Three-dimensional conformal radiation therapy for non-small-cell lung cancer: a phase I/II dose escalation clinical trial

PURPOSE: A prospective Phase I/II dose escalation study was conducted to determine the maximum tolerated dose (MTD) in three-dimensional conformal radiation therapy (3D-CRT) for non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: MTD would be reached via a dose escalation study. After 42 Gy/21 fractions, 4.2 weeks by conventional fractionated irradiation through anteroposterior/posteroanterior fields, the 3D-CRT technique was used as boost. The planned total dose escalation depended on lung volume irradiated. According to the percentage of lung volume receiving >20 Gy, the patients were divided into three subgroups (i.e., <25%, 25%-37%, and >37%). The scheduled dose escalation began with 69 Gy and continued to 78 Gy. The boost doses were delivered at 3 Gy per fraction, once per day, five fractions per week. Each dose level includes 5 patients. Besides radiotherapy, all patients received neoadjuvant and adjuvant chemotherapy with MVP regimen (Mitomycin, Vindesine, cis-platium). The criterion for stopping further dose escalation was > or =20% of patients with > or =RTOG Grade 3 radiation pneumonitis. RESULTS: Between June 1999 and February 2001, 50 patients had been enrolled in this study, including 4 with Stage II disease, 31 with Stage IIIa disease, and 15 with Stage IIIb disease. The dose escalation plan has been completed. All subgroups reached the highest predetermined dose levels (i.e., 78 Gy for the <25% subgroup, 78 Gy for the 25-37% subgroup, and 75 Gy for the >37% subgroup). Although none of the subgroups developed more than 20% of >/=Grade 3 acute pneumonitis, dose escalation was terminated because long-term follow-up was needed to observe late complications. Median follow-up time (MFT) for the entire group was 18 months (6-37 months). The most common acute complication was esophagitis in 56% of patients with RTOG Grade 1-2, and in 4% with Grade 3. Acute radiation pneumonitis developed in 36% of patients with RTOG Grade 1-2. Only 1 patient had Grade 3 pneumonitis, which was in the 25-37% subgroup at 75 Gy. The hematopoietic toxicity appeared in 58% of patients with Grade 1-2, and 8% with Grade 3. As to late complications, only 30% of patients developed pulmonary fibrosis of RTOG Grade 1-2. The median survival time for the entire group was 18 months. Two-year overall survival, locoregional progression-free rate, and distant metastasis rate were 44%, 40%, and 41%, respectively. CONCLUSIONS: Although MFT was 18 months, it had not yet been declared because a longer follow-up was needed to observe the late complications. The 2-year overall survival of 44% was very encouraging and implied that 3D-CRT combined with chemotherapy would improve the outcome for locally advanced NSCLC.     

Final results of a Phase I/II dose escalation trial in non-small-cell lung cancer using three-dimensional conformal radiotherapy

PURPOSE: The aim of this study was to determine the maximum tolerated dose (MTD) delivered within 6 weeks in patients with non-small-cell lung cancer (NSCLC). The impact of tumor volume and delivered dose on failure-free interval (FFI) and overall survival (OS) were also studied. METHODS AND MATERIALS: A Phase I/II trial was performed including inoperable NSCLC patients. According to the relative mean lung dose (rMLD), five risk groups with different starting doses were defined: Group 1, rMLD 0.0 to 0.12; Group 2, rMLD 0.12 to 0.18; Group 3, rMLD 0.18 to 0.24; Group 4, rMLD 0.24 to 0.31; and Group 5, rMLD 0.31 to 0.40. Patients underwent irradiation with 2.25 Gy per fraction and a fixed overall treatment time of 6 weeks. The dose was escalated with 6.75 Gy after 6 months follow-up without dose-limiting toxicity. If more than 30 fractions were prescribed, twice-daily irradiation was performed with at least a 6-h interval. RESULTS: A total of 88 patients were included. Tumor Stage I or II was found in 53%, IIIA in 31%, and IIIB in 17%. The MTD was not achieved in risk Group 1 (reached dose, 94.5 Gy). For risk Groups 2 and 3 the MTD was 81 Gy. The 74.3-Gy dose was determined to be safe for Group 4 and the 60.8-Gy dose for Group 5. In 2 patients (5%) an isolated nodal relapse occurred. Based on multivariable analysis, higher doses significantly increased the FFI (p = 0.02) for the total group. The OS was increased in the lower risk groups (p = 0.05) but not in the higher risk groups (p = 0.4). CONCLUSION: Dose escalation is safe up to 94.5 Gy in 42 fractions in 6 weeks in patients with an MLD 13.6 Gy or less. Higher doses are associated with a better FFI and OS for smaller tumor volumes. Involved-field irradiation results in a low percentage of isolated nodal relapses.     

