GOECP/SEOR radiotheraphy guidelines for non-small-cell lung cancer

Non-small cell lung cancer (NSCLC) is a heterogeneous disease accounting for approximately 85% of all lung cancers. Only 17% of patients are diagnosed at an early stage. Treatment is multidisciplinary and radiotherapy plays a key role in all stages of the disease. More than 50% of patients with NSCLC are treated with radiotherapy (curative-intent or palliative). Technological advances-including highly conformal radiotherapy techniques, new immobilization and respiratory control systems, and precision image verification systems-allow clinicians to individualize treatment to maximize tumor control while minimizing treatment-related toxicity. Novel therapeutic regimens such as moderate hypofractionation and advanced techniques such as stereotactic body radiotherapy (SBRT) have reduced the number of radiotherapy sessions. The integration of SBRT into routine clinical practice has radically altered treatment of early-stage disease. SBRT also plays an increasingly important role in oligometastatic disease. The aim of the present guidelines is to review the role of radiotherapy in the treatment of localized, locally-advanced, and metastatic NSCLC. We review the main radiotherapy techniques and clarify the role of radiotherapy in routine clinical practice. These guidelines are based on the best available evidence. The level and grade of evidence supporting each recommendation is provided.     

GOECP/SEOR radiotherapy guidelines for thymic epithelial tumours

Thymic epithelial tumours (TET) are rare, heterogeneous neoplasms that range from resectable indolent tumours to aggressive thymic carcinomas with a strong tendency to metastasize. The pathological diagnosis is complex, in part due to the existence of several different classification systems. The evidence base for the management of TETs is scant and mainly based on non-randomised studies and retrospective series. Consequently, the clinical management of TETs tends to be highly heterogenous, which makes it difficult to improve the evidence level. The role of technological advances in the field of radiotherapy and new systemic therapies in the treatment of TETs has received little attention to date. In the present clinical guidelines, developed by the GOECP/SEOR, we review recent developments in the diagnosis and classification of TETs. We also present a consensus-based therapeutic strategy for each disease stage that takes into consideration the best available evidence. These guidelines focus primarily on the role of radiotherapy, including recent advances, in the management of TETs. The main aim of this document is to promote the standardisation of clinical practice and lay the foundations for future studies to clarify the main unresolved questions related to the optimal management of TET.     

GOECP/SEOR clinical guidelines on radiotherapy for malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a rare tumor with poor prognosis and rising incidence. Palliative care is common in MPM as radical treatment with curative intent is often not possible due to metastasis or extensive locoregional involvement. Numerous therapeutic advances have been made in recent years, including the use of less aggressive surgical techniques associated with lower morbidity and mortality (e.g., pleurectomy/decortication), technological advancements in the field of radiotherapy (intensity-modulated radiotherapy, image-guided radiotherapy, stereotactic body radiotherapy, proton therapy), and developments in systemic therapies (chemotherapy and immunotherapy). These improvements have had as yet only a modest effect on local control and survival. Advances in the management of MPM and standardization of care are hampered by the evidence to date, limited by high heterogeneity among studies and small sample sizes. In this clinical guideline prepared by the oncological group for the study of lung cancer of the Spanish Society of Radiation Oncology, we review clinical, histologic, and therapeutic aspects of MPM, with a particular focus on all aspects relating to radiotherapy, including the current evidence base, associations with chemotherapy and surgery, treatment volumes and planning, technological advances, and reradiation.     

海马区保护治疗小细胞肺癌全脑照射的研究进展

小细胞肺癌(SCLC)患者中约15%~20%初诊时已有脑转移,超过80%的患者最终会发展成为脑转移。全脑放疗(WBRT)是肺癌脑转移的标准治疗。全脑预防性照射(PCI)是预防SCLC脑转移的有效治疗手段。随着治疗技术的提高和治疗手段的规范,SCLC患者生存期的延长,采用螺旋断层放疗(TOMO)技术海马保护的WBRT用于PCI或脑转移患者,能够降低神经认知功能损伤,提高患者生活质量。     

