Induction chemoradiotherapy for advanced stage III non-small cell lung cancer: long-term follow-up in 42 patients

This multi-institutional phase II study was designed to assess the feasibility, efficacy, toxicity, and long-term survival of induction chemoradiotherapy followed by surgery in previously untreated patients with advanced stage III non-small cell lung cancer. Chemotherapy regimen included cisplatin 20 mg/m2 on days 1-5 and 29-33, and VP-16 40 mg/m2 on days 1-5 and 29-33. Radiotherapy (50 Gy in 25 fractions) began on day 1. Clinically downstaged patients underwent thoracotomy 3-5 weeks after the completion of radiotherapy. Forty-two eligible patients (ten stage IIIA and 32 IIIB) were followed for a median period of 64 months. The response rate was 81%, and 20 patients had a clinically good response. Twenty-one patients underwent thoracotomy. Nineteen patients had complete resections and there were seven pathologic complete responses. There were four treatment related deaths (all stage IIIBs). There were significant survival differences between stage IIIA versus IIIB patients (P = 0.028; median survivals, 24.9 vs. 11.1 months; 5-year survival rates, 20% vs. 8.3%), and patients that achieved pathologic complete response (CR) versus those that did not (P = 0.045; median survivals 30.1 vs. 11.1 months; 5-year survival rates, 28.6% vs. 8.3%). Although the induction chemoradiotherapy employed in this study was not appropriate for stage IIIB patients, it proved feasible in stage IIIA patients in whom it resulted in good 5-year survival rates. It also provided good survival rates in patients achieving pathologic CR.     

局限期小细胞肺癌海马保护脑预防性照射初步研究

目的 分析局限期小细胞肺癌放化疗后行海马保护的脑预防性照射(PCI)的可行性。方法 2016-2019年于浙江省肿瘤医院对进行PCI的小细胞肺癌患者随机分至常规组 22例与海马保护组 18例。根据RTOG 0933试验勾画靶区,海马保护组采用容积调强弧形治疗(VMAT)技术,放疗结束后对患者进行霍普金斯言语测试及脑MRI随访。结果 海马体积(4.01±1.57) cm³,海马回避区体积(20.13±4.14) cm³,海马保护区 域D100%为(7.19±0.38) Gy,Dmax为(14.38±1.18) Gy。霍普金斯言语测试中,放疗后1个月与放疗前(测试3、测试4、学习数、保留百分比)相比,以及放疗后1个月与放疗后(测试3、学习数)相比,海马保护组较常规组下降程度低。平均随访时间(17.00±8.47)个月,共 2例患者出现脑部转移,均为常规放疗组且转移灶位于海马保护区之外。结论 采用VMAT技术进行海马保护的PCI在剂量学上具有可行性,测试结果提示海马保护对于记忆的保护作用,值得临床上进一步推广。     

Neoadjuvant immunotherapy for resectable non-small cell lung cancer

Lung cancer is the malignant tumor with the highest morbidity and mortality in the world. In recent ten years, with the emergence of new drugs and the optimization of treatment mode, the treatment of lung cancer is entering an era of precision and individualization. Neoadjuvant therapy can reduce tumor size, degrade tumor stage, kill circulating tumor cells and micrometastases in the body, afford operation possibility, and benefit the long-term survival of patients. However, the traditional neoadjuvant chemotherapy combined with surgical treatment seems to have entered the bottleneck period of efficacy and is difficult to achieve breakthrough progress. At the same time, the amazing efficacy of immunotherapy is gradually innovating the treatment mode of lung cancer. In recent years, the research data of immune checkpoint inhibitors in the treatment of non-small cell lung cancer (NSCLC) shows an explosive growth. Immunotherapy has been applied to the first-line treatment of advanced NSCLC. Therefore, some clinical trials have applied immunotherapy to neoadjuvant treatment of resectable NSCLC patients. In this paper, the efficacy, possible mechanisms, potential risks and existing problems of neoadjuvant immunotherapy for resectable NSCLC patients are reviewed, and the future development direction of neoadjuvant immunotherapy is discussed.     

