Rectal bleeding after hypofractionated radiotherapy for prostate cancer: correlation between clinical and dosimetric parameters and the incidence of grade 2 or worse rectal bleeding

PURPOSE: To investigate the incidence and severity of rectal bleeding after high-dose hypofractionated radiotherapy (RT) for prostate cancer, and to explore the factors affecting the incidence of Grade 2 or worse rectal bleeding. METHODS AND MATERIALS: The data of 52 patients who had been treated by external beam RT for localized prostate cancer between 1999 and 2002 were analyzed. All the patients had received hypofractionated external beam RT to a total dose of 69 Gy in 3-Gy fractions, three fractions weekly. The clinical and dosimetric factors affecting the incidence of Grade 2 or worse late rectal bleeding were analyzed by univariate and multivariate analyses. The effect of the percentage of the whole rectal volume receiving 30%, 50%, 80%, and 90% of the prescribed radiation dose (V(30), V(50), V(80), and V(90), respectively) on the incidence of rectal bleeding was evaluated. RESULTS: Of the 52 patients, 13 (25%) developed Grade 2 or worse rectal bleeding. One patient who needed laser coagulation and blood transfusion for the treatment of rectal bleeding was classified as having Grade 3 rectal bleeding. The median time to the development of Grade 2 or worse rectal bleeding was 11 months. The results of the univariate analysis revealed that the presence of a history of diabetes mellitus (p < 0.001), and V(30) >/= 60%, V(50) >/= 40% (p < 0.05), V(80) >/= 25%, and V(90) >/= 15% (p < 0.001) were statistically significant risk factors for the occurrence of Grade 2 or worse rectal bleeding. The results of the multivariate analysis revealed that a history of diabetes mellitus was the most statistically significant risk factor for the occurrence of rectal bleeding after hypofractionated RT for prostate cancer (p < 0.05). CONCLUSION: A history of diabetes mellitus was the most statistically significant risk factor for the occurrence of Grade 2 or worse rectal bleeding after high-dose hypofractionated RT, although dosimetric factors were also closely associated with the risk of rectal bleeding.     

Dosimetric and Clinical Predictors of Acute Esophagitis in Lung Cancer Patients in Turkey Treated with Radiotherapy

Background: The purpose of this study was to determine the clinical and dosimetric factors associated withacute esophagitis (AE) in lung cancer patients treated with conformal radiotherapy (RT) in Turkey. Materialsand Methods: In this retrospective review 104 lung cancer patients were examined. Esophagitis grades wereverified weekly during treatment, and at 1 week, and 1 and 2 months afterwards. The clinical parametersincluded patient age, gender, tumor pathology, number of chemotherapy treatments before RT, concurrentchemotherapy, radiation dose, tumor response to RT, tumor localization, interruption of RT, weight loss, tumorand nodal stage and tumor volume. The following dosimetric parameters were analyzed for correlation of AE:The maximum (Dmax) and mean (Dmean) doses delivered to the esophagus, the percentage of esophagus volumereceiving ≥10 Gy (V10), ≥20 Gy (V20), ≥30 Gy (V30), ≥35 Gy (V35), ≥40 Gy (V40), ≥45 Gy (V45), ≥50 Gy (V50) and ≥60Gy (V60). Results: Fifty-five patients (52.9%) developed AE. Maximum grades of AE were recorded: Grade 1 in51 patients (49%), and Grade 2 in 4 patients (3.8%). Clinical factors had no statistically significant influence onthe incidence of AE. In terms of dosimetric findings, correlation analyses demonstrated a significant associationbetween AE and Dmax (>5117 cGy), Dmean (>1487 cGy) and V10-60 (percentage of volume receiving >10 to 60 Gy).The most significant relationship between RT and esophagitis were in Dmax (>5117 cGy) (p=0.002) and percentageof esophageal volume receiving >30 Gy (V30>31%) (p=0.008) in the logistic regression analysis. Conclusions: Themaximum dose esophagus greater than 5117 cGy and approximately one third (31%) of the esophageal volumereceiving >30 Gy was the most statistically significant predictive factor associated with esophagitis due to RT.     

