Comment on "Treatment of Non-small Cell Lung Cancer Stage IIIA: ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)" Response

University of South Florida, Tampa, Florida, United States
Chest (Impact Factor: 7.13). 10/2007; 132(3 Suppl):243S-265S. DOI: 10.1378/chest.07-1379
Source: PubMed

ABSTRACT Stage IIIA non-small cell lung cancer represents a relatively heterogeneous group of patients with metastatic disease to the ipsilateral mediastinal (N2) lymph nodes and also includes T3N1 patients. Presentations of disease range from apparently resectable tumors with occult microscopic nodal metastases to unresectable, bulky multistation nodal disease. This review explores the published clinical trials to make treatment recommendations in this controversial subset of lung cancer.Design, setting, and participants: Systematic searches were made of MEDLINE, HealthStar, and Cochrane Library databases up to May 2006, focusing primarily on randomized trials, with inclusion of selected metaanalyses, practice guidelines, and reviews. Study designs and results are summarized in evidence tables.
The evidence derived from the literature now appears to support routine adjuvant chemotherapy after complete resection of stage IIIA lung cancer encountered unexpectedly at surgery. However, using neoadjuvant therapy followed by surgery for known stage IIIA lung cancer as a routine therapeutic option is not supported by current published randomized trials. Combination chemoradiotherapy, especially delivered concurrently, is still the preferred treatment for prospectively recognized stage IIIA lung cancer with all degrees of mediastinal lymph node involvement. Current and future trials may modify these recommendations.
Multimodality therapy of some type appears to be preferable in all subsets of stage IIIA patients. However, because of the relative lack of consistent randomized trial data in this subset, the following evidence-based treatment guidelines lack compelling evidence in most scenarios.

    • "The current standard of care for most patients with IIIA-N2 NSCLC patients is concurrent chemoradiotherapy [37]. However, long-term outcomes with this treatment are poor, due to a high rate of distant metastases and of local recurrence. "
    39th ESMO Congress (ESMO); 09/2014
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    • "Most patients with stage IIIA (N2) and IIIB NSCLC cannot undergo complete surgical resection. Up-front concomitant platinum based chemotherapy and radiotherapy are currently recommended [4,5]. Cisplatin-based chemotherapy increases radiotherapy-induced cell lethal DNA lesions, along with eradication of distant micrometastases and some other cytotoxic e.g. "
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    ABSTRACT: Concomitant platinum-based chemotherapy and radiotherapy (CT-RT) is the recommended treatment for unresectable locally advanced stage III non-small cell lung cancer (NSCLC). We conducted a phase II study to evaluate the efficacy and safety of fractionated oral vinorelbine with cisplatin as induction CT followed by CT-RT. Patients with stage III NSCLC received 2 induction cycles of intravenous vinorelbine 25 mg/m2 and cisplatin 80 mg/m2 on day 1 and oral vinorelbine 60 mg/m2 on day 8. Responding patients received 2 more cycles of cisplatin 80 mg/m2 on day 1 and oral vinorelbine 20 mg on days 1, 3 and 5 concomitantly with radiotherapy 2 Gy daily, 5 days/week for a total of 66 Gy. Seventy patients, median age 61 years, were enrolled. Overall response rate (ORR) was 50.0%; Disease Control Rate was 81.42%. Median PFS was 14.58 months [95%CI, 10.97-18.75]. Median OS was 17.08 months [95%CI, 13.57-29.57]. One-year and 2-year survival rates were 68.6% [95%CI, 57.7-79.4] and 37%. One patient had a grade 3 pulmonary radiation injury and 26.5% had graded 1/2 esophagitis. In non-operable IIIA-IIIB NSCLC, the combination oral vinorelbine (fractionated fixed dose) plus cisplatin, during concomitant CT-RT, could offer a well-tolerated option, with comparable activity to I.V. vinorelbine-based chemoradiotherapy regimens.Trial registration: NCT01839032.
    BMC Cancer 03/2014; 14(1):231. DOI:10.1186/1471-2407-14-231 · 3.32 Impact Factor
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    • "Chemoradiotherapy is the standard treatment of locally advanced lung cancer which is associated with significant dose limiting toxicities like radiation pneumonitis (RP) and esophagitis.[12] In a dose escalation study of 109 patients, grade 2 to 3 pneumonitis was seen in 14.6% and this was associated with lung-dosimetric parameters such as the mean lung dose (MLD), volume of lung that received at least 20 Gy (V20), and the normal-tissue complication probability (NTCP) of the lung. "
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    ABSTRACT: The purpose was to determine the correlation of clinical factors and lung dose volume parameters with significant radiation pneumonitis (RP) in non-small cell lung cancer patients treated with combined modality therapy. Between January 2008 and December 2010, 52 patients of non-small cell lung cancer were treated with combined modality therapy with radical intent. Radiation pneumonitis was correlated with ipsilateral (V20 ipsi, V5 ipsi and MLD ipsi) and whole lung (V20, V5, and MLD) dose volume parameters. Clinical factors like pulmonary function tests (PFT), site of tumor, planning target volume, and type of treatment were also correlated with incidence of significant pneumonitis. Out of 52 patients, 35.3% developed grade 2 or more pneumonitis. On univariate analysis, factors significantly correlating with radiation pneumonitis were V5 (P = 0.002), V5 ipsi (P = 0.000), V20 (P = 0.019), V20 ipsi (P = 0.004), MLD (P = 0.008) and MLD ipsi (P = 0.008). On multivariate analysis, V5 ipsi was retained as the most significant factor. Concurrent chemoradiation caused significantly more RP than neoadjuvant chemoradiation (P = 0.004). A cutoff of 65% for V5 ipsi had a sensitivity of 65% and a specificity of 91%. The correlation between pneumonitis and dosimetric constraints has been validated. Adding ipsilateral V20, V5, and MLD to the classical total lung constraints identifies patients likely to develop pulmonary toxicity in patients undergoing chemoradiation.
    South Asian Journal of Cancer 03/2014; 3(1):13-5. DOI:10.4103/2278-330X.126503
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