Dose escalation with three-dimensional conformal radiation therapy affects the outcome in prostate cancer

Purpose: Three-dimensional conformal radiation therapy (3D-CRT) is a technique designed to deliver prescribed radiation doses to localized tumors with high precision, while effectively excluding the surrounding normal tissues. It facilitates tumor dose escalation which should overcome the relative resistance of tumor clonogens to conventional radiation dose levels. The present study was undertaken to test this hypothesis in patients with clinically localized prostate cancer.Methods and Materials: A total of 743 patients with clinically localized prostate cancer were treated with 3D-CRT. As part of a phase I study, the tumor target dose was increased from 64.8 to 81 Gy in increments of 5.4 Gy. Tumor response was evaluated by post-treatment decrease of serum prostate-specific antigen (PSA) to levels of ≤1.0 ng/ml and by sextant prostate biopsies performed ≥2.5 years after completion of 3D-CRT. PSA relapse-free survival was used to evaluate long-term outcome. The median follow-up was 3 years (range: 1–7.6 years).Results: Induction of an initial clinical response was dose-dependent, with 90% of patients receiving 75.6 or 81.0 Gy achieving a PSA nadir ≤1.0 ng compared with 76% and 56% for those treated with 70.2 Gy and 64.8 Gy, respectively (p < 0.001). The 5-year actuarial PSA relapse-free survival for patients with favorable prognostic indicators (stage T1-2, pretreatment PSA ≤10.0 ng/ml and Gleason score ≤6) was 85%, compared to 65% for those with intermediate prognosis (one of the prognostic indicators with a higher value) and 35% for the group with unfavorable prognosis (two or more indicators with higher values) (p < 0.001). PSA relapse-free survival was significantly improved in patients with intermediate and unfavorable prognosis receiving ≥75.6 Gy (p < 0.05). A positive biopsy at ≥2.5 years after 3D-CRT was observed in only 1/15 (7%) of patients receiving 81.0 Gy, compared with 12/25 (48%) after 75.6 Gy, 19/42 (45%) after 70.2 Gy, and 13/23 (57%) after 64.8 Gy (p < 0.05).Conclusions: The data provide evidence for a significant effect of dose escalation on the response of human prostate cancer to irradiation and defines new standards for curative radiotherapy in this disease.     

First results of a phase I/II dose escalation trial in non-small cell lung cancer using three-dimensional conformal radiotherapy.

PURPOSE: To evaluate the feasibility of dose escalation in non-small cell lung cancer (NSCLC) using three-dimensional conformal radiation therapy. PATIENTS AND METHODS: The main eligibility criteria of the trial were: pathologically proven inoperable NSCLC, ECOG performance status or=grade 3 (SWOG), grade 3 early and grade 2 late esophageal toxicity or any other (RTOG) grade 3 or 4 complications). RESULTS: Fifty-five patients were included. Tumor stage was I/II in 47%, IIIA in 33% and IIIB in 20%. The majority of the patients received a dose of 74.3 Gy (n=17) or 81.0 Gy (n=23). Radiation pneumonitis occurred in seven patients: four patients developed a grade 2, two patients grade 3 and one patient a grade 4. Esophageal toxicity was mild. In 50 patients tumor response at 3 months follow-up was evaluable. In six patients a complete response was recorded, in 38 a partial response, five patients had stable disease and one patient experienced progressive disease. Only one patient developed an isolated failure in an uninvolved nodal area. So far the radiation dose was safely escalated to 87.8 Gy in group 1 (lowest rMLD), 81.0 Gy in groups 2 and 3 and 74.3 Gy in group 4. CONCLUSION: Three-dimensional conformal radiotherapy enables significant dose escalation in NSCLC. The maximum tolerable dose has not yet been reached in any risk group.     

Escalated dose for non-small-cell lung cancer with accelerated hypofractionated three-dimensional conformal radiation therapy.