Radiation and chemotherapy for patients with stage III non-small cell lung cancer

Nearly 50,000 people in the United States will be diagnosed with stage III non-small cell lung cancer during the year 2000. Over the past 10 years, combined modality therapy has become the standard of care for primary treatment of most of these patients. Numerous studies and meta-analyses document an improvement in survival for patients with stage III disease treated with sequential chemotherapy followed by chest radiation, compared with radiation alone. Some more recent studies have shown a further improvement in survival when the chemotherapy and full-dose radiation are given concurrently. Acute toxicity is increased compared with sequential chemotherapy followed by radiation, but late toxicities seem similar. A current question under study is whether the use of initial chemotherapy followed by concurrent chemoradiotherapy will further improve median and overall survival compared with immediate concurrent therapy alone.     

Neoadjuvant chemotherapy in early-stage non-small cell lung cancer

Of the patients that undergo complete resection of early-stage non-small cell lung cancer (NSCLC), 30–60% will die. Postoperative adjuvant chemotherapy has yet to demonstrate an unequivocal benefit and there are significant difficulties in administering postoperative chemotherapy to patients with the significant comorbidities found in NSCLC. Currently, several trials are evaluating the role of preoperative chemotherapy in stage I and II NSCLC. This paper reviews the rationale for this approach and potential future developments.     

Neoadjuvant chemotherapy in early-stage non-small cell lung cancer

Of the patients that undergo complete resection of early-stage non-small cell lung cancer (NSCLC), 30-60% will die. Postoperative adjuvant chemotherapy has yet to demonstrate an unequivocal benefit and there are significant difficulties in administering postoperative chemotherapy to patients with the significant comorbidities found in NSCLC. Currently, several trials are evaluating the role of preoperative chemotherapy in stage I and II NSCLC. This paper reviews the rationale for this approach and potential future developments.     

Neurocognitive function in patients with small cell lung cancer : effect of prophylactic cranial irradiation

BACKGROUND: The use of prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC) has been tempered by fears of detrimental effects on cognitive function. Neuropsychologic testing was prospectively conducted before and after PCI to evaluate its effects on cognitive function in patients with SCLC. METHODS: Ninety-six patients who completely or partially responded to initial therapy underwent formal neurocognitive testing before PCI. Three patients who had central nervous system metastasis were excluded. Of the remaining patients, 69 received PCI (mean dose, 25 grays [Gy] in 10 fractions). Repeat testing was performed on 37 patients (median follow-up, 23 months; range, 6-120 months). RESULTS: Baseline impairment was defined as > or =1.5 standard deviations below the normative mean. Before undergoing PCI, 47% of patients had evidence of impaired cognitive function. After PCI, univariate analysis revealed significant transient declines in executive function (pre-PCI mean, 15.6 +/- 11.5; post-PCI, 27.1 +/- 17.6 [P = .008]) and language (pre-PCI mean, 33.8 +/- 9.9; post-PCI, 31.0 +/- 9.0 [P = .049]) at early timepoints. Controlling for noncentral nervous system disease progression the deficit in executive function was no longer significant. Moreover, these deficits were not sustained, and significant improvements in language and motor coordination were recorded. On multivariate analysis, no significant differences before and after PCI were found. CONCLUSIONS: Neurocognitive testing demonstrated that a substantial portion of patients with SCLC had impaired brain functioning at baseline. Persistent declines in cognitive function were not observed after cranial irradiation. These data do not favor the omission of PCI on the basis of fears of neurotoxic effects.     

Non-platinum induction chemotherapy for stage III non-small cell lung cancer

We conducted combination chemotherapy with gemcitabine (GEM) and paclitaxel (TXL) for stage III non-small cell lung cancer. The chemotherapy schedule consisted of GEM 800 mg/m2 and TXL 70 mg/m2 once a week for 6 consecutive weeks. The patients were 7 males and 3 females with a median age of 66 years. There were 5 adenocarcinomas and 5 squamous cell carcinomas, 7 stage IIIA and 3 IIIB. Eight patients completed 6 cycles of planned administration. Of 9 patients who were evaluable for response, 6 patients achieved PR (66.7%), 2 patients had SD, and 1 patient had PD. The cancers were resectable in 7 out of 9 patients, and were resected completely in 5 patients. Grade 3 anemia and leucopenia were observed in 1 patient and 2 patients, respectively, but they were mild. In our experience, a non-platinum weekly regimen with GEM and TXL is well tolerated and effective, which suggests the possibility of induction chemotherapy and outpatient treatment.     