Poor predictive value of intraoperative real-time dosimetry for prostate seed brachytherapy

PURPOSE: To identify dosimetric parameters predictive of a good prostate seed I(125) quality implant. We analyzed preimplant and postimplant realtime dosimetry in patients treated with intraoperative (IO) inverse planning. METHODS AND MATERIALS: We analyzed 127 consecutively treated patients with primarily low-risk prostate carcinoma who underwent prostate permanent seed I(125) brachytherapy using an IO planning approach. The implant was done using the three-dimensional transrectal ultrasound (PRE-TRUS)-guided IO interactive inverse preplanning system. The TRUS was repeated in the operating room after the implant procedure was complete (POST-TRUS). The prostate was recontoured and postimplant dosimetry was calculated. Each patient underwent computed tomography scan on Day 28 (CT-D28) to evaluate implant quality. Area under the receiver operating characteristic curves (AUROC) was evaluated for models predictive of a V100 of >/=90% and a D90 of >/=140 Gy on the basis of CT-D28 values. RESULTS: On CT-D28, 72.4% of patients had a V100 of >/=90% and 74.8% had a D90 of >/=140 Gy. AUROC for a V100 of >/=90% was 0.665 (p = 0.004) on PRE-TRUS and 0.619 (p = 0.039) on POST-TRUS. AUROC for D90 of >/=140 Gy was 0.602 (p = 0.086) on PRE-TRUS and 0.614 (p = 0.054) on POST-TRUS. Using PRE-TRUS V100 cutoff of >97% gives sensitivity of 88% and a false-positive rate of 63%. A POST-TRUS D90 cutoff of >170 Gy resulted in a sensitivity of 62% and a false-positive rate of 34%. CONCLUSIONS: Because of unacceptably high false-positive rates, IO preimplant and postimplant TRUS-based dosimetry are not accurate tools to predict for postimplant computed tomography-based dosimetry.     

三维适形放射治疗局部晚期肺癌所致急性食管损伤相关因素分析

 目的 探讨三维适形放射治疗局部晚期中央型非小细胞肺癌所致急性食管损伤相关因素分析。方法 2002年8月-2005年10月，76例NSCLC患者接受三维适形放射治疗，对三维适形计划及患者临床资料进行单因素、多因素分析，评价食管损伤。结果 76例NSCLC中，共发生急性食管炎27例．Ⅰ级15例、Ⅱ级6例、Ⅲ级6例。相关分析显示与急性食管炎相关的因素有食管V50食管所受平均剂量、同期化疗。Logistic多元回归结果显示急性放射性食管炎发生的影响因素为化疗、食管V50（OR值分别为3．193，1．034）。结论 三维适形放射治疗局部晚期中央型非小细胞肺癌时放射所致急性食管损伤与放化疗同期进行和食管V50明显相关。     

Risk factors of late rectal bleeding after carbon ion therapy for prostate cancer

PURPOSE: The aim of this study was to determine the risk factors for late gastrointestinal (GI) morbidity after hypofractionated carbon ion radiotherapy (C-ion RT) for prostate cancer. METHODS AND MATERIALS: Between April 2000 and November 2003, a Phase II clinical trial of C-ion RT with a total dose of 66 GyE in 20 fractions was performed on 175 patients with prostate cancer, and the correlations of clinical and dosimetric parameters with the incidence of late GI toxicity in 172 patients who survived for more than 18 months were investigated. RESULTS: Although no Grade 3-4 late morbidities of the rectum were observed, Grade 1 and 2 morbidities developed in 23 (13%) and 4 (2%) patients, respectively. Dose-volume histogram analysis revealed that the percentage of rectal volume receiving 50% of the prescribed dose (V50) was significantly higher in patients with rectal toxicity than without toxicity (13.2 +/- 5.6% with toxicity; 11.4 +/- 4.0% without toxicity, p = 0.046). Multivariate analysis demonstrated that the use of anticoagulation therapy (p = 0.010) and rectal V50 (p = 0.012) were significant risk factors for the occurrence of Grade 1-2 late GI toxicity. CONCLUSIONS: Although C-ion RT with hypofractionation yielded favorable results regarding late GI complication, dosimetric parameter was a very important factor in the occurrence of rectal bleeding after C-ion RT as well as photon beam RT. Our results provide useful information for physicians applying charged particle RT in the treatment of prostate cancer.     