BACKGROUND AND PURPOSE: To prospectively assess the feasibility and efficacy of a hypofractionated accelerated radiotherapy regimen (72 Gy in 24 daily fractions, 3 Gy per fraction) in patients (pts) with non-resectable non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS: We included 25 pts with a histologically or cytologically proven NSCLC, with KPS > or = 70 and < or =10% weight loss over prior three months, and with tumour stage I/II medically inoperable (9 pts) or non-resectable stage III a/b without pleural effusion (16 pts). Eleven pts received induction chemotherapy. No more than 30% of the combined lung volume could receive more than 25 Gy and the maximal biological effective dose to the spinal cord was maintained below 44 Gy. RESULTS: No grade-4 acute toxicity event was reported. Two pts had a treatment break because of grade-3 acute oesophagitis. Twenty-two pts were evaluable for long-term toxicity (median follow-up=9.7 months, range 4 to 30.2 months). There were 4 Grade-1 pulmonary and 2 Grade-1 oesophageal long-term toxicity events. Twenty-two pts were evaluable for tumour response with 7 complete and 8 partial responses, 5 stable diseases and 2 progressive diseases. The actuarial 1-year overall and thoracic-progression-free survival rates were 68% and 72% respectively. CONCLUSIONS: This study demonstrates the feasibility of the experimental radiotherapy schedule, however more data are needed to confirm its efficacy.     

Interplanner variability in carrying out three-dimensional conformal radiation therapy for non-small-cell lung cancer

This study evaluated the variability among six radiation therapy planners in planning radiation treatment for four patients with lung cancer using two treatment protocols. The interplanner variability for target conformity and homogeneity was smaller than the variability among the patients and planning approaches. The same was found for the dose volume indices achieved for most critical structures, indicating that interplanner variability is not likely to be an important source of variation in radiotherapy studies if concise treatment protocols are followed.     

非小细胞肺癌三维适形放射治疗临床Ⅰ和Ⅱ期剂量递增试验结果分析

目的：通过剂量递增试验试图获得非小细胞肺癌（NSCLC）病例三维适形放射的最大耐受剂量并观察其疗效。方法：50例Ⅱ－ⅢB期非小细胞肺癌病例先用前胸和后背后相对野常规分割放射治疗，剂量42Gy，21分次，4．2周完成，然后再用三维适形放射治疗进行肿瘤增加量，3Gy／次，1次／d,5d／周，剂量递增次数为9－12次，肿瘤总剂量递增水平为69、72、75和78Gy，以≥15％的患者出现美国肿瘤放射治疗协作组织（RTOG）3级或以上急性放射性肺损伤为限制剂量递标准。所有组病例给予以铂类药为基础的化疗，结果：50例NSCLC随访15－31个月，已完成剂量递增计划。近期疗效中完全缓解（CR）率为16％，部分缓解（PR）70％，无进展（NR）率为14％，总有效率（CR＋PR）为86％，1＋2级急性放射性食管炎发生率为56％，3例为10％，1＋2级急性放射性肺炎发生率为36％，3级为2％；1＋2级急性骨髓抑制发生率为58％，3级为8％，1＋2级放射性肺炎发生率为30％，全组中位生存时间2个月，1、2年生存率分别为70％、47％，1、2年局部控制率分别为80％、62％，结论：该剂量递增的方法和剂量能为大多数患者所耐受，在进一步随访晚期毒副作用后可获得最大耐受剂量，近期疗效令人鼓舞，远期疗效有效待进一步观察。     

Induction and concurrent chemotherapy with high-dose thoracic conformal radiation therapy in unresectable stage IIIA and IIIB non-small-cell lung cancer: a dose-escalation phase I trial.