VPC方案化疗联合脑部放疗治疗小细胞肺癌脑转移

背景与目的　放射治疗是治疗脑转移的主要手段,而到目前为止化疗与放疗联合治疗脑转移的研究较少。本研究旨在评价VPC(鬼臼噻吩甙+顺铂+司莫司汀)方案化疗联合脑部放疗治疗小细胞肺癌(small cell lung cancer, SCLC)脑转移患者的近期疗效及不良反应。方法　60例SCLC脑转移患者接受VPC方案化疗。脑部放疗于化疗第一周期的第6天开始,全脑照射剂量为30 Gy。残留病灶≤3个时,行缩野追加剂量20 Gy;残留病灶>3个时,继续全脑追加剂量10 Gy。化疗至少2周期及脑部放疗结束后,行脑部和胸部CT或MRI评价疗效。结果　全组60例患者均按计划完成脑部放疗与化疗,其中52例对残留病灶完成缩野治疗。治疗后全组肺部原发灶的有效率为46.7%(28/60);脑部病灶总有效率为60.0%(36/60)。48 例治疗前有神经系统症状和体征的患者均有不同程度的改善。不良反应有骨髓抑制、胃肠道反应、便秘和脱发。随诊率93.3%,中位生存期11.3个月,1年生存率为43.3%,2年生存率为35.0%,5 年生存率为6.7%。结论　化疗联合脑部放疗治疗SCLC脑转移,毒性反应轻,患者能够接受,近期疗效较理想。     

GOECP/SEOR clinical recommendations for lung cancer radiotherapy during the COVID-19 pandemic

The coronavirus disease 2019 crisis has had a major and highly complex impact on the clinical practice of radiation oncology worldwide. Spain is one of the countries hardest hit by the virus, with devastating consequences. There is an urgent need to share experiences and offer guidance on decision-making with regard to the indications and standards for radiation therapy in the treatment of lung cancer. In the present article, the Oncological Group for the Study of Lung Cancer of the Spanish Society of Radiation Oncology reviews the literature and establishes a series of consensus-based recommendations for the treatment of patients with lung cancer in different clinical scenarios during the present pandemic.     

小细胞肺癌的三维适形放射治疗

目的 分析三维适形放射治疗（3DCRT）在小细胞肺癌（SCLC）治疗中的可行性、效果和放射损伤情况。方法 19例SCLC患者中,局限期18例,广泛期1例。18例采用放化疗综合治疗,1例采用单独放疗。放疗单次剂量2Gy,每周5次,中位总剂量54Gy。化疗多采用卡铂或顺铂＋VP-16为主的方案,4～6个周期。中位随访24个月。结果 （1）全组患者CR率为31．6％（6／19）,PR率为47．4％（9／19）,SD率为21．1％（4／19）,有效率为79．0％。1年总生存率（OS）为71、7％,2年OS为35．8％,中位生存时间为19个月。1,2年无局部进展生存率均为94．7％。（2）2级急性放射性肺损伤为5．3％（1／19）,2级晚期放射性肺损伤为5．3％（1／19）,2级急性放射性食管损伤10．5％（2／19）,2级血液学毒性为10．5％（2／19）。结论 3DCRT用于SCLC治疗是可行的,患者能够获得较好的近期疗效和2年生存率,SCLC的三维适形放射治疗值得进一步研究。     

Is there a place for low-dose chest and prophylactic brain irradiation in limited-disease small cell lung cancer

The aim of the study is to evaluate the outcome of low-dose bifractionated up-front radiotherapy (RT) followed by chemotherapy (CHT) in limited-disease small cell lung cancer (LD-SCLC). From December 1999 to February 2002, 20 LD-SCLC consecutive patients were treated by initial involved-field thoracic irradiation of 2 Gy twice daily to a total dose of 20 Gy, and concomitant prophylactic cranial irradiation (PCI) of 1.8 Gy twice daily to a total dose of 18 Gy followed 3 days later by 4–6 cycles of CHT with cisplatin and etoposide. Median follow-up was 66 months (52–77). There were no Grade 3–4 esophagitis or pneumonitis. Response rate was 90%, 45% of the patients showing a complete and 45% a partial response. Median time to first event was 13 months. Forty percent showed local infield recurrence, while 55% presented distant metastasis, 4 of them in the brain. Median survival time was 28 months. The Kaplan–Meier 1-, 3-, and 5-years survival rates were 95%, 35%, and 21%, respectively. Salvage RT was applied for local recurrence in 7 patients and for distant metastasis in 7 patients. The rate of brain recurrence with up-front low-dose PCI is favorable and should be further evaluated. Although the response and survival rates are promising, the high number of local recurrences indicates that the irradiation dose is insufficient for patients whose disease can be encompassed within a radical radiation portal.     

