators (ICDs) ar e increasing in number, and the incidence of treating these patients with radiation therapy also is increasing. Thus, a prospective survey was conducted of patien ts with these devices receiving radiation therapy. A prospective survey of patients with ICPs or ICDs treated with radiation therapy was conducted on methods of radiation therapy, status of ICP/ICD, and management of patients before, during, and after radiation th erapy. After completion of radiation therapy, study participants were registered via mail, fax, or e-mail. Sixty-two patients from 29 institutions were registered from September 2006 to December 2008. Sixty patients had an ICP and 2 had an ICD. The total dose was estimated before radiation therapy by dosevolume histogram in 26 patients (42%) and by measurement of actual doses in 9 (15%). In one patient, the maximum total dose was 2069 cGy; however, in the other patients, the ICP/ICD dose did not exceed 478 cGy. Function of ICPs and ICDs was checked before radiation therapy in 38 patients (61%), after radiation therapy in 32 (52%), and both before and after radiation ther apy in 29 (47%). ICP malfunction occurred in a patient with prostate cancer treated by intensity-modulated radiation therapy to the prostate. Even when an ICP or ICD is not within the field of radiation, malfunction of the device may still occur. To minimize the risk to patients, precautions must be taken during the planning and administration of radiation therapy.

Subcutaneous fibrosis after whole neck irradiation

PURPOSE To identify the risk factors for moderate to severe subcutaneous fibrosis after whole neck irradiation. MATERIALS AND METHODS We analyzed 233 cases of patients who had undergone whole neck irradiation with 4-MV X-ray or 8-10-MeV electrons, or both, and had been followed with regard to their skin condition for at least 1 year. The prescribed dose to the whole neck ranged from 19.2 to 72.4 Gy (median 50). The skin-absorbed dose was specified as that at a depth of 4.1 mm (d4.1-mm(depth)), and a biologically equivalent dose (BED) of d4.1-mm(depth) was also estimated (BED(1.8) 4.1-mm(depth)). RESULTS Univariate analysis revealed that previous neck dissection, concurrent chemotherapy, corticosteroid administration as a part of chemotherapy, fractionation, and BED(1.8) 4.1-mm(depth) were significant prognostic variables. Multivariate analysis showed that BED(1.8) 4.1-mm(depth) and previous neck dissection were the only prognostic variables for moderate to severe subcutaneous fibrosis. CONCLUSION A high dose to a 4.1-mm depth of the skin and a history of neck dissection were identified as the predominant risk factors for moderate to severe subcutaneous fibrosis after whole neck irradiation. A subcutaneous dose should be considered in radiotherapy treatment planning involving the whole neck, especially in cases in which patients have undergone previous neck dissection.

White matter changes on magnetic resonance imaging following whole-brain radiotherapy for brain metastases

PurposeThe purpose of this study was to evaluate white matter (WM) abnormalities induced by WBRT.Materials and methodsTwenty-four patients (11 men and 13 women; age range 38–74 years, median 60 years) who survived for more than 1 year after completion of WBRT (radiation dose range 30–40 Gy, median 35 Gy) at our institution between January 2000 and June 2003 were followed up with magnetic resonance (MR) scans for 11–51 months (median 19 months). We evaluated WM changes attributable to WBRT as grade 0–6 and assessed possible contributing factors by statistical analysis.ResultsWM changes were found in 20 patients: Eight were assessed as grade 2, three as grade 3, and nine as grade 5. In total, 12 patients developed grade 3 or higher WM changes. Age (<60 vs ≥60 years), sex, radiation dose (≤35 vs >35 Gy), chemotherapy (with CDDP vs without CDDP), biologically effective dose (≤120 vs >120 Gy1), and head width (<16.3 vs ≥16.3 cm) were found not to be relevant to the incidence or severity of the WM changes.ConclusionLong-term survivors who have under-gone WBRT may have a higher incidence of WM abnormalities.

Pelvic insufficiency fracture after definitive radiotherapy for uterine cervical cancer: retrospective analysis of risk factors

The purpose of this study is to determine the incidence, clinical characteristics and risk factors of postradiation pelvic insufficiency fracture (PIF) in women with uterine cervical cancer. We reviewed the medical records of 126 patients who received definitive radiotherapy (RT) for uterine cervical cancer between 2003 and 2009 at our institution. Among them, 99 patients who underwent at least one computed tomography (CT) or magnetic resonance imaging of the pelvis during their follow-up at more than 6 months were included in this analysis. The relationship between the incidence of PIF and several patient- and treatment-related factors was analyzed. The median follow-up period was 21 months. Of the 126 patients, 33 (with a total of 50 lesions) were diagnosed with PIF. The 2-year cumulative incidence was 32%. Univariate analysis showed that age ≥70 years (P= 0.0010), postmenopausal state (P = 0.0013), and lower CT density of bone and bone marrow (P= 0.020) significantly related to PIF. In a multivariate analysis, of the 59 patients whose CT densities were evaluable, lower CT density was the only significant factor associated with PIF (P = 0.0026). In conclusion, postradiation PIFs were detected in a considerable number of patients after definitive RT for cervical cancer. Predisposing factors were older age, postmenopausal state, and decreased density of bone and bone marrow on CT.