PURPOSE: Local control rates at conventional radiotherapy doses (60 to 66 Gy) are poor in stage III non-small-cell lung cancer (NSCLC). Dose escalation using three-dimensional thoracic conformal radiation therapy (TCRT) is one strategy to improve local control and perhaps survival. PATIENTS AND METHODS: Stage III NSCLC patients with a good performance status (PS) were treated with induction chemotherapy (carboplatin area under the curve [AUC] 5, irinotecan 100 mg/m(2), and paclitaxel 175 mg/m(2) days 1 and 22) followed by concurrent chemotherapy (carboplatin AUC 2 and paclitaxel 45 mg/m(2) weekly for 7 to 8 weeks) beginning on day 43. Pre- and postchemotherapy computed tomography scans defined the initial clinical target volume (CTV(I)) and boost clinical target volume (CTV(B)), respectively. The CTV(I) received 40 to 50 Gy; the CTV(B) received escalating doses of TCRT from 78 Gy to 82, 86, and 90 Gy. The primary objective was to escalate the TCRT dose from 78 to 90 Gy or to the maximum-tolerated dose. RESULTS: Twenty-nine patients were enrolled (25 assessable patients; median age, 59 years; 62% male; 45% stage IIIA; 38% PS 0; and 38% > or = 5% weight loss). Induction CIP was well tolerated (with filgrastim support) and active (partial response rate, 46.2%; stable disease, 53.8%; and early progression, 0%). The TCRT dose was escalated from 78 to 90 Gy without dose-limiting toxicity. The primary acute toxicity was esophagitis (16%, all grade 3). Late toxicity consisted of grade 2 esophageal stricture (n = 3), bronchial stenosis (n = 2), and fatal hemoptysis (n = 2). The overall response rate was 60%, with a median survival time and 1-year survival probability of 24 months and 0.73 (95% CI, 0.55 to 0.89), respectively. CONCLUSION Escalation of the TCRT dose from 78 to 90 Gy in the context of induction and concurrent chemotherapy was accomplished safely in stage III NSCLC patients.     

非小细胞肺癌立体适形放疗的Ⅰ期临床剂量递增试验

目的 建立非小细胞肺癌适形放疗技术,试图获得患者适形放疗的最大耐受剂量（ＭＴＤ）,并观察其即期疗效。方法 １９９９年６月至２０００年６月,３８例Ⅱ～ⅢＢ期非小细胞肺癌患者进入本研究。常规放疗４２Ｇｙ后用适形放疗做肿瘤剂量递增。根据接受２０Ｇｙ照射的总肺体积面分比,计划的肿瘤剂量递增水平分别为６９、７２、７５、７８和８１Ｇｙ。大于ＲＴＯＧⅢ级放射性肺损伤为停止剂量递增的标准。结果 已完成放疗计划者有     

Prospective evaluation of early lung toxicity following three-dimensional conformal radiation therapy in non-small-cell lung cancer: preliminary results

PURPOSE: Radiation pneumonitis is the restricting complication following lung cancer irradiation. The correlation between dose-volume histograms (DVHs) and pneumonitis, with a clinical, radiological, and respiratory function evaluation was assessed. Special endpoint was the evaluation of respiratory function after three-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS: Fifty-four patients with non metastatic non-small-cell lung cancer (NSCLC) were treated with a curative intent with 3D-CRT (66 Gy). Thirty-one patients were treated postoperatively (pneumonectomy in 9 patients) for residual tumor or massive nodal involvement (N2 or N3); 23 patients were treated with exclusive radiotherapy. Clinical evaluation, CT scan, and pulmonary functional tests were performed before and 6 weeks after irradiation. The DVHs were calculated applying lung density heterogeneity. RESULTS: Twenty patients had radiation pneumonitis. Irradiation significantly decreased total lung capacity. Volume of the PTV2 (more than 200 cm(3)) was a significant prognostic factor for lung complication. CONCLUSION: DVHs combined with initial pulmonary functional tests can predict pulmonary toxicity and could allow us to adjust volume that received total highest dose with acceptable toxicity.     

Strategy for dose escalation using 3-dimensional conformal radiation therapy for lung cancer

