The increased detection of small-sized peripheral non-small-cell lung cancer (NSCLC) has renewed interest in sublobar resection in lieu of lobectomy.
We conducted a multicenter, noninferiority, phase ...3 trial in which patients with NSCLC clinically staged as T1aN0 (tumor size, ≤2 cm) were randomly assigned to undergo sublobar resection or lobar resection after intraoperative confirmation of node-negative disease. The primary end point was disease-free survival, defined as the time between randomization and disease recurrence or death from any cause. Secondary end points were overall survival, locoregional and systemic recurrence, and pulmonary functions.
From June 2007 through March 2017, a total of 697 patients were assigned to undergo sublobar resection (340 patients) or lobar resection (357 patients). After a median follow-up of 7 years, sublobar resection was noninferior to lobar resection for disease-free survival (hazard ratio for disease recurrence or death, 1.01; 90% confidence interval CI, 0.83 to 1.24). In addition, overall survival after sublobar resection was similar to that after lobar resection (hazard ratio for death, 0.95; 95% CI, 0.72 to 1.26). The 5-year disease-free survival was 63.6% (95% CI, 57.9 to 68.8) after sublobar resection and 64.1% (95% CI, 58.5 to 69.0) after lobar resection. The 5-year overall survival was 80.3% (95% CI, 75.5 to 84.3) after sublobar resection and 78.9% (95% CI, 74.1 to 82.9) after lobar resection. No substantial difference was seen between the two groups in the incidence of locoregional or distant recurrence. At 6 months postoperatively, a between-group difference of 2 percentage points was measured in the median percentage of predicted forced expiratory volume in 1 second, favoring the sublobar-resection group.
In patients with peripheral NSCLC with a tumor size of 2 cm or less and pathologically confirmed node-negative disease in the hilar and mediastinal lymph nodes, sublobar resection was not inferior to lobectomy with respect to disease-free survival. Overall survival was similar with the two procedures. (Funded by the National Cancer Institute and others; CALGB 140503 ClinicalTrials.gov number, NCT00499330.).
Lung cancer is the leading cause of cancer mortality in the United States and worldwide. Previously, lung cancer was simplistically divided into non-small-cell lung cancer (NSCLC) and small-cell lung ...cancer. However, in the last decade, we have gone from a simplistic binary system of classifying lung cancer to defining NSCLC on the basis of molecular subsets. KRAS mutations represent the most common molecular change in NSCLC. The presence of KRAS mutation has been shown to be associated with a poor prognosis in NSCLC, but this is of little clinical utility. More important is determining the clinical utility of KRAS mutational analysis for predicting benefit of chemotherapy, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), anti-EGFR monoclonal antibodies, or other novel therapeutics. Current data does not support the routine use of KRAS mutational analysis for predicting chemotherapy benefit. Additionally, there was significant interest in using KRAS status to select patients for EGFR TKI and anti-EGFR monoclonal antibodies. However, the EGFR mutational status has demonstrated significant predictive value in the selection of patients for EGFR TKI therapy and is now the preferred test. An association between KRAS mutational status and benefit of anti-EGFR monoclonal antibodies has not been demonstrated in NSCLC. Here we review, in the context of NSCLC, the underlying biology of KRAS mutations, the predictive value of KRAS mutations for therapeutic intervention, and the integration of KRAS mutational testing into our current clinical paradigms.
The prevalence of small cell lung cancer (SCLC) has declined in the U.S. as the prevalence of tobacco use has declined. However, a significant number of people in the U.S. are current or former ...smokers and are at risk of developing SCLC. Routine histological or cytological evaluation can reliably make the diagnosis of SCLC, and immunohistochemistry stains (thyroid transcription factor‐1, chromogranin, synaptophysin, and CD56) can be used if there is uncertainty about the diagnosis. Rarely do patients present with SCLC amendable to surgical resection, and evaluation requires a meticulous workup for extra‐thoracic metastases and invasive staging of the mediastinum. Resected patients require adjuvant chemotherapy and/or thoracic radiation therapy (TRT), and prophylactic cranial radiation (PCI) should be considered depending on the stage. For limited‐stage disease, concurrent platinum‐etoposide and TRT followed by PCI is the standard. Thoracic radiation therapy should be started early in treatment, and can be given twice daily to 45 Gy or once daily to 60–70 Gy. For extensive‐stage disease, platinum‐etoposide remains the standard first‐line therapy, and the standard second‐line therapy is topotecan. Preliminary studies have demonstrated the activity of immunotherapy, and the response rate is approximately 10–30% with some durable responses observed. Rovalpituzumab tesirine, an antibody drug conjugate, has shown promising activity in patients with high delta‐like protein 3 tumor expression (approximately 70% of patients with SCLC). The emergence of these and other promising agents has rekindled interest in drug development in SCLC. Several ongoing trials are investigating novel agents in the first‐line, maintenance, and second‐line settings.