Follow-up neurological evaluation in patients with small cell lung carcinoma treated with prophylactic cranial irradiation and chemotherapy

The safety of prophylactic cranial irradiation (PCI) has recently been questioned, based on reports of computerized tomographic abnormalities mainly seen in children, who received PCI and chemotherapy, primarily for acute lympbocytic leukemia. In order to clarify the significance of these findings, we examined a series of adult patients who were long term survivors (18–48 months, median 26 months, after all treatment). These patients were treated with combination radiotherapy and chemotherapy for small cell lung carcinoma and received cranial irradiation in the absence of known brain involvement by tumor. Patients were divided into three groups: three patients who received PCI + intrathecal metbotrexate (MTX) (Group 1), and ten who received only PCI (Group 2). An additional three patients (Group 3) were identified as long term survivors (41–70 months after all treatments) of a similar treatment program without any central nervous system (CNS) prophylaxis. All patients received an extensive evaluation of a variety of clinical parameters, EEG, and computer tomography (CT). Although CT abnormalities were detectable (mild cerebral atrophy in eight patients, encephaiomalacia in one of the 13 patients with CNS prophylaxis, and wild atrophy in two of the three patients without CNS prophylaxis~ so significant clinical abnormalities or EEG changes were detectable. While this group of patients is small, it is a unique cohort: adults who have received cranial irradiation in the absence of known brain tumor with long term follow-up. The precise role of CNS prophylaxis in the etiology of CT abnormalities is unclear, and the lack of clinically significant changes would suggest no contraindication to PCI when indicated.     

111例非小细胞肺癌脑转移的治疗与预后

背景与目的 肺癌脑转移临床表现各异，尚无标准治疗方案。本研究的目的是回顾性分析非小细胞肺癌（NSCLC）脑转移的个体化治疗策略以及全身化疗与全脑放疗的时序对生存期的影响。方法 纳入111例1995年9月至2004年5月伴脑转移的NSCLC患者，根据确诊时有无中枢神经系统（CNS）症状归纳为有症状组（37例）和无症状组（74例）：前者首选全脑放疗（WBRT）继之全身化疗；后者以全身化疗为主，择期行WBRT。化疗主要为含铂方案。WBRT：DT30～40Gy／20次。治疗过程中49例曾用卡莫司汀（BCNU）或鬼臼噻吩甙（VM-26）治疗。结果 全组中位生存11个月，1年生存率为40．79％，2年生存率为13．26％，有症状组与无症状组生存期差异无统计学意义。无症状组WBRT前中位化疗3周期（1～6周期），WBRT前接受3或4周期化疗者有预后意义（P=0．0188，P=0．0035）。无症状组治疗中并用BCNU或VM=26者生存期明显优于未用者（P=0．0219）。两组患者Ⅲ／Ⅳ度血液学毒性差异无统计学意义。COX多因素回归分析结果显示，脑转移灶数目（P=0．000）、脑外病灶数目（P=0．022）及ECOG状态（P=0．001）为独立预后因素。结论=无症状脑转移者WBRT前化疗3或4周期为宜，化疗可部分控制脑转移病灶，治疗中并用BCNU或VM-26可能有延长生存的优势。     

Benefits of postoperative radiotherapy in multimodality treatment of resected small-cell lung cancer with lymph node metastasis

Aim

The purpose of this study is to evaluate the role of postoperative radiotherapy (PORT) in resected small-cell lung cancer (SCLC).Methods: This study retrospectively analyzed 143 patients with completely resected SCLC in our institution between 1996 and 2011. The primary endpoint was overall survival (OS). The log-rank test and Cox regression model were used to evaluate the factors influencing local-regional recurrence (LRR) and OS.

Results

The median OS for the entire population was 34 months, and the 5-year OS rate was 34.6%. In multivariate analysis, age, surgical procedure, pathology stage, adjuvant chemotherapy and distant relapse were significant factors for survival. For the whole population, PORT had no effect on OS, with a median OS of 40 months in the PORT group versus 27 months in the non-PORT group (p = 0.260). However, in patients with N1 disease, the median OS were 40 months in the PORT group versus 14 months in the non-PORT group (p = 0.032). The corresponding OS in N2 patients were 35 months versus 17 months, respectively (p = 0.040). Similarly, PORT significantly reduced the LRR in patients with positive lymph node. For patients with N1 disease, the 3-year LRR rate was 0.0% in the PORT group versus 14.3% in the non-PORT group (p = 0.037). The corresponding LLR rate in N2 patients was 4.2% versus 56.6% (p < 0.001).