PURPOSE: Local failure is a major obstacle to the cure of locally advancednon-small-cell lung cancer. 3-Dimensional conformal radiationtherapy (3-DCRT) selects optimal treatment parameters to increasedose to tumor and reduce normal tissue dose, potentially permittingdose escalation. There are several ongoing trials of dose escalationusing 3-dimensional conformal radiation therapy for non-small-celllung cancer. We performed this analysis to determine if dataderived from dose volume histograms could be used as the basisfor designing the method of dose escalation in these trials. METHODS AND MATERIALS: Between 1990 and 1993, 31 patients were treated with 3-DCRTand had complete normal tissue dose volume histograms createdas part of the planning process. The stage distribution wasstage I/TI 13%, stage IHa in 45%, and stage Illb in 42%. Themedian radiation dose to gross disease was 70.2 Gy (52.2–;72Gy). Elective mediastinal irradiation (50.4 Gy) was administeredto 52% (16/31) of patients. RESULTS: Thr toxicity encountered in this experience was pulmonary. Dose-volume-histogramdata were used to analyze the predictors of toxicity and showeda correlation between risk of pulmonary toxicity and indicesof dose to lung parenchyma. Grade 3 or higher pulmonary toxicityoccurredin 38% (3/8) of pts with > 30% of lung volume receiving >25 Gy, versus 4% (1/23) of pts. with < 30% lung receiving> 25 Gy (p =0.04). Grade 3 or higher pulmonary toxicity occurredin 29% (4/14) of patients with a predicted pulmonary normaltissue complication probability of 12% or higher versus 0% (0/17)in patients with a predicted probability of less than 12% (p=0.03).The single fatality occurred in a patient with a calculatedpneumonitis probability of 85% and a high percent (49%) lungvolume receiving > = 25 Gy. CONCLUSION: This preliminary experience demonstrates a correlation betweenlung dose-volume-histogram data and the risk of severe pulmonarytoxicity. This provides an opportunity to modify the methodof radiation dose escalan. Dose-volume-histogram data can allowescalation according to the risk to the lung parenchyma (whichis the major organ of concern) rather than escalation accordingto tumor dose levels. Because of the major inter-patient variabilityof intrathoracic tumor bulk and anatomic distribution, thisstrategy is intuitively appropriate. This approach may facilitatecompletion of dose escalation studies and identification ofmaximum tolerable pulmonary dose levels. lung cancer, radiation, 3-dimensional treatment planning     

Elective nodal irradiation in the treatment of non-small-cell lung cancer with three-dimensional conformal radiation therapy

PURPOSE: Dose escalation using three-dimensional conformal radiation therapy (3D-CRT) has been investigated as a means to improve local control. However, with higher doses, the risk of toxicity increases. Early in our experience, we ceased treating elective nodal areas (lymph node stations without evidence of tumor involvement) in an effort to decrease toxicity while treating the gross tumor to higher doses. This report measures the rate of regional failure without elective radiation therapy to uninvolved lymph nodes. METHODS AND MATERIALS: A total of 171 patients with non-small-cell lung cancer treated with 3D-CRT at Memorial Sloan-Kettering Cancer Center between 1991 and 1998 were reviewed. Only lymph node regions initially involved with tumor either by biopsy (55%) or radiographic criteria (node > or =15 mm in the short axis on CT) were included in the clinical target volume. Elective nodal failure was defined as a recurrence in an initially uninvolved lymph node in the absence of local failure. RESULTS: Only 11 patients (6.4%) with elective nodal failure were identified. With a median follow-up of 21 months in survivors, the 2-year actuarial rates of elective nodal control and primary tumor control were 91% and 38%, respectively. In patients who were locally controlled, the 2-year rate of elective nodal control was 85%. The median time to elective nodal failure was 4 months (range, 1-19 months). Most patients failed in multiple lymph node regions simultaneously. CONCLUSION: Local control remains one of the biggest challenges in the treatment of non-small-cell lung cancer. Most patients in our series developed local failure within 2 years of radiation therapy. The omission of elective nodal treatment did not cause a significant amount of failure in lymph node regions not included in the clinical target volume. Therefore, we will continue our policy of treating mediastinal lymph node regions only if they are clinically involved with tumor.     

A phase II trial of accelerated hypofractionated three-dimensional conformal radiation therapy in locally advanced non-small cell lung cancer

Purpose

The aim of this study is to evaluate the safety and efficacy of accelerated hypofractionated radiotherapy (HypoRT) combined with sequential chemotherapy in locally advanced non-small cell lung cancer (NSCLC).

Materials and methods

A total of 34 patients with stage III NSCLC were enrolled. All patients received accelerated HypoRT (initially 50 Gy/20 fractions, then a fraction dose of 3 Gy) using three-dimensional conformal radiation therapy (3D-CRT), omitting elective nodal irradiation (ENI), to a total dose of 65-68 Gy. All patients received two cycles of induction chemotherapy; 1-2 cycles of consolidation chemotherapy were given to 31 patients. The primary outcome measure was a profile of radiation toxicity. The secondary endpoints included overall survival (OS), progression-free survival (PFS), locoregional PFS (LR-PFS) and the pattern of initial failure.

Results

Radiation toxicity was minimal. The median and 3-year OS, PFS were 19.0 months, 32.1%; 10.0 months, 29.8%, respectively. The 1-, 2-, and 3-year LR-PFS were 69.6%, 60.9% and 60.9%, respectively. No patient experienced isolated elective nodal failure as the first site of failure.