Implications for Practice
This review will provide an update on the standard therapies for surgically resected limited‐stage small cell lung cancer and extensive‐stage small cell lung cancer that have been investigated in recent clinical trials.
摘要
由于吸烟率的下降, 美国的小细胞肺癌（SCLC）发病率已开始下降。然而, 在美国, 相当多的人目前或以往是吸烟者, 因而有患SCLC的风险。常规组织学或细胞学评价能够可靠地做出SCLC的诊断, 如果诊断不确定, 可以采用免疫组织化学染色（甲状腺转录因子‐1、嗜铬粒蛋白、突触素和CD56）。很少有SCLC患者接受手术切除, 评估时需要对胸腔外转移和纵隔侵袭性分期进行细致检查。已进行切除术的患者需要接受辅助化疗和/或胸部放疗（TRT）, 并应根据分期考虑是否进行预防性颅脑放疗（PCI）。对于局限期疾病, 同时使用铂类‐依托泊苷和TRT并且随后采用PCI是标准疗法。治疗时应早期开始胸部放疗, 每天可给予患者两次放疗（至45Gy）或一次放疗（60‐70 Gy）。对于广泛期疾病, 铂类联合依托泊苷仍然是标准的一线疗法, 标准的二线疗法是拓扑替康。初步研究已经证明了免疫治疗的活性, 缓解率约为10‐30％, 在一些患者中观察到持久的缓解。抗体偶联药物Rovalpituzumab tesirine在高δ‐样蛋白3肿瘤表达的患者（SCLC患者约占70％）中表现出不错的活性。这些和其它潜在药物的出现重新激起了治疗SCLC药物开发的兴趣。几项正在进行的临床试验正在一线、维持和二线治疗背景下研究新药。
对临床实践的提示：本篇综述将提供关于最近临床试验中用于经手术切除的局限期小细胞肺癌和广泛期小细胞肺癌的标准疗法的最新情况。
The prevalence of small cell lung cancer has declined in the U.S. as tobacco use has declined; however, current and former smokers are at risk of developing small cell lung cancer. This article focuses on current and emerging treatment options for small cell lung cancer.
Purpose The significance of radiotherapy (RT) -associated cardiac injury for stage III non-small-cell lung cancer (NSCLC) is unclear, but higher heart doses were associated with worse overall ...survival in the Radiation Therapy Oncology Group (RTOG) 0617 study. We assessed the impact of heart dose in patients treated at our institution on several prospective dose-escalation trials. Patients and Methods From 1996 to 2009, 127 patients with stage III NSCLC (Eastern Cooperative Oncology Group performance status, 0 to 1) received dose-escalated RT to 70 to 90 Gy (median, 74 Gy) in six trials. RT plans and cardiac doses were reviewed. Records were reviewed for the primary end point: symptomatic cardiac events (symptomatic pericardial effusion, acute coronary syndrome, pericarditis, significant arrhythmia, and heart failure). Cardiac risk was assessed by noting baseline coronary artery disease and calculating the WHO/International Society of Hypertension score. Competing risks analysis was used. Results In all, 112 patients were analyzed. Median follow-up for surviving patients was 8.8 years. Twenty-six patients (23%) had one or more events at a median of 26 months to first event (effusion n = 7, myocardial infarction n = 5, unstable angina n = 3, pericarditis n = 2, arrhythmia n = 12, and heart failure n = 1). Heart doses (eg, heart mean dose; hazard ratio, 1.03/Gy; P = .002,), coronary artery disease ( P < .001), and WHO/International Society of Hypertension score ( P = .04) were associated with events on univariable analysis. Heart doses remained significant on multivariable analysis that accounted for baseline risk. Two-year competing risk-adjusted event rates for patients with heart mean dose < 10 Gy, 10 to 20 Gy, or ≥ 20 Gy were 4%, 7%, and 21%, respectively. Heart doses were not associated with overall survival. Conclusion Cardiac events were relatively common after high-dose thoracic RT and were independently associated with both heart dose and baseline cardiac risk. RT-associated cardiac toxicity after treatment of stage III NSCLC may occur earlier than historically understood, and heart doses should be minimized.
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