Conclusion

PORT significantly reduced LRR and improved OS in patients with regional metastasis SCLC. We suggest supplementing PORT in the multimodality treatment of resected SCLC with lymph node metastasis.     

全脑放疗对广泛期小细胞肺癌脑转移的生存影响

目的 探索现代诊疗条件下,全脑放疗（WBRT）能否延长小细胞肺癌（SCLC）脑转移患者的生存期。方法 回顾性分析天津医科大学肿瘤医院2010—2020年245例伴有脑转移的广泛期SCLC患者的病历资料,其中WBRT组168例（剂量30 Gy分10次）,无WBRT组77例。所有患者均接受了至少2个周期的化疗,化疗方案均为顺铂或卡铂联合依托泊苷,115例接受了胸部放疗。研究终点为脑转移后生存期（BM‐OS）,采用卡方检验对分类数据进行比较,采用稳健逆概率处理加权（sIPTW）方法对组间变量进行匹配,采用Kaplan‐Meier方法进行生存分析,log‐rank检验进行生存曲线比较。结果 全组患者中位BM‐OS为9.1个月。有无WBRT患者的中位BM‐OS分别为10.6、6.7个月（P=0.003）,应用sIPTW平衡两组影响因素后,两组的BM‐OS差异仍具有统计学意义（P=0.02）。其中,首诊广泛期伴脑转移患者118例,有无WBRT的中位BM‐OS分别为13.0、9.6个月（P=0.007）;广泛期疗中出现脑转移患者127例,有无WBRT的中位BM‐OS分别为8.0、4.1个月（P=0.003）。在50例单纯脑转移患者中,有无WBRT的中位BM‐OS为13.3、10.9个月（P=0.259）;在195例伴有颅外转移的患者中,有无WBRT的中位BM‐OS分别为9.5、5.9个月（P=0.009）。结论 广泛期小细胞肺癌脑转移患者行全脑放疗能够为患者带来生存获益。     

全脑放疗对广泛期小细胞肺癌脑转移的生存影响北大核心CSCD

目的探索现代诊疗条件下,全脑放疗(WBRT)能否延长小细胞肺癌(SCLC)脑转移患者的生存期。方法回顾性分析天津医科大学肿瘤医院2010—2020年245例伴有脑转移的广泛期SCLC患者的病历资料,其中WBRT组168例(剂量30 Gy分10次),无WBRT组77例。所有患者均接受了至少2个周期的化疗,化疗方案均为顺铂或卡铂联合依托泊苷,115例接受了胸部放疗。研究终点为脑转移后生存期(BM-OS),采用卡方检验对分类数据进行比较,采用稳健逆概率处理加权(sIPTW)方法对组间变量进行匹配,采用Kaplan-Meier方法进行生存分析,log-rank检验进行生存曲线比较。结果全组患者中位BM-OS为9.1个月。有无WBRT患者的中位BM-OS分别为10.6、6.7个月(P=0.003),应用sIPTW平衡两组影响因素后,两组的BM-OS差异仍具有统计学意义(P=0.02)。其中,首诊广泛期伴脑转移患者118例,有无WBRT的中位BM-OS分别为13.0、9.6个月(P=0.007);广泛期疗中出现脑转移患者127例,有无WBRT的中位BM-OS分别为8.0、4.1个月(P=0.003)。在50例单纯脑转移患者中,有无WBRT的中位BM-OS为13.3、10.9个月(P=0.259);在195例伴有颅外转移的患者中,有无WBRT的中位BM-OS分别为9.5、5.9个月(P=0.009)。结论广泛期小细胞肺癌脑转移患者行全脑放疗能够为患者带来生存获益。     

Prophylactic cranial irradiation in patients with small-cell lung cancer: the experience at the Institute of Oncology Ljubljana

Background

Prophylactic cranial irradiation (PCI) has been used in patients with small-cell lung cancer (SCLC) to reduce the incidence of brain metastases (BM) and thus increase overall survival. The aim of this retrospective study was to analyze the characteristics of patients with SCLC referred to the Institute of Oncology Ljubljana, their eligibility for PCI, patterns of dissemination, and survival.