Conclusion

This study suggests that accelerated HypoRT using 3D-CRT omitting ENI can be used in combination with sequential chemotherapy in locally advanced NSCLC.     

Dose escalation of docetaxel concomitant with hypofractionated, once weekly chest radiotherapy for non-small-cell lung cancer: a phase I study

Hypofractionated chest radiotherapy has been used as an alternative when standard fractionated schedules are neither practical nor feasible. To explore docetaxel as radiosensitizer in a hypofractionated chest irradiation schedule, a docetaxel dose escalation study was conducted in which 26 patients with advanced non-small-cell lung cancer (NSCLC) (stages III and IV) were enrolled. Docetaxel was administered 24 hours prior to irradiation (starting dose 10mg/m2; escalating in 5mg/m2 increments). Radiation was administered at 500 cGy (one fraction) once/wk for 10 consecutive weeks (5000 cGy total). The docetaxel dose was escalated up to 45 mg/m2/wk. The treatment was well tolerated over 10 consecutive weeks without requiring dose reductions or interruptions. Toxicities were mainly docetaxel related. One of 19 evaluable patients had a complete radiographic response within the radiation treatment port, 13 had a partial response, and 5 had stable disease. No patient recurred within the radiation field. Three patients who underwent surgical resection following treatment were pathologically down staged to stage I. This trial of a small group of patients supports, in selected patients, synchronous administration of effective hypofractionated, radiosensitized radiation therapy and optimized systemic chemotherapy.     

Induction chemotherapy plus three-dimensional conformal radiation therapy in the definitive treatment of locally advanced non-small-cell lung cancer

PURPOSE: To evaluate our institution's experience using chemotherapy in conjunction with three-dimensional conformal radiation therapy (3D-CRT). METHODS AND MATERIALS: From 1991 to 1998, 152 patients with Stage III non-small-cell lung cancer (NSCLC) were treated with 3D-CRT at Memorial Sloan-Kettering Cancer Center. A total of 137 patients (90%) were surgically staged with either thoracotomy or mediastinoscopy. The remainder were staged radiographically. Seventy patients were treated with radiation therapy alone, and 82 patients received induction chemotherapy before radiation. The majority of chemotherapy-treated patients received a platinum-containing regimen. Radiation was delivered with a 3D conformal technique using CT-based treatment planning. The median dose in the radiation alone group was 70.2 Gy, while in the combined modality group, it was 64.8 Gy. RESULTS: The median follow-up time was 30.5 months among survivors. Stage IIIB disease was present in 36 patients (51%) in the radiation-alone group and 57 patients (70%) in the combined-modality group. Thirty-nine patients had poor prognostic factors (KPS < 70 or weight loss > 5%), and they were equally distributed between the two groups. The median survival times for the radiation-alone and the combined-modality groups were 11.7 months and 18.1 months, respectively (p = 0.001). The 2-year rates of local control in the radiation-alone and combined-modality groups were 35.4% and 43.1%, respectively (p = 0.1). Grade 3 or worse nonhematologic toxicity occurred in 20% of the patients receiving radiation alone and in 16% of those receiving chemotherapy and radiation. Overall, there were only 4 cases of Grade 3 or worse esophagitis. CONCLUSION: Despite more Stage IIIB patients in the combined-modality group, the addition of chemotherapy to 3D-CRT produced a survival advantage over 3D-CRT alone in Stage III NSCLC without a concomitant increase in toxicity. Chemotherapy thus appears to be beneficial, even in patients who are receiving higher doses of radiation therapy than are typically given with conventional techniques. Because locoregional failure remains a major challenge in patients with advanced disease, 3D-CRT in conjunction with chemotherapy may allow safe treatment to the dose levels required to further enhance local control.     