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.     

适形放疗晚期肺癌放射性食管炎相关因素分析

目的分析Ⅲ～Ⅳ期非小细胞肺癌三维适形放射治疗中急性放射性食管损伤（AE）的发生率及其相关因素。方法选择2006年3月至2008年11月行三维适形放疗的晚期肺癌患者195例,男165例,女30例。其中有79例患者行同步放化疗,中位等效生物剂量为72.0Gy,观察AE的发生率,采用单因素和多因素变量分析方法,对选择的临床和剂量学因素进行与2级以上AE的相关性分析。结果 2级AE38例（19.5%）,3级AE25例（12.8%）。单变量分析显示,临床因素中疗前体重下降≥5%、同时化放疗、淋巴结分期、临床类型和后程超分割放疗与2级以上AE有相关性,剂量学指标中食管受照最大剂量、平均剂量、V20、V25、V30、V35、V40、V45、V50、V55、V60的差异均有统计学意义（P〈0.001）,同时放化疗和V55在BinaryLogistic多因素分析中的差异有统计学意义。结论期非小细胞肺癌三维适形放射治疗中,同时化放疗和V55是预测AE最有价值的指标。     

适形放疗晚期肺癌放射性食管炎相关因素分析

目的分析Ⅲ~Ⅳ期非小细胞肺癌三维适形放射治疗中急性放射性食管损伤(AE)的发生率及其相关因素。方法选择2006年3月至2008年11月行三维适形放疗的晚期肺癌患者195例,男165例,女30例。其中79例患者行同步放化疗,中位等效生物剂量为72.0 Gy,观察AE的发生率,采用单因素和多因素变量分析方法,对选择的临床和剂量学因素进行与2级以上AE的相关性分析。结果 2级AE 38例(19.5%),3级AE 25例(12.8%)。单变量分析显示,临床因素中疗前体重下降≥5%、同时化放疗、淋巴结分期、临床类型和后程超分割放疗与2级以上AE有相关性,剂量学指标中食管受照最大剂量、平均剂量、V20、V25、V30、V35、V40、V45、V50、V55、V60的差异均有统计学意义(P<0.001),同时放化疗和V55在Binary Logistic多因素分析中的差异有统计学意义。结论Ⅲ~Ⅳ期非小细胞肺癌三维适形放射治疗中,同时化放疗和V55是预测AE最有价值的指标。     

Initial evaluation of treatment-related pneumonitis in advanced-stage non-small-cell lung cancer patients treated with concurrent chemotherapy and intensity-modulated radiotherapy

PURPOSE: To investigate the rate of high-grade treatment-related pneumonitis (TRP) in patients with advanced non-small-cell lung cancer (NSCLC) treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: From August 2002 to August 2005, 151 NSCLC patients were treated with IMRT. We excluded patients who did not receive concurrent chemotherapy or who had early-stage cancers, a history of major lung surgery, prior chest RT, a dose <50 Gy, or IMRT combined with three-dimensional conformal RT (3D-CRT). Toxicities were graded by Common Terminology Criteria for Adverse Events version 3.0. Grade > or = 3 TRP for 68 eligible IMRT patients was compared with TRP among 222 similar patients treated with 3D-CRT. RESULTS: The median follow-up durations for the IMRT and 3D-CRT patients were 8 months (range, 0-27 months) and 9 months (range, 0-56 months), respectively. The median IMRT and 3D-CRT doses were 63 Gy. The median gross tumor volume was 194 mL (range, 21-911 mL) for IMRT, compared with 142 mL (range, 1.5-1,186 mL) for 3D-CRT (p = 0.002). Despite the IMRT group's larger gross tumor volume, the rate of Grade > or = 3 TRP at 12 months was 8% (95% confidence interval 4%-19%), compared with 32% (95% confidence interval 26%-40%) for 3D-CRT (p = 0.002). CONCLUSIONS: In advanced NSCLC patients treated with chemoradiation, IMRT resulted in significantly lower levels of Grade > or = 3 TRP compared with 3D-CRT. Clinical, dosimetric, and patient selection factors that may have influenced rates of TRP require continuing investigation. A randomized trial comparing IMRT with 3D-CRT has been initiated.     

