非小细胞肺癌低分割放疗后放射性肺炎的影响因素分析

目的 探讨非小细胞肺癌低分割放疗后放射性肺炎的影响因素.方法 收集120例接受低分割放疗的非小细胞肺癌患者的临床资料,对术后3个月内发生放射性肺炎的危险因素进行Logistic回归分析.结果120例患者中,37例(30.83%)患者发生放射性肺炎,83例(69.17%)患者未发生放射性肺炎.有肺部疾病史、肿瘤体积≥40 cm3、V20≥12%、患肺最大受照剂量≥54 Gy、有化疗史是影响非小细胞肺癌低分割放疗后放射性肺炎的独立危险因素(P﹤0.05).结论 非小细胞肺癌低分割放疗后放射性肺炎的发生是各项指标相互作用的结果,在制定放疗计划时需综合考虑各项指标,及时调整治疗方案以降低放射性肺炎的发生率.     

Central thoracic lesions treated with hypofractionated stereotactic body radiotherapy

Purpose

To investigate the toxicity and outcome after moderately hypofractionated stereotactic body radiotherapy (SBRT) for central thoracic lesions.

Methods

Fifty-three patients undergoing 63 courses of SBRT for central thoracic lesions were retrospectively reviewed. Ninety-eight lesions received 30-63 Gy in 2.5-5.0 Gy fractions using the Novalis ExacTrac^® patient positioning platform.

Results

The 2-year lesion local control was 73%. Larger lesion volume was associated with poorer local control. The 2-year overall survival of patients with Stage I NSCLC, Stages II-III NSCLC and limited metastatic disease was 72%, 12% and 49%, respectively. There were four patient deaths from pulmonary causes, potentially grade 5 toxicities, though three had comorbid pulmonary conditions which may have contributed to the cause of death. One patient died from hemoptysis after undergoing two courses of SBRT to a mediastinal lesion. Most other deaths were attributable to metastatic progression.

Conclusions

Moderately hypofractionated SBRT to central thoracic lesions is effective with respect to local control and toxicity. Further dose escalation can provide an opportunity for better tumor control. Even with less aggressive dose fractionation, pulmonary deaths can occur, though it is difficult to ascertain the extent to which SBRT contributed to the death of patients with comorbid pulmonary conditions.     

Predictive parameters of symptomatic radiation pneumonitis following stereotactic or hypofractionated radiotherapy delivered using volumetric modulated arcs

Purpose

To identify dosimetric factors that predict development of radiation pneumonitis (RP) following stereotactic or hypofractionated radiotherapy for lung tumors.

Methods

Seventy-nine consecutive patients with either a planning target volume (PTV) > 100 cm³ (n = 69) or prior pneumonectomy or bi-lobectomy (n = 13) were identified. Radiation doses (range: 5–50 Gy, with 5 Gy increments) were converted to equivalent doses (EQD_2 Gy) (α/β = 3). Total lung (TL), ipsilateral (IL) and contralateral lung (CL) volumes minus PTV, receiving 5 Gy (V5) up to 50 Gy (V50) and mean lung dose (MLD) were analyzed. Predictors of grade ?3 RP (CTCAEv4.03) were identified with concordance-statistics (C-statistic) and p-values used to quantify the performance of the model. Factors found to be significant were entered into a recursive partitioning analysis (RPA).

Results

Median PTV was 150 cm³. Grade ?3 RP was observed in 8 patients (10%). In univariable analysis, CL-MLD, CL-V5-15, TL-MLD, TL-V5-V10 and ITV size were predictive of RP (p < 0.05). In multivariable analysis, contralateral MLD (p = .007) and ITV (p = .063) were the strongest predictors of grade ?3 RP, with excellent discrimination (C-statistic: 0.868).

Conclusion

Contralateral MLD and ITV size are both strong predictors of grade ?3 RP post treatment. Planning constraints should aim to keep contralateral MLD below 3.6 Gy.     