Ⅲ+Ⅳ期非小细胞肺癌三维适形或调强放疗中复合指标预测放射性肺炎前瞻性临床研究

目的 探讨非小细胞肺癌三维适形或调强放疗正常肺V5和V10联合V20评价放射性肺炎(RP)的意义.方法 采用三维适形或调强后程加速超分割放疗经病理或细胞学证实初治非小细胞肺癌患者90例,其中Ⅲa期6例、Ⅲb期29例、Ⅳ期55例.放疗剂量61～80 Gy,中位数70 Gy.由剂量体积直方图计算全肺V5、V10、V20、V30、平均肺剂量(MLD),对侧肺V5、V10及同侧肺V30.用CTC3.0标准评估肺损伤.结果 90例患者中发生RP为1级29例、2级23例、3级5例、4级1例、5级1例.全肺V5、V10、V20、对侧肺V10、大体肿瘤体积(GTV)、计划靶体积、射野数目与≥1级RP相关(χ2=2.04、2.05、2.01、4.62、6.50、5.61、5.61,P=0.044、0.043、0.047、0.030、0.010、0.020、0.020),全肺V5、V10、V20和V30、MLD与≥2级RP相关(χ2=2.05、2.20、2.96、4.96、5.20,P=0.040、0.030、0.000、0.030、0.020).多因素分析显示GTV与≥1级RP发生相关(χ2=4.06,P=0.044),V20与≥2级RP发生相关(χ2=9.61,P=0.002).全肺V5、V10、V20的中位数分别为66%、48%、31%.V20>31%时≥2级RP概率增加,V20>31%+V10>48%+V5>66%时≥2级RP概率增加,V20>31%+V5>66%时≥2级RP概率增加;V20>31%时V10>48%与<48%比较RP概率相似,V20≤31%时V5>66%与<66%、V10>48%与<48%比较RP概率也相似.性别、年龄、临床分期、病理类型、治疗方式、KPS与≥1、2级RP无关.结论 肺V5、V10联合V20评价放射性肺炎的发生可能提高预测放射性肺炎的能力.     

Dose-volume factors contributing to the incidence of radiation pneumonitis in non-small-cell lung cancer patients treated with three-dimensional conformal radiation therapy

PURPOSE: To analyze acute lung toxicity data of non-small-cell lung cancer patients treated with three-dimensional conformal radiation therapy in terms of dosimetric variables, location of dose within subvolumes of the lungs, and models of normal-tissue complication probability (NTCP). METHODS AND MATERIALS: Dose distributions of 49 non-small-cell lung cancer patients treated in a dose escalation protocol between 1992 and 1999 were analyzed (dose range: 57.6-81 Gy). Nine patients had RTOG Grade 3 or higher acute lung toxicity. Correlation with dosimetric and physical variables, as well as Lyman and parallel NTCP models, was assessed. Lungs were evaluated as a single structure, as superior and inferior halves (to assess significance of dose to upper and lower lungs), and as ipsilateral and contralateral lungs. RESULTS: For the whole lung, Grade 3 or higher pneumonitis was significantly correlated (p 0.5 for superior lung indices, and >0.1 for contralateral lung indices studied). CONCLUSIONS: For these patients, commonly used dosimetric and NTCP models are significantly correlated with >or= Grade 3 pneumonitis. Equivalently strong correlations are found in the lower portion of the lungs and the ipsilateral lung, but not in the upper portion or contralateral lung.     

Ⅲ期非小细胞肺癌累及野照射的可行性研究

目的探讨Ⅲ期非小细胞肺癌（NSCLC）累及野照射的可行性。方法200例接受三维适形放疗的Ⅲ期NSCLC患者,随机分为2组。累及野照射组（IFI组）仅照射原发灶和短径〉10mm的淋巴结,照射剂量为68～74Gy／7～9w;选择性淋巴结照射组（ENI组）照射野包括原发灶、同侧肺门、隆突下及隆突以上纵隔淋巴引流区,当上纵隔有淋巴结转移时,包括锁骨上淋巴引流区,照射剂量为60～64Gy／6～7．5w。结果IFI组和ENI组的总有效率分别为90．0％和79．0％;放射性肺炎发生率分别为17．0％和29．0％（P=0．04）。1年内原发灶复发率IFI组（13．0％）明显低于ENI组（23．0％）;1年内累及野照射区内淋巴结复发率IFI组为10．0％,ENI组为20．0％（P=0．048）,预防性照射区内淋巴结复发率IFI组为21．0％,ENI组为16．0％（P=0．39）;1、2、3年总生存率,IFI组分别为67．2％、38．7％和27．3％,ENI组分别为59．7％、25．6％和19．2％,其中2年总生存率两组间差异有统计学意义（P=0．048）。结论Ⅲ期NSCLC采用累及野照射,患者耐受性好,预防照射区内淋巴结复发率无增加．通讨照射剂量的提高．有草延长患者的生存期。