Feasibility of proton beam therapy for reirradiation of locoregionally recurrent non-small cell lung cancer

Background and purpose

Options are limited for patients with intrathoracic recurrence of non-small cell lung cancer (NSCLC) who previously received radiation. We report our 5-year experience with the toxicity and efficacy of proton beam therapy (PBT) for reirradiation.

Materials and methods

Thirty-three patients underwent PBT reirradiation for intrathoracic recurrent NSCLC at a single institution. All patients had had RT for NSCLC (median initial dose 63 Gy in 33 fractions), with median interval to reirradiation of 36 months. Median reirradiation dose was 66 Gy (RBE) in 32 fractions. Toxicity was scored with CTCAE v4.0, and survival outcomes were estimated using Kaplan–Meier.

Results

Thirty-one patients (94%) completed reirradiation. At a median 11 months’ follow-up, 1-year rates of overall survival, progression-free survival, locoregional control, and distant metastasis-free survival were 47%, 28%, 54%, and 39%. Rates of severe (grade ?3) toxicity were 9% esophageal, 21% pulmonary; 1 patient had grade 4 esophagitis, and 2 had grade 4 pulmonary toxicity. Nine patients experienced a second in-field failure.

Conclusions

PBT is an option for treating recurrent NSCLC. However, the rates of locoregional recurrence and distant metastasis are high and the potential for toxicity significant. The risks and benefits of PBT must be carefully weighed in each case.     

Dose-volumetric parameters of acute esophageal toxicity in patients with lung cancer treated with three-dimensional conformal radiotherapy

PURPOSE: To retrospectively evaluate which dose-volumetric parameters are associated with the risk of > or = Grade 3 acute esophageal toxicity (AET) in lung cancer patients treated with three-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS: One hundred twenty-four lung cancer patients treated curatively with 3D-CRT were retrospectively analyzed. All patients received conventionally fractionated radiotherapy (RT) with median dose of 60 Gy (range, 54-66 Gy) delivered in 30 fractions (range, 27-33 fractions). Thirty-one patients underwent curative surgery before RT. Ninety-two patients received chemotherapy (induction, 18; concurrent +/- induction, 74). Acute esophageal toxicity was scored by Radiation Therapy Oncology Group criteria. The parameters analyzed included sex; age; Karnofsky performance score; weight loss; surgery; concurrent chemotherapy; the percentages of organ volume receiving > or =20 Gy (V20), > or =30 Gy (V30), > or =40 Gy (V40), > or =50 Gy (V50), > or =55 Gy (V55), > or = 58 Gy (V58), > or =60 Gy (V60), and > or =63 Gy (V63); the percent and absolute length of the esophagus irradiated; the maximum and mean dose to the esophagus; and normal tissue complication probability. RESULTS: Of the 124 patients, 15 patients (12.1%) had Grade 3 AET, and 1 (0.8%) patient had Grade 4 AET. There was no fatal Grade 5 AET. In univariate and multivariate logistic regression analyses, concurrent chemotherapy and V60 were significantly associated with the development of severe (> or = Grade 3) AET (p < 0.05). Severe AET was observed in 15 of 74 patients (20.3%) who received concurrent chemotherapy, and in 1 of 50 patients (2.0%) who did not (p = 0.002). Severe AET was observed in 5 of 87 patients (5.7%) with V60 < or = 30% and in 11 of 37 patients (29.7%) with V60 > 30% (p < 0.001). Among 50 patients who did not receive concurrent chemotherapy, severe AET was observed in 0 of 43 patients (0%) with V60 < or = 30% and in 1 of 7 patients (14.2%) with V60 > 30% (p = 0.140). Among 74 patients who received concurrent chemotherapy, severe AET was observed in 5 of 44 patients (11.4%) with V60 < or = 30% and in 10 of 30 patients (33.3%) with V60 > 30% (p = 0.037). CONCLUSIONS: Concurrent chemotherapy and V60 were associated with the development of severe AET > or = Grade 3. For patients being treated with concurrent chemotherapy, V60 is considered to be a useful parameter predicting the risk of severe AET after conventionally fractionated 3D-CRT for lung cancer.     