Patients and methods

Medical charts of 357 patients with SCLC, referred to the Institute of Oncology Ljubljana between January 2004 and December 2006, were reviewed to determine characteristics of patients chosen for PCI. The following data were collected: age, gender, performance status (PS), extent of the disease, smoking status, type of primary treatment with outcome, haematological and biochemical parameters, PCI use, and finally brain metastases (BM) status at diagnoses and after treatment.

Results

PCI was performed in 24 (6.7%) of all patients. Six (25%) patients developed brain metastases after they were treated with PCI. Brain was the only site of metastases in 4 patients, two progressed to multiple organs. Median overall survival of patients with PCI was 21.9 months, without PCI 12.13 months (p = 0.004). From the collected data there were good prognostic factors: age under 65 years, limited disease (LD), performance status, normal levels of lactate dehydrogenase (LDH) and normal levels of C-reactive protein levels (CRP). Other prognostic factors did not show statistical significant values.

Conclusions

Survival of patients with LD, who have had PCI, was significantly better than those who had not. We decided to perform PCI in patients with LD, in those with complete or near complete response, and those with good performance status (≥ 80). We did not use PCI in extended disease (ED). The reason for that shall be addressed in the future. Doses for PCI were not uniform, therefore more standard approach should be considered.     

HTP方案联合全脑放疗治疗肺癌脑转移的临床观察

目的:评价羟基喜树碱、替尼泊甙和顺铂组成的HTP方案联合全脑放疗治疗肺癌脑转移的有效性和安全性。方法:34例肺癌脑转移患者,采取化疗-放疗-化疗的治疗顺序,即先接受HTP方案化疗2周期,第2周期化疗结束后休息2周,接受全脑放疗;放疗结束后休息2周,化疗有效和稳定的患者继续接受原方案化疗2~4周期。HTP方案具体用法为:羟基喜树碱(HCPT)6~8mg/d,静脉滴注,d1~d5;替尼泊甙(VM-26)100mg/d,静脉滴注,d1~d4;顺铂(PDD)20mg/d静脉滴注d1~d5。注意血象和造血细胞因子支持。每4周重复。放射治疗采用6MV-X线全脑照射,2Gy/次,每日1次,每周5日,DT30~46Gy。每2周期化疗结束行疗效评价。结果:完成化疗-放疗-化疗的患者共30例,客观CR0例,PR14例,SD12例,PD4例,有效率(CR PR)为46.7%,疾病控制率(CR PR SD)为86.7%。而单纯颅内病灶评价为:CR4例,PR21例,SD5例,PD0例,有效率(CR PR)为83.3%。20例伴神经系统症状者,完成化疗-放疗-化疗后,19例患者症状得到缓解,15例患者一般状况得到明显改善(KPS评分提高≥20分)。肿瘤进展时间(TTP)为2~32个月,中位TTP为7个月;总生存期(OS)为5~49个月,中位生存期(MST)为10个月。骨髓抑制和脱发是主要不良反应。结论:HTP方案联合全脑放疗对肺癌脑转移具有较好的疗效,生存期得到延长,值得进一步观察研究。     

Radiotherapy in small-cell lung cancer: lessons learned and future directions

Although chemotherapy is an essential component in the treatment of small-cell lung cancer, improvements in survival in the past two decades have been mainly achieved by the appropriate application of radiotherapy. The aim of the present study was to review the key developments in thoracic radiotherapy and prophylactic cranial radiotherapy and to discuss the rationale behind key ongoing studies in small-cell lung cancer.     

非小细胞肺癌后程加速超分割放疗疗效观察

目的：通过前瞻性的研究非小细胞肺癌（ＮＳＣＬＣ）后程加速超分割放疗的疗效，寻找ＮＳＣＬＣ的最佳治疗手段。方法：对１９９３年１月～１９９６年７月我院收治的７０例ＮＳＣＬＣ患随机分组研究。常规组３５例：用＾６０Ｃｏ或８Ｍｖ－ｘ，５次／Ｗ，２Ｇｙ／次，总剂量７０Ｇｙ／３５次／７～８Ｗ。后程加速超分割组３５例：放疗前程为常规分割，２Ｇｙ／次，４０Ｇｙ／２０次／４Ｗ后改野，５天／Ｗ，２次／天，１．８Ｇｙ／