Utilization of hypofractionated radiation therapy in older glioblastoma patients

Background

Though the optimal treatment regimen in older patients with glioblastoma multiforme (GBM) remains to be established, multiple randomized studies have supported the use of hypofractionated (1–3?weeks) versus traditional regimens (6?weeks). Here we examine hypofractionated regimen practice patterns among older patients with GBM.

Radiation pneumonitis in patients treated for breast cancer

An analysis of 201 breast cancer patients having post-operative radiotherapy to the chest wall between January 1981 and May 1983 has identified those patients with chest symptoms following radiotherapy and these have been critically assessed with regard to the possibility of radiation pneumonitis being their cause. The inner contour of the anterior chest wall has been reconstructed on the radiation plan and the area of lung irradiated to a significant level in the mid-plane of the tangential fields determined. The incidence and severity of pneumonitis has been shown to rise exponentially with increase in the irradiated volume. A method of measuring the thickness of the chest wall using the simulator has been devised so that this information may be incorporated into the planning process in order to reduce the area of lung at risk.     

Oligometastatic breast cancer treated with curative-intent stereotactic body radiation therapy

Purpose Prospective pilot study to assess patient outcome after stereotactic body radiation therapy (SBRT) for limited metastases from breast cancer. Methods Forty patients with ≤5 metastatic lesions received curative-intent SBRT, while 11 patients with >5 lesions, undergoing SBRT to ≤5 metastatic lesions, were treated with palliative-intent. Results Among those treated with curative-intent, 4-year actuarial outcomes were: overall survival of 59%, progression-free survival of 38% and lesion local control of 89%. On univariate analyses, 1 metastatic lesion (versus 2–5), smaller tumor volume, bone-only disease, and stable or regressing lesions prior to SBRT were associated with more favorable outcome. Patients treated with palliative-intent SBRT were spared morbidity and mortality from progression of treated lesions, though all developed further metastatic progression shortly (median 4 months) after enrollment. Conclusions SBRT may yield prolonged survival and perhaps cure in select patients with limited metastases. Palliative-intent SBRT may be warranted for symptomatic or potentially symptomatic metastases.     

Radiation pneumonitis: correlation of toxicity with pulmonary metabolic radiation response

PURPOSE: To characterize the relationship between radiation pneumonitis (RP) clinical symptoms and pulmonary metabolic activity on post-treatment [(18)F]-fluorodeoxyglucose positron emission tomography (FDG-PET). PATIENTS AND METHODS: We retrospectively studied 101 esophageal cancer patients who underwent restaging FDG-PET/computed tomography imaging 3-12 weeks after completing thoracic radiotherapy. The National Institutes of Health Common Toxicity Criteria, version 3, was used to score the RP clinical symptoms. Linear regression was applied to the FDG-PET/computed tomography images to determine the normalized FDG uptake vs. radiation dose. The pulmonary metabolic radiation response (PMRR) was quantified as this slope. Modeling was performed to determine the interaction of PMRR, mean lung dose (MLD), and the percentage of lung receiving >20 Gy with RP outcomes. RESULTS: Of the 101 patients, 25 had Grade 0, 10 had Grade 1, 60 had Grade 2, 5 had Grade 3, and 1 had Grade 5 RP symptoms. Logistic regression analysis demonstrated that increased values of both MLD and PMRR were associated with a greater probability of RP clinical symptoms (p = 0.032 and p = 0.033, respectively). Spearman's rank correlation found no association between the PMRR and the dosimetric parameters (planning target volume, MLD, percentage of lung receiving >5-30 Gy). Twofold cross-validation demonstrated that the combination of MLD and PMRR was superior to either alone for assessing the development of clinical RP symptoms. The combined MLD (or percentage of lung receiving >20 Gy) and PMRR had a greater sensitivity and accuracy (53.3% and 62.5%, respectively) than either alone. CONCLUSION: The results of this study have demonstrated a significant correlation between RP clinical symptoms and the PMRR measured by FDG-PET/computed tomography after thoracic radiotherapy.     