Effects of radiotherapy and chemotherapy on lung function in patients with non-small-cell lung cancer

PURPOSE: To evaluate the effects of chemoradiation on objective tests of pulmonary function. MATERIALS AND METHODS: One hundred lung cancer patients treated in five protocols between 1992 and 2000 with combinations of thoracic radiotherapy (RT) and chemotherapy were evaluated with pre- and post-RT pulmonary function tests. The pulmonary function tests were analyzed for changes in measures of obstruction (forced expiratory volume in 1 s per unit of vital capacity [FEV(1)/VC]), restriction (total lung capacity [TLC]), and diffusing capacity (diffusing capacity for carbon monoxide [DLCO]). The use and timing of chemotherapy and RT, as well as patient, tumor, and treatment factors, were evaluated using univariate and multivariate analyses. RESULTS: No treatment or patient factors were significantly associated with changes in FEV(1)/VC. Chemotherapy with RT, compared with RT alone, was associated with a lower post-RT TLC (92% vs. 107%, p = 0.002). Nodal status (N2-N3 vs. N1), tumor location (central vs. peripheral), use of >/=6 treatment fields, and tumor volume >/=100 cm(3) were also associated with a significantly lower post-RT TLC. On univariate analysis, the use of any chemotherapy (p = 0.029) and the use of concurrent vs. sequential chemotherapy (p = 0.028) were predictive of a lower post-RT DLCO. Patient age >/=60 years, nodal status (N2-N3 vs. N0-N1), tumor volume >/=100 cm(3), tumor location (central vs. peripheral), and use of >/=6 treatment fields were also associated with a significantly lower post-RT DLCO. The fractional volume of irradiated normal lung correlated with the decrease in DLCO (p <0.001), with a 1.3% DLCO decline for each 1% of total lung volume that received >20 Gy. CONCLUSIONS: The addition of chemotherapy to RT significantly exacerbates the post-RT decrease in TLC and DLCO. The greatest decrease in DLCO occurs in patients treated with concurrent chemoradiation.     

Dose and volume reduction for normal lung using intensity-modulated radiotherapy for advanced-stage non-small-cell lung cancer

PURPOSE: To investigate dosimetric improvements with respect to tumor-dose conformity and normal tissue sparing using intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3D-CRT) for advanced-stage non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Forty-one patients with Stage III-IV and recurrent NSCLC who previously underwent 3D-CRT were included. IMRT plans were designed to deliver 63 Gy to 95% of the planning target volume using nine equidistant coplanar 6-MV beams. Inverse planning was performed to minimize the volumes of normal lung, heart, esophagus, and spinal cord irradiated above their tolerance doses. Dose distributions and dosimetric indexes for the tumors and critical structures in both plans were computed and compared. RESULTS: Using IMRT, the median absolute reduction in the percentage of lung volume irradiated to >10 and >20 Gy was 7% and 10%, respectively. This corresponded to a decrease of >2 Gy in the total lung mean dose and of 10% in the risk of radiation pneumonitis. The volumes of the heart and esophagus irradiated to >40-50 Gy and normal thoracic tissue volume irradiated to >10-40 Gy were reduced using the IMRT plans. A marginal increase occurred in the spinal cord maximal dose and lung volume >5 Gy in the IMRT plans, which could be have resulted from the significant increase in monitor units and thus leakage dose in IMRT. CONCLUSION: IMRT planning significantly improved target coverage and reduced the volume of normal lung irradiated above low doses. The spread of low doses to normal tissues can be controlled in IMRT with appropriately selected planning parameters. The dosimetric benefits of IMRT for advanced-stage non-small-cell lung cancer must be evaluated further in clinical trials.     

