Introduction
Locally advanced lung cancer (LA-LCa) remains a significant source of morbidity and mortality. Only carefully selected patients with T4N0-1M0 non-small cell lung cancer (NSCLC) may be considered for curative surgery, and individuals with N3 nodal involvement are not.Reference Jett, Schild, Keith and Kesler1 Hence, it is not unlikely that many individuals will receive palliative treatment.
Despite the administration of concurrent chemoradiotherapy, the prognosis in patients with LA-LCa remains poor. Estimating the prognosis of cancer patients with incurable disease remains a difficult task, and clinicians have repeatedly been shown to be poor at predicting survival. The description of long-term (LT) survivors after accepted therapeutic interventions are delivered in this particular patient subset has not generated much attention. In this retrospective study, we aimed to increase our understanding of the clinical characteristics of such advantaged people.
METHODS AND RESULTS
One hundred eighty-nine individuals diagnosed with mostly stage III NSCLC between August 1997 and January 2008 were identified from a review of the radiation oncology and cancer center databases. Of these individuals, seven (4%) patients with T4 and/or N3 disease survived for 5 years or longer after treatment. Primary tumors were defined as T4 lesions based on tumor involvement of the superior vena cava (four patients), extension into the mediastinum (one patient) or the presence of satellite lesions in the same lobe (one patient). Regional N3 nodal abnormalities were present in the supraclavicular space or contralateral mediastinal area.
Palliative megavoltage external beam irradiation of the intrathoracic neoplasm and the mediastinum with inclusion of clinically evident supraclavicular disease was applied. Radiation treatment planning technique, either two-dimensional (2D; using orthogonal radiographs) or 3D; computed tomography (CT)-aided), was dependent on time period of irradiation – pre-CT or CT era. The primary or nodal neoplasms were outlined based on accepted CT criteria of abnormality or very avid radionuclide uptake as visualized on positron emission tomography; the tumor volumes were calculated using the formula π/6 (width) (length) (height). The two-drug chemotherapy regimen generally consisted of cisplatin and etoposide, with the substitution of carboplatin instead of cisplatin in patients with impaired renal function. Response to treatment was assessed after completion of irradiation according to the RECIST criteria.Reference Therasse, Arbuck and Eisenhauer2 Survival was estimated from the time of diagnosis until death.
The clinical characteristics of this fortunate cohort are summarized in Table 1. Three individuals were women and four were men. The median age was 56 years. The presenting complaints included chest or arm pain, shortness of breath, cough, >10 pounds weight loss and dyspnea. Most of the patients were symptomatic at the time of diagnosis (5/7), had a gross tumor volume of >100 cc (5/7), and non-small cell cancer histologic type (4/7). In addition, many of these LT survivors received chemotherapy (5/7) and a dose that ranged from 30 to 60 Gy (mean dose 49 Gy); some individuals were treated to a lower dose because of the belief that the prognosis is poorer when superior vena caval obstruction is presentReference Bulbul, Oztua, Topbas and Ozlu3 or when the gross tumor volume is excessively large, and that the tumor is more radioresponsive when the histologic type is small-cell lung cancer.Reference Michaud, Chen and Daly4 All of the patients subjectively and objectively responded to treatment. The overall median survival time was 70 months.
Table 1 Patient, tumor and treatment characteristics
Notes: a American Joint Committee on Cancer staging system.
b Gross tumor volume estimation using the formula: π/6 (width) (length) (height).
c 2D, two-dimensional treatment planning; 3D, three-dimensional treatment planning.
d Cisplatin and etoposide drugs.
Abbreviations: NSCLC, non-small cell lung cancer; SCLC, small-cell lung cancer; NK, not known.
DISCUSSION
Analysis of our 11-year experience of 189 LA-LCa cases yielded a 5-year survival rate of 4% (a finding not inconsistent with the ≤1% reported in the literatureReference MacManus, Wada, Matthews and Ball5–Reference Wang, Nelson, Bogardus and Grannis7). The present study confirms observations from accounts of LT survivors that aggressive therapy is beneficialReference Wang, Nelson, Bogardus and Grannis7 and radiation dose may not be a significant prognostic factor.Reference MacManus, Wada, Matthews and Ball5 On the other hand, the mean age of such fortunate people has been 60 to 65 years,Reference Wang, Nelson, Bogardus and Grannis7 which is unlike the median age of 56 years in this limited study. Some clinical features with a connotation of an adverse outcome (like a larger tumor volumeReference Vos, Dahele, Dickhoff, Senan, Thunnissen and Hartemink8 or poor performance statusReference MacManus, Wada, Matthews and Ball5) did not have a significant impact on prognosis in our patients.
This report about a selected lung cancer population of T4 and N3 disease can only add to the sparse literature about LT survival (Table 2).Reference MacManus, Wada, Matthews and Ball5–Reference Wang, Nelson, Bogardus and Grannis7 Meaningful comparisons with the published data about clinicopathological characteristics deemed potentially influential toward prolonged survival are difficult mainly because the extent of disease has varied.
Table 2 Long-term survivalFootnote a of patients with NSCLC: review of the literature
Notes: a ≥5-year survival.
b Eighty percent of the patients possessed stage IIIA-B disease.
c Included some patients who were diagnosed with small-cell lung cancer and treated with chemotherapy.
Abbreviations: NSCLC, non-small cell lung cancer; LT=long term.
The benefit of radiotherapy with chemotherapy, in terms of prolonged survival, in select patents with LA-LCa has not been firmly realized. In conclusion, in light of the described results, 5-year survival (including symptom palliation) can be successfully effected by standard therapy. We believe that such a potential achievement indicates that treatment of these disease subsets is worthwhile.