Combined hypofractionated radiation and hormone therapy for the treatment of intermediate-risk prostate cancer

PURPOSE: Because of the low alpha/beta value of prostate cancer, a therapeutic gain may be possible with a hypofractionated radiation scheme, and this gain may be further increased with the adjunct of hormone therapy. A Phase II study was undertaken to study the toxicity of such a treatment. METHODS AND MATERIALS: Forty-two patients with intermediate-risk prostate cancer were recruited for this study. Neoadjuvant and concomitant hormone therapy consisted of one injection of leuprolide acetate (4-month preparation) and 1 month of oral nonsteroidal, anti-androgen medication starting on the day of the injection. Radiation treatment was started 8 weeks after the injection and patients received 57 Gy in 19 fractions. RESULTS: Median follow-up was 46 months. The treatment was well tolerated and no interruptions occurred. The majority (59%) had Grade 0 or 1 acute genitourinary (GU) toxicity, whereas 36% had Grade 2 and 5% had Grade 3 acute GU toxicity. Only Grade 1 or 2 gastrointestinal toxicity was seen. All chronic toxicity was of Grade 1 or 2 except for 3 patients (8%) with Grade 3 toxicity. Sixty-eight percent (68%) of patients had no long-term side effects from the treatment. At time of analysis, 79% showed no sign of treatment failure. CONCLUSIONS: Hypofractionated radiation with neoadjuvant and concomitant hormone therapy is well tolerated with no significant short- or long-term morbidity. Control for this risk group is good, and comparative Phase III studies should be undertaken to determine whether this treatment is superior to new evolving treatments.     

CT appearance of radiation injury of the lung and clinical symptoms after stereotactic body radiation therapy (SBRT) for lung cancers: Are patients with pulmonary emphysema also candidates for SBRT for lung cancers?

PURPOSE: The purpose of this study was to analyze the computed tomographic (CT) appearance of radiation injury to the lung and clinical symptoms after stereotactic body radiation therapy (SBRT) and evaluate the difference by the presence of pulmonary emphysema (PE) for small lung cancers. METHODS AND MATERIALS: In this analysis, 45 patients with 52 primary or metastatic lung cancers were enrolled. We evaluated the CT appearance of acute radiation pneumonitis (within 6 months) and radiation fibrosis (after 6 months) after SBRT. Clinical symptoms were evaluated by Common Terminology Criteria for Adverse Events, version 3.0. We also evaluated the relationship between CT appearance, clinical symptoms, and PE. RESULTS: CT appearance of acute radiation pneumonitis was classified as follows: (1) diffuse consolidation, 38.5%; (2) patchy consolidation and ground-glass opacities (GGO), 15.4%; (3) diffuse GGO, 11.5%; (4) patchy GGO, 2.0%; (5) no evidence of increasing density, 32.6%. CT appearance of radiation fibrosis was classified as follows: (1) modified conventional pattern, 61.5%; (2) mass-like pattern, 17.3%; (3) scar-like pattern, 21.2%. Patients who were diagnosed with more than Grade 2 pneumonitis showed significantly less no evidence of increased density pattern and scar-like pattern than any other pattern (p=0.0314, 0.0297, respectively). Significantly, most of these patients with no evidence of increased density pattern and scar-like pattern had PE (p=0.00038, 0.00044, respectively). CONCLUSION: Computed tomographic appearance after SBRT was classified into five patterns of acute radiation pneumonitis and three patterns of radiation fibrosis. Our results suggest that SBRT can be also safely performed even in patients with PE.     

A case of metachronous bilateral Breast Cancer with bilateral radiation pneumonitis after breast-conserving therapy

We report a patient with metachronous bilateral breast cancer who has twice developed radiation pneumonitis after breast-conserving therapy for each breast. The patient was a 48-year-old woman, who presented with Stage I right breast cancer. After wide excision of the right breast tumor and dissection of level I axillary lymph nodes, systemic therapy with oral 5-FU and tamoxifen was started. Subsequently, tangential irradiation with a total dose of 50 Gy in 25 fractions was given. Seven months after irradiation, she developed respiratory symptoms and radiation pneumonitis was diagnosed. The symptoms resolved with oral prednisolone. Thirty months after the right breast cancer treatment, Stage I left breast cancer was diagnosed. After wide excision of the left breast tumor and partial removal of the level I axillary lymph nodes, the same oral systemic chemo-hormonal therapy was initiated. Thereafter, tangential irradiation with a total dose of 50 Gy in 25 fractions was given. Four months after irradiation, she developed respiratory symptoms. A chest X-ray showed an area of increased density in the left lung consistent with radiation pneumonitis. The symptoms were mild and they improved spontaneously without medication. Although there is insufficient evidence to justify or withhold whole breast radiation therapy from patients with a history of contralateral breast cancer and radiation pneumonitis, it is essential to discuss the adequacy of whole breast irradiation and the possibility of alternative approaches, such as breast-conserving surgery without irradiation or partial breast irradiation for this rare condition.     

Evaluation of serum KL-6 as a predictive marker of radiation pneumonitis in patients with breast-conservation therapy

Background Although radiation pneumonitis in radiotherapy following breast-conservation surgery is rare, it may lead to severe pneumonitis as well as to other types of pulmonary dysfunction. This study examined the usefulness of the serum KL-6 level as a new marker for the early detection of radiation pneumonitis.Methods Twenty-nine consenting patients served as subjects (age range, 32–78 years; mean age, 51 years) between 2001 and 2002. A total tangential irradiation dose of 50Gy/25 fractions (fr) was administered for 5 weeks, using a 4-MV X-ray, and an additional 10Gy/5fr for 1 week of 6-MeV electron-beam irradiation was performed for patients with pathological tumor cell findings in the excised tumor margins. Levels of serum KL-6 were measured before and after radiotherapy.Results Four patients developed radiation pneumonitis, all of whom had elevated post-therapy KL-6 levels. Patients with lower or unchanged KL-6 levels did not develop radiation pneumonitis. There was a significant difference in serum KL-6 levels between patients with and without radiation pneumonitis (P = 0.0421). KL-6 levels remained below the threshold value of 465U/ml in all patients.Conclusion For the early detection of radiation pneumonitis following breast-conservation surgery, and to assess the efficacy of therapy, the monitoring and measuring of changes in KL-6 levels before and after radiotherapy is more important than comparing KL-6 levels against the threshold value. Measuring KL-6 serum levels is also useful in assessing the efficacy of therapy for radiation pneumonitis.     

Stereotactic body radiotherapy for lung tumors in patients with subclinical interstitial lung disease: The potential risk of extensive radiation pneumonitis

Purpose

To evaluate the toxicity and efficacy of thoracic stereotactic body radiotherapy (SBRT) in patients with subclinical interstitial lung disease (ILD).

Methods and materials

One hundred patients with 124 lung tumors were treated with SBRT at our institution according to our own protocols; patients with subclinical (untreated and oxygen-free) ILD were treated with SBRT, while those with clinical ILD (post- or under treatment) were not. The administration of 48 Gy in four fractions was used in 103 (83%) of the 124 tumors. The presence of subclinical ILD in the pre-SBRT CT findings was reviewed by two chest radiologists. The relationships between radiation pneumonitis (RP) and clinical factors were investigated.

Results

Subclinical ILD was recognized in 16 (16%) of 100 patients. Grade 2–5 RP was recognized in 13 (13%) of 100 patients. Grade 2–5 RP was observed in three (19%) of 16 patients with subclinical ILD. Subclinical ILD was not found to be a significant factor influencing Grade 2–5 RP; however, extensive RP beyond the irradiated field, including the contralateral lung, was recognized in only three patients with subclinical ILD, and the rate of extensive RP was significantly high in the patients with subclinical ILD. Grade 4 or 5 extensive RP was recognized in only two patients with subclinical ILD. Dosimetric factors of the lungs (V5, V10, V15, V20, V25, MLD) were significantly associated with Grade 2–5 RP. The three-year overall survival and local control rates of all patients were 53% and 86%, respectively. No significant differences were seen in either overall survival or local control rates between the patients with ILD and those without ILD.