Outcome of small cell lung cancer (SCLC) patients with brain metastases in a routine clinical setting

Background

Small cell lung cancer (SCLC) represents approximately 13 to 18% of all lung cancers. It is the most aggressive among lung cancers, mostly presented at an advanced stage, with median survival rates of 10 to12 months in patients treated with standard chemotherapy and radiotherapy. In approximately 15-20% of patients brain metastases are present already at the time of primary diagnosis; however, it is unclear how much it influences the outcome of disease according the other metastatic localisation. The objective of this analysis was to evaluate the median survival of SCLC patients treated by specific therapy (chemotherapy and/or radiotherapy) with regard to the presence or absence of brain metastases at the time of diagnosis.

Patients and methods

All SCLC patients have been treated in a routine clinical practice and followed up at the University Clinic Golnik in Slovenia. In the retrospective study the medical files from 2002 to 2007 were review. All patients with cytological or histological confirmed disease and eligible for specific oncological treatment were included in the study. They have been treated according to the guidelines valid at the time. Chemotherapy and regular followed-up were carried out at the University Clinic Golnik and radiotherapy at the Institute of Oncology Ljubljana.

Results

We found 251 patients eligible for the study. The median age of them was 65 years, majority were male (67%), smokers or ex-smokers (98%), with performance status 0 to 1 (83%). At the time of diagnosis no metastases were found in 64 patients (25.5%) and metastases outside the brain were presented in 153 (61.0%). Brain metastases, confirmed by a CT scan, were present in 34 patients (13.5%), most of them had also metastases at other localisations. All patients received chemotherapy and all patients with confirmed brain metastases received whole brain irradiation (WBRT). The radiotherapy with radical dose at primary tumour was delivered to 27 patients with limited disease and they got 4–6 cycles of chemotherapy. Median overall survival (OS) of 34 patients with brain metastases was 9 months (95% CI 6–12) while OS of 153 patients with metastases in other locations was 11 months (95% CI 10–12); the difference did not reach the level of significance (p = 0.62). As expected, the OS of patients without metastases at the time of primary diagnosis turned out to be significantly better compared to the survival of patients with either brain or other location metastases at the primary diagnosis (15 months vs 9 and 11 months, respectively, p < 0.001).

Conclusions

In our investigated population, the prognosis of patients with extensive SCLS with brain metastases at the primary diagnosis treated with chemotherapy and WBRT was not significantly worse compared to the prognosis of patients with extensive SCLC and metastases outside the brain. In extensive SCLC brain metastases were not a negative prognostic factor per se if the patients were able to be treated appropriately. However, the survival rates of extensive SCLC with or without brain metastases remained poor and novel treatment approaches are needed. The major strength of this study is that it has been done on a population of patients treated in a routine clinical setting.     

Neoadjuvant chemotherapy in invasive bladder cancer

The role of neoadjuvant chemotherapy in muscle-invasive bladder cancer has been clarified by recent randomized studies and meta-analyses, which all showed that cisplatin-based, combination chemotherapy offers a significant survival advantage. Preoperative chemotherapy results in downstaging in a significant percentage of patients, which is an independent factor of favorable prognosis. Nevertheless, the optimal sequence of perioperative chemotherapy remains undefined. The authors examine the results of large Phase II and randomized studies as well as the role of neoadjuvant chemotherapy in the context of bladder preservation strategies. Finally, issues of improving therapeutic efficacy and directing clinical research are discussed.     

Utilization of prophylactic cranial irradiation in patients with limited stage small cell lung carcinoma

BACKGROUND:

This study reports the adoption of prophylactic cranial irradiation (PCI) in patients with limited stage small cell lung carcinoma (LS‐SCLC) at Princess Margaret Hospital (PMH) and the factors that impact PCI utilization.

METHODS:

A retrospective review was performed on all patients with LS‐SCLC treated at PMH from 1997 to 2007. Clinical details including the rate of PCI utilization were determined and, for patients not receiving PCI, the documented reason was recorded. Brain failure free survival (FFS) and overall survival (OS) were estimated by the Kaplan‐Meier method, comparing patients treated with or without PCI. Pearson chi‐square test was used to determine factors associated with PCI use.

RESULTS:

Two hundred seven patients were treated for LS‐SCLC and 61.4% (n = 127) of these patients received PCI. The most common documented reason for not receiving PCI was patient refusal, typically because of concerns about PCI toxicity. Patients older than 65 were significantly less likely to receive PCI. Brain FFS and OS rates were significantly higher in patients who received PCI.

CONCLUSIONS:

Not all eligible patients are receiving PCI, despite its significant effect on reducing brain metastases and improving OS. Emphasizing the benefits of PCI to patients, when discussing potential toxicities, may improve utilization. Cancer 2010. © 2010 American Cancer Society.     