Multi-Institutional Prospective Study of Reirradiation with Proton Beam Radiotherapy for Locoregionally Recurrent Non–Small Cell Lung Cancer

ObjectivesThe management of recurrent NSCLC in the setting of prior radiation therapy is challenging. Proton radiotherapy (PRT) is ideally suited to minimize toxicity to previously irradiated organs. We report the safety/feasibility of PRT for NSCLC reirradiation in a prospective multi-institutional study.Materials and MethodsBetween October 2010 and December 2015, 57 patients with recurrent NSCLC in or near their prior radiation field were treated at three proton centers. Patients were classified by tumor volume, location, and clinical characteristics. Toxicities were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Survival outcomes were estimated by using Kaplan-Meier analysis.ResultsFifty-two patients (93%) completed the reirradiation course. Their median age was 65 years (41–86). Patients with high tumor volume (clinical target volume–to–internal target volume ratio ≥250 cm³) were closed to enrollment owing to infeasibility in August 2012. Concurrent systemic therapy was delivered to 67% of patients. Fourteen patients (25%) had evidence of local (n = 9) or regional (n = 5) recurrence. Distant metastases after reirradiation developed in six patients (11%). The 1-year rates of overall and progression-free survival were 59% and 58%, respectively. In total, grade 3 or higher acute and/or late toxicity developed in 24 patients (42%), acute toxicity developed in 22 (39%), and late toxicity developed in seven (12%). Six grade 5 toxicities were observed. Increased overlap with the central airway region, mean esophagus and heart doses, and concurrent chemotherapy were associated with significantly higher rates of grade 3 or higher toxicity. Decreased overall survival was seen with increased mean esophagus dose (p = 0.007).ConclusionsIn this prospective study, PRT for recurrent NSCLC is feasible but can be associated with significant toxicity. Providers should remain cautious in reirradiating NSCLC, paying close consideration to tumor volume, location, and relevant dosimetric parameters. Further research is needed for optimal patient selection to improve overall outcomes.     

Dosimetric correlates for acute esophagitis in patients treated with radiotherapy for lung carcinoma

PURPOSE: Acute esophagitis is a common complication of radiotherapy (RT) for non-small-cell carcinoma of the lung. Previous reports have related esophagitis to dosimetric parameters such as the length of the irradiated esophagus, maximal dose, or volume of the organ treated beyond a threshold dose. However, when using oblique beams, a portion of the esophageal circumference may be outside the treated field, resulting in partial esophageal irradiation. Therefore, our aim was to determine whether the irradiated esophageal surface area and/or esophageal volume are predictive of acute esophagitis in relation to other clinical and treatment-related factors. METHODS AND MATERIALS: Complete dose-volume information was gathered for 166 patients receiving definitive RT for Stage I-IIIB non-small-cell carcinoma of the lung at our institution. Seventy-eight patients received chemotherapy (37 before RT and 41 concurrently). All patients were treated to doses of 60-74 Gy (median, 70 Gy) delivered in single daily fractions of 1.8-2.1 Gy. The doses were prescribed to the isocenter without using heterogeneity corrections; however, the doses were corrected to account for lung heterogeneity in this report. Esophageal contrast was used to contour the esophagus from the cricoid to the gastroesophageal junction in each case. Esophagitis was scored according to the Radiation Therapy Oncology Group criteria with Grade 2 or worse considered clinically significant. To determine the importance of the irradiated surface area, the volumetric treatment plan for each patient was prepared for analysis by relating a surface area to each point of the esophagus contour. Spearman's rank correlation was used to correlate the esophagitis score with A(d), where A represents the surface area (in centimeters squared) receiving the dose, d, or greater (in Gray), or V(d), where V represents the volume (in centimeters cubed) receiving d (in Gray). The surface areas studied were A(5)-A(80) or V(5)-V(80) in 5-Gy increments. The clinical parameters studied in univariate analysis included patient age, stage, performance status, use of pretreatment chemotherapy, and use of concurrent chemotherapy. Step-wise regression analysis was then used to determine the statistically significant factors predicting acute esophagitis. RESULTS: Forty-five patients (27%) developed Grade 2 or worse esophagitis, 37 developed Grade 2, 7 Grade 3, and 1 Grade 4. No deaths resulted from this complication. The most statistically significant single parameters for predicting acute esophagitis were A(55), V(60), and the use of concurrent chemotherapy. Age, stage, performance status, and pre-RT chemotherapy had no statistically significant influence on the incidence of acute esophagitis. On logistic regression analysis, A(55) (p < or =0.0005), V(60) (p < or =0.001), and the use of concurrent chemotherapy (p = 0.001) emerged as statistically significant correlates of acute esophagitis. CONCLUSION: The esophageal surface area receiving > or =55 Gy, the esophageal volume receiving > or =60 Gy, and the use of concurrent chemotherapy were the most statistically significant predictive factors for early esophagitis. Adequate dosimetric coverage of the planning target volume remains the goal of RT planning. High values of A(55) and/or V(60) are indicative of the development of acute esophagitis and may indicate a need to explore alternative RT planning options.     

