Postoperative adjuvant chemotherapy in non‐small cell lung cancer: Prognostic value of DNA ploidy and postrecurrent survival

Ichinose, Yukito; Hara, Nobuyuki; Ohta, Mitsuo; Motohiro, Akira; Kuda, Tomoharu; Aso, Hiroshi

doi:10.1002/jso.2930460105

Cited by 30 publications

(11 citation statements)

References 10 publications

(9 reference statements)

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“…One study (Del Carlo Bernardi et al, 1997) defined diploid tumours as tumours presenting a DI ≤ 1.2 a feature shared by hypodiploid tumours Stipa et al, 1993). 3 publications were preliminary reports of DNA content-survival relationship (Salvati et al, 1989;Ichinose et al, 1991;Ogawa et al, 1991) but otherwise subsequently reported by the respective groups (Ogawa et al, 1992;Ichinose et al, 1993; Three studies included less than 10% small cell lung cancers.…”

Section: Resultsmentioning

confidence: 99%

Aneuploidy and prognosis of non-small-cell lung cancer: a meta-analysis of published data

Choma

Daurès²,

Quantin

et al. 2001

Br J Cancer

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Ploidy status predicts disease-free intervals and short-term survival in numerous human malignancies (Barlogie et al 1983; Friedlander et al 1984). In lung cancer, the prognostic value of ploidy is controversial. The effect of ploidy status on patient outcome has been investigated particularly in non-small-cell lung cancers (NSCLC), a group of different histologies including squamous cell carcinoma (SQC), adenocarcinoma (ADC) and large cell carcinoma (LCC). Although authors from different laboratories have suggested that patients presenting an aneuploid tumour have a shorter survival than patients presenting a nearly diploid tumour, others did not find such a difference. Many factors could explain the differences in estimating the ploidy-survival relationship. Possible interpretation could lie in the heterogeneity of the abnormal DNA patterns gathered under the common term of aneuploidy, i.e. hyperdiploidy, hypodiploidy and multiploidy . Differences in methods used to analyse DNA content could also have been responsible for the above-mentioned controversy inasmuch as some studies were founded on flow cytometry data whereas others used static cytometry. Finally, the difference might be related to the histological and clinical characteristics of the studied patient population.We therefore made a meta-analysis of published studies aimed at determining the prognostic effect of aneuploidy in surgically resected NSCLC. TRIALS AND METHODS Eligibility criteriaThe most conventional definition of ploidy status is as follows: ploidy was determined for each specimen using DNA index which represents the ratio of the cell DNA content of tumour G 0/1 cells to the diploid G 0/1 peak (2n). A coefficient of variation (CV) for this DNA index (DI) has been specifically defined for each study. Thus, a DNA index = 1 defined a near diploid specimen i.e. only one peak of G 0/1 cells in the near diploid region (2n, DNA index = 1) with few G 2 M tumour cells in the tetraploid region (4n Summary In lung cancer, DNA content abnormalities have been described as a heterogeneous spectrum of impaired tumour cell DNA histogram patterns. They are merged into the common term of aneuploidy and probably reflect a high genotypic instability. In non-small-cell lung cancer, the negative effect of aneuploidy has been a subject of controversy inasmuch as studies aimed at determining the survival-DNA content relationship have reported conflicting results. We made a meta-analysis of published studies aimed at determining the prognostic effect of aneuploidy in surgically resected non-small-cell lung cancer. 35 trials have been identified in the literature. A comprehensive collection of data has been constructed taking into account the following parameters: quality of specimen, DNA content assessment method, aneuploidy definition, histology and stage grouping, quality of surgical resection and demographic characteristics of the analysed population. Among the 4033 assessable patients, 2626 suffered from non-small-cell lung cancer with aneuploid DNA content ...