术后小细胞肺癌患者预防性脑照射研究进展

小细胞肺癌(SCLC)发病数较少,约占所有支气管肺癌的13%~20%,恶性程度较高,短时间内易复发转移。确诊时局限期小细胞肺癌约占SCLC的30%,符合手术患者仅占5%。放化疗后完全缓解者仍有一半以上患者发生脑转移。术后Ⅰ、Ⅱ、Ⅲ期SCLC患者脑转移发生率为6%~14%、13%~38%、11%~36%。预防性脑照射(PCI)可提高放化疗后完全缓解者总生存率,并降低脑转移发生率,是局限期SCLC综合治疗的重要组成部分。但是,PCI的临床应用仍存一些争议,手术完全切除的SCLC患者行PCI的疗效不一。本文对此问题进行文献综述,并介绍该领域的研究进展。     

Efficacy and safety of prophylactic cranial irradiation in patients with small cell lung cancer

Background: Prophylactic cranial irradiation (PCI) as part ofthe treament regimen for patients with limited stagesmall cell lung cancer (SCLC) remains controversial. Thepresent study was performed to analyze the efficacyand safety of PCI in patients with limitedstage SCLC who achieved complete remission.Patients and methods: Between 1983 and 1993, thirty-ninepatients with limited stage SCLC who had showncomplete remission after chemotherapy were enrolled prospectively intothe non-randomized study. Eighteen of them received PCI(PCI+), while 21 did not (PCI–). Pretreatment CTor MRI of the brain was performed inall patients. Patients were prospectively evaluated by aneurologist at regular intervals. Results: Three PCI+ patientsand seven PCI– patients developed brain metastases. Thefrequencies of brain metastases were not significantly differentbetween the groups (Fisher's exact test, p =0.207), but brain metastases in PCI+ patients tendedto occur later (log rank, p=0.008).Overall survival was significantly longer in PCI+ patients(log rank, p < 0.001).Early toxicity consisted of headache, nausea, fatigue, concentrationproblems and alopecia. These symptoms and signs weremild and usually reversible within a few months.Late toxicity was studied in patients whose survivalexceeded two years. Seven PCI+ patients survived formore than two years, while no PCI– patientssurvived for more than two years. Memory problemswere seen in six of the seven patients.These problems were non-disabling and, once established, remainedstable for months to years.The most prominent radiologic abnormalities were cortical atrophyand leukoencephalopathy, found in four of the fivepatients who underwent radiologic follow-up examination.Conclusions: This non-randomized study suggests that PCI maybe effective by decreasing the frequency of brainmetastases and by increasing the brain metastasis-free survivaland overall survival, with a minor risk ofclinical and radiologic neurotoxicity.     

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.     

小细胞肺癌放射治疗进展

目的 放射治疗是小细胞肺癌治疗的主要方式,其实施过程涉及到小细胞肺癌的诸多环节,总结国内外关于小细胞肺癌放射治疗的研究现状,探讨胸部放射治疗和全脑预防性照射在小细胞肺癌治疗中的价值.方法 应用PubMed、西文生物医学期刊文献数据库、中国知网及万方期刊全文数据库检索系统,以"小细胞肺癌,放疗,全脑预防性照射"为中文关键词,以"small cell lung cancer,radiotherapy,prophylactic cranial irradiation"为英文关键词,联合检索1996-01-2016-12的相关文献.共检索到英文文献377篇,中文文献4篇.纳入标准:(1)小细胞肺癌;(2)放疗;(3)全脑预防性照射.排除标准:(1)非小细胞肺癌;(2)手术;(3)化疗.根据剔除标准剔除中文文献2条,英文文献326条,最后纳入分析37篇文献.结果局限期小细胞肺癌的胸部放疗的分割剂量和模式为45 Gy/30次,超分割放疗或60~70 Gy/30~35次,常规分割放疗.胸部放疗参与的最佳时间为于化疗第1个周期或第2个周期参与.胸部同步放化疗结束以后行全脑预防性照射,放疗期间可给予药物盐酸美金刚以保护神经认知功能或海马保护的调强放射治疗;广泛期小细胞肺癌的胸部放疗的分割剂量和模式为30 Gy/10次或45 Gy/15次.全脑预防性照射存在争议.结论胸部放射治疗和全脑预防性照射在小细胞肺癌治疗中起着非常重要的作用.