PET/CT对非小细胞肺癌三维适形放疗中治疗计划参数的影响

目的:观察PET/CT对非小细胞肺癌(NSCLC)三维适形放疗(3D-CRT)中治疗计划参数的影响.方法:对83例在PET/CT定位下拟行根治性3D-CRT的NSCLC患者,分别以CT图像和PET/CT融合图像勾画大体肿瘤靶区(GTVCT和GTVPET/CT),分别制定放疗计划,并对两者进行比较.结果:PET/CT明显改变44例(53.01％)患者GTV或PTV,31例PTV和(或)GTV减小,13例PTV和(或)GTV增加.根据PET/CT和CT分别制定的放疗计划在VGTV、VE50、SCM和ESM的差异有统计学意义,P值分别为0.001、0.001、0.000和0.002.结论:应用PET/CT制定NSCLC3D-CRT治疗计划可降低食管和脊髓的受照射剂量,从而有利于放疗剂量的提升.     

Increased therapeutic ratio by 18FDG-PET CT planning in patients with clinical CT stage N2-N3M0 non-small-cell lung cancer: a modeling study

PURPOSE: With this modeling study, we wanted to estimate the potential gain from incorporating fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning in the radiotherapy treatment planning of CT Stage N2-N3M0 non-small-cell lung cancer (NSCLC) patients. METHODS AND MATERIALS: Twenty-one consecutive patients with clinical CT Stage N2-N3M0 NSCLC were studied. For each patient, two three-dimensional conformal treatment plans were made: one with a CT-based planning target volume (PTV) and one with a PET-CT-based PTV, both to deliver 60 Gy in 30 fractions. From the dose-volume histograms and dose distributions on each plan, the dosimetric factors predicting esophageal and lung toxicity were analyzed and compared. For each patient, the maximal tolerable prescribed radiation dose for the CT PTV vs. PET-CT PTV was calculated according to the constraints for the lung, esophagus, and spinal cord. From these results, the tumor control probability (TCP) was estimated, assuming a clinical dose-response curve with a median toxic dose of 84.5 Gy and a gamma(50) of 2.0. Dose-response curves were modeled, taking into account geographic misses according to the accuracy of CT and PET in our institutions. RESULTS: The gross tumor volume of the nodes decreased from 13.7 +/- 3.8 cm(3) on the CT scan to 9.9 +/- 4.0 cm(3) on the PET-CT scan (p = 0.011). All dose-volume characteristics for the esophagus and lungs decreased in favor of PET-CT. The esophageal V(45) (the volume of the esophagus receiving 45 Gy) decreased from 45.2% +/- 4.9% to 34.0% +/- 5.8% (p = 0.003), esophageal V(55) (the volume of the esophagus receiving 55 Gy) from 30.6% +/- 3.2% to 21.9% +/- 3.8% (p = 0.004), mean esophageal dose from 29.8 +/- 2.5 Gy to 23.7 +/- 3.1 Gy (p = 0.004), lung V(20) (the volume of the lungs minus the PTV receiving 20 Gy) from 24.9% +/- 2.3% to 22.3% +/- 2.2% (p = 0.012), and mean lung dose from 14.7 +/- 1.3 Gy to 13.6 +/- 1.3 Gy (p = 0.004). For the same toxicity levels of the lung, esophagus, and spinal cord, the dose could be increased from 56.0 +/- 5.4 Gy with CT planning to 71.0 +/- 13.7 Gy with PET planning (p = 0.038). The TCP corresponding to these doses was estimated to be 14.2% +/- 5.6% for CT and 22.8% +/- 7.1% for PET-CT planning (p = 0.026). Adjusting for geographic misses by PET-CT vs. CT planning yielded TCP estimates of 12.5% and 18.3% (p = 0.009) for CT and PET-CT planning, respectively. CONCLUSION: In this group of clinical CT Stage N2-N3 NSCLC patients, use of FDG-PET scanning information in radiotherapy planning reduced the radiation exposure of the esophagus and lung, and thus allowed significant radiation dose escalation while respecting all relevant normal tissue constraints. This, together with a reduced risk of geographic misses using PET-CT, led to an estimated increase in TCP from 13% to 18%. The results of this modeling study support clinical trials investigating incorporation of FDG-PET information in CT-based radiotherapy planning.     

