Comparison of outcomes in patients with stage III versus limited stage IV non-small cell lung cancer

Department of Radiation Oncology, University of Rochester Medical Center, Rochester, New York, USA.
Radiation Oncology (Impact Factor: 2.55). 06/2011; 6(1):80. DOI: 10.1186/1748-717X-6-80
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Standard therapy for metastatic non small cell lung cancer (NSCLC) includes palliative systemic chemotherapy and/or radiotherapy. Recent studies of patients with limited metastases treated with curative-intent stereotactic body radiation therapy (SBRT) have shown encouraging survival. We hypothesized that patients treated with SBRT for limited metastases have comparable outcomes with those treated with curative-intent radiation for Stage III NSCLC.
We retrospectively reviewed the records of NSCLC patients treated with curative-intent radiotherapy at the University of Rochester from 2000-2008. We identified 3 groups of patients with NSCLC: stage III, stage IV, and recurrent stage IV (initial stage I-II). All stage IV NSCLC patients treated with SBRT had ≤ 8 lesions.
Of 146 patients, 88% had KPS ≥ 80%, 30% had > 5% weight loss, and 95% were smokers. The 5-year OS from date of NSCLC diagnosis for stage III, initial stage IV and recurrent stage IV was 7%, 14%, and 27% respectively. The 5-year OS from date of metastatic diagnosis was significantly (p < 0.00001) superior among those with limited metastases (≤ 8 lesions) versus stage III patients who developed extensive metastases not amenable to SBRT (14% vs. 0%).
Stage IV NSCLC is a heterogeneous patient population, with a selected cohort apparently faring better than Stage III patients. Though patients with limited metastases are favorably selected by virtue of more indolent disease and/or less bulky disease burden, perhaps staging these patients differently is appropriate for prognostic and treatment characterization. Aggressive local therapy may be indicated in these patients, though prospective clinical studies are needed.

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    • "The difference between the survival time of patients with stage III and stage IV NSCLC was not significant in the present study. Cheruvu et al (22) reported 146 cases of NSCLC. The 5-year survival rate of patients with stage III, stage IV and recurrent stage IV, starting from diagnosis, was 7, 14 and 27%, respectively. "
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    ABSTRACT: The application of high-dose irradiation to centrally-located lung tumors is generally considered to be of high risk in causing bronchial injury. The aim of the present retrospective study was to investigate the safety and efficacy of stereotactic body radiation therapy (SBRT) for patients with centrally-located lung tumors. In total, 28 patients who underwent SBRT for lung tumors within 2 cm of a major bronchus were retrospectively analyzed. The median total dose prescribed was 45 Gy (range, 36.3-52.5 Gy), the median fraction was 12 (range, 10-15) and the median dose per fraction was 3.6 Gy (range, 3-5 Gy). The median follow-up period for the surviving patients was 14 months (range, 10-41 months). The local control rate of SBRT was 100%, with a complete response (CR) rate of 32.1% (9/28); a partial response (PR) rate of 50% (14/28) and a stable disease (SD) rate of 17.9% (5/28). In total, 15 patients survived and 13 patients succumbed; 11 patients succumbed to tumor progression, one to congestive heart failure and one to a brain hemorrhage. The main side-effects included grade 2 esophagitis (17.9%; 5/28) atelectasis (10.7%; 3/28) and grade 2 late radiation pneumonitis (7.1%; 2/28). Severe late toxicity (≥ grade 3) was not observed in any patient. SBRT is an effective and safe therapy for centrally-located lung tumors.
    Oncology letters 04/2014; 7(4):1292-1296. DOI:10.3892/ol.2014.1815 · 1.55 Impact Factor
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    • "Study N Metastatic sites Treatments 1-year PFS 5-year OS University of Maryland [23] 72 Brain (metachronous) SRS 13.2% University of Maryland [24] 42 Brain (synchronous) SRS, TS, RT, CRT, HIGRT 21% Hopital Louis Pradel Hospices Civils de Lyon, Lyonnce [25] 51 Brain (synchronous) BS, TS, RT, CRT 42% (BS + others) versus 5% (BS only) * University of Rochester [26] 38 Multisite, 1–8 metastases HIGRT 14% Rush University Medical Center [27] 23 Multi-site, 1-2 metastases TS, RT, HIGRT 22% "
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    ABSTRACT: Metastatic non-small cell lung cancer (NSCLC) carries a dismal prognosis. Clinical evidence suggests the existence of an intermediate, or oligometastatic, state when metastases are limited in number and/or location. In addition, following initial curative therapy, many patients present with limited metastatic disease, or oligo-recurrence. Metastasis-directed, anti-cancer therapies may benefit these patients. A growing evidence-base supports the use of hypofractionated, image-guided radiotherapy (HIGRT) for a variety of malignant conditions including inoperable stage I NSCLC and many metastatic sites. When surgical resection is not possible, HIGRT offers an effective alternative for local treatment of limited metastatic disease. Early studies have produced promising results when HIGRT was delivered to all known sites of disease in patients with oligometastatic/oligo-recurrent NSCLC. In a population of patients formerly considered rapidly terminal, these studies report five year overall survival rates of 13-22%. HIGRT for metastatic NSCLC warrants further study. We call for large, intergroup, and even international randomized trials incorporating HIGRT and other metastasis-directed therapies into the treatment of patients with oligometastatic/oligo-recurrent NSCLC.
    Pulmonary Medicine 10/2012; 2012(12):480961. DOI:10.1155/2012/480961
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    • "Given the cost of such treatment, the added value of extended cetuximab therapy must be proven in appropriate randomised settings. Other well recognised areas of controversy that apply to all NSCLC RT strategies including the cetuximab trials, are the role of ENI [7,8,29], PET for staging and treatment planning [8,30-32], radiation dose escalation [8,18,22] and consolidation chemotherapy after chemoradiation [2,33]. The variations in the 6 studies reviewed here nicely illustrate the uncertainties around these issues. "
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    ABSTRACT: Treatment of non-small cell lung cancer (NSCLC) is challenging in many ways. One of the problems is disappointing local control rates in larger volume disease. Moreover, the likelihood of both nodal and distant spread increases with primary tumour (T-) stage. Many patients are elderly and have considerable comorbidity. Therefore, aggressive combined modality treatment might be contraindicated or poorly tolerated. In many cases with larger tumour volume, sufficiently high radiation doses can not be administered because the tolerance of surrounding normal tissues must be respected. Under such circumstances, simultaneous administration of radiosensitizing agents, which increase tumour cell kill, might improve the therapeutic ratio. If such agents have a favourable toxicity profile, even elderly patients might tolerate concomitant treatment. Based on sound preclinical evidence, several relatively small studies have examined radiotherapy (RT) with cetuximab in stage III NSCLC. Three different strategies were pursued: 1) RT plus cetuximab (2 studies), 2) induction chemotherapy followed by RT plus cetuximab (2 studies) and 3) concomitant RT and chemotherapy plus cetuximab (2 studies). Radiation doses were limited to 60-70 Gy. As a result of study design, in particular lack of randomised comparison between cetuximab and no cetuximab, the efficacy results are difficult to interpret. However, strategy 1) and 3) appear more promising than induction chemotherapy followed by RT and cetuximab. Toxicity and adverse events were more common when concomitant chemotherapy was given. Nevertheless, combined treatment appears feasible. The role of consolidation cetuximab after RT is uncertain. A large randomised phase III study of combined RT, chemotherapy and cetuximab has been initiated.
    Radiation Oncology 01/2012; 7(1):3. DOI:10.1186/1748-717X-7-3 · 2.55 Impact Factor
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