Conclusions

Subclinical ILD was not found to be a significant factor for Grade 2–5 RP or clinical outcomes in the current study; however, uncommon extensive RP can occur in patients with subclinical ILD.     

肺癌与食管癌螺旋断层放疗致放射性肺炎的临床观察

目的 探讨螺旋断层放疗（HT）治疗肺癌与食管癌致放射性肺炎的发生情况及与双肺剂量体积（DVH）和临床病理特征的关系。方法 回顾性分析HT 治疗的19例肺癌和14食管癌患者的临床资料。全组患者中13例仅行HT治疗,20例联合化疗。放疗剂量：小细胞肺癌54～61.8Gy／27～28次,非小细胞肺癌54～66Gy／25～31次,食管癌60～66Gy／28～30次。结果 全组33例患者中,发生0级放射性肺炎8例（24.2％）,1级15例（45.4％）,2级1例（3.0％）,3级5例（15.2％）,5级4例（12.1％）。DVH参数分析显示,发生≥2级放射性肺炎与V30～V45有关,与V5～V25、双肺平均剂量（MLD）、计划靶区（PTV）无关。临床病理特征中,发生≥2级放射性肺炎与ECOG评分有关,与病种、性别、年龄、吸烟、慢性阻塞性肺病和化疗情况无关。结论 HT治疗肺癌与食管癌未明显增加放射性肺炎的发生率,一般状态差、分期晚的患者应严格限制DVH。     

Early pulmonary toxicity following lung stereotactic body radiation therapy delivered in consecutive daily fractions

Background and purpose

Identify the incidence of early pulmonary toxicity in a cohort of patients treated with lung stereotactic body radiation therapy (SBRT) on consecutive treatment days.

Material and methods

A total of 88 lesions in 84 patients were treated with SBRT in consecutive daily fractions (Fx) for medically inoperable non-small cell lung cancer or metastasis. The incidence of pneumonitis was evaluated and graded according to the NCI CTCAE v3.0.

Results

With a median follow-up of 15.8 months (range 2.5-28.6), the median age at SBRT was 71.8 years (range 23.8-87.8). 47 lesions were centrally located and 41 were peripheral. Most central lesions were treated with 48 Gy in 4 Fx, and most peripheral lesions with 54 Gy in 3 Fx. The incidence of grade ?2 pneumonitis was 12.5% in all patients treated, and 14.3% among the subset of patients treated with 54 Gy in 3 Fx. A total of two grade 3 toxicities were seen as one grade 5 toxicity in a patient treated for recurrence after pneumonectomy.

Conclusions

Treating both central and peripheral lung lesions with SBRT in consecutive daily fractions in this cohort was well tolerated and did not cause excessive early pulmonary toxicity.     

立体定向放疗联合免疫治疗晚期恶性肿瘤进展

晚期肺转移癌或黑素瘤中放疗联合免疫检测点抑制剂,封闭免疫抑制通路,增强抗肿瘤免疫应答,在临床上明显改善生存。体部立体定向放疗大剂量精准照射到肿瘤靶区,最大程度避免周围正常组织损伤,同时还诱导相关细胞因子和免疫分子表达,较常规放疗更能诱导强烈的免疫反应及远隔效应,更适合与免疫联合。已有研究表明总剂量和分割模式是调节放疗免疫反应的重要参数;放疗与免疫序贯时机显著影响疗效,肿瘤浸润淋巴细胞、PD-L1表达水平和MMR缺陷可能是预测放疗免疫治疗的重要指标。采用合理的放疗剂量和分割模式,选择最佳序贯时机和有效的预测标记物,SBRT联合免疫可以最大程度激活全身免疫反应,发挥远隔效应协同作用晚期恶性肿瘤。