Prostate seed implantation using 3D-computer assisted intraoperative planning vs. a standard look-up nomogram: Improved target conformality with reduction in urethral and rectal wall dose

PURPOSE: To compare dosimetric outcomes between two real-time prostate seed implantation (PSI) techniques to evaluate the impact of three-dimensional (3D) intraoperative computer planning on target coverage, conformality, and preset urethral and rectal dose constraints. METHODS AND MATERIALS: One hundred and fourteen patients with clinically localized prostate cancer underwent ultrasound-guided transperineal PSI of the prostate with (125)I sources as monotherapy. From 1999 to 2001, 69 patients were implanted in real-time using a standard look-up nomogram (Group 1: NG-PSI). All patients were implanted with a modified peripheral loading technique in which 75-80% of the calculated total activity was delivered to the gland periphery, with the remaining 20-25% activity placed in the gland interior, to achieve a prescribed dose (PD) of 144 Gy to cover the gland with acceptable homogeneity. No preoperative or intraoperative planning was performed to set dose constraints to the urethra or anterior rectal wall. Dosimetric outcome from this group was compared with 45 patients subsequently implanted after 2001 using an intraoperative 3D computer planning system (Group 2: 3D-PSI). A similar modified peripheral loading technique was used as an option in the planning system. Preoperative dose constraints were placed on the urethra (V150 < 35%), prostate (V100 > 95% of PD; D90: 140-180 Gy), and rectal wall (V110 < 1.5 cc) with real-time dosimetric feedback performed after peripheral loading. Manual dose optimization was performed to determine interior needle position and remaining number and placement of (125)I sources to adhere to urethral and rectal constraints and target coverage goals. Both groups underwent postimplant CT analysis to determine dosimetric outcome with regard toV100(prostate), D90(prostate), V150(urethra), and V110(rectum). Univariate and multivariate analysis was performed to determine variables impacting on dosimetric outcome. RESULTS: Analysis of preimplant and postimplant variables demonstrated no difference in the median preimplant gland volume (33 cc vs. 35 cc; p = 0.31), median mCi/seed strengths (0.4 vs. 0.45 mCi; p = 0.23), median V100 (94% vs. 94%), or median D90 at postimplant Day 30 (165 Gy vs. 160 Gy; p = 0.26) between Groups 1 and 2. However, for Group 2 (3D-PSI) the median total mCi implanted (26 vs. 33 mCi; p < 0.0001) and the median number of seeds implanted (67 vs. 83; p < 0.0001) were reduced substantially. The percent of patients exceeding a D90 > 180 Gy was reduced from 29% in Group 1 to 16% in Group 2 (p = 0.08). A reduction was observed in the percent of patients receiving a D90 < 140 Gy (14% Group 1 vs. 9% Group 2, p = 0.56). The median V150(urethra) for Group 2 was reduced dramatically with 3D-PSI compared with NG-PSI (63% vs. 17%; p < 0.0001). A V150(urethra) > 30% was observed in 88% in Group 1 compared with 29% in Group 2, p < 0.0001. Similarly, the median V110(rectum) for Group 1 was significantly higher than that in Group 2 (1.93 vs. 0.26 cc; p < 0.0001). The percent of patients with V110(rectum) > 1.5 cc in Group 1 and Group 2 was 57% and 13%, respectively (p < 0.0001). CONCLUSIONS: The adoption of 3D computer intraoperative dose planning and optimization for prostate seed implantation resulted in dramatic reductions in urethral and rectal wall doses, while consistently producing excellent target coverage with reduced dose variability above 180 Gy and below 140 Gy, compared with the use of a standard look-up nomogram. Additionally, the reduction in total mCi and number of seeds needed to achieve improved conformality was substantial and may have implications for cost savings.