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Section: Resultsmentioning

confidence: 99%

Aneuploidy and prognosis of non-small-cell lung cancer: a meta-analysis of published data

Choma

Daurès²,

Quantin

et al. 2001

Br J Cancer

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“…Studies using DNA flow cytometry in non-small cell carcinoma have shown that aneuploidy reflects poorly on disease outcome. [3][4][5][6][7][8][9]37,38 These studies have shown that aneuploidy indicates higher incidence of recurrence, 7 poor short-term survival, 8 and lower overall survival rates. 6 Proliferative activity in non-small cell carcinoma of the lung has been less frequently reported in the literature.…”

Section: Discussionmentioning

confidence: 99%

“…5,39 In those studies where both ploidy and proliferative activity data were available in non-small cell carcinoma of the lung, ploidy seems to have more significant impact on predicting survival than proliferative activity. [3][4][5][6][7][8][9]37,38 Ploidy is not always the most important parameter in predicting malignant behavior in all organ systems. For instance, proliferative activity is more significant in predicting aggressive behavior in breast carcinoma than ploidy.…”

Section: Discussionmentioning

confidence: 99%

Cell Kinetics Analysis of Surgically Resected Non-Small Cell Carcinoma of the Lung Using the AgNOR Silver Stain

et al. 1997

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Cell kinetics analysis of lung carcinoma using DNA flow cytometry has shown a significant correlation with the biological behavior of these neoplasms. Ploidy has shown a more significant association with aggressive behavior. The method may however not be available in all centers. Two counts of the AgNOR silver stain have been correlated with ploidy and proliferative activity (PA). The first count, which is the mean number of AgNOR granules (mAgNOR), correlates with ploidy. The second count is the percentage of cells with ≥ 5 AgNORs/nucleus (pAgNOR), reflects PA. We performed the AgNOR silver stain using the two above-mentioned counts in 41 cases of surgically resected non-small cell carcinoma of the lung. The cases included 14 adenocarcinomas, 24 squamous cell carcinomas, and three undifferentiated non-small cell carcinomas. Follow-up data were available on 36 of the patients, ranging from 10 to 31 months (median 18 months). Thirteen of these patients (36%) developed progressive disease. Adenocarcinomas showed mAgNOR counts suggestive of aneuploidy (≥ 2.4) in nine of the 14 patients (64%) and 16 of the 24 squamous carcinomas (66%). The adenocarcinomas showed high pAgNOR counts (≥ 8%) in eight of the 14 cases (57%), in contrast to 15 of the 24 squamous carcinomas (62%). The AgNOR counts did not show any statistically significant correlation with tumor type, grade or stage of disease. The mAgNOR counts were aneuploid in all 13 progressive cases and in only 10 of the 23 stable cases (43%)(P=0.001). The pAgNOR counts were high in 12 of the 13 cases that progressed (92%), in contrast to 10 of the 23 stable cases (43%)(P=0.01). There is no significant evidence that squamous carcinoma of the lung may have a higher incidence of aneuploidy and high PA than adenocarcinoma. Our data also confirm previous data showing that aneuploid lung carcinomas have more aggressive behavior than diploid ones. This study also indicates that, despite the short-term follow-up data, the use of the AgNOR silver stain for cell kinetics analysis of non-small cell carcinoma of the lung may potentially provide useful predictive information on the biologic behavior of lung carcinoma. Long-term follow-up may provide more significant information.

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“…The composite fiveyear survival rate of the control arm patients (n = 486) was 55%. When examined individually, the treatment effects at five years for the five predominantly node-negative trials ranged from a 13% benefit for chemotherapy [10] to a 1% benefit for surgery alone [14]. There was no evidence of heterogeneity of effect between the trials (Q w =1.68, p = .79).…”

Section: Predominantly Node-negative Trialsmentioning

confidence: 94%

“…A recent meta-analysis suggests that early trials which employed alkylating agents in the postoperative setting have a detrimental effect on survival [9]. In the cisplatin era, 11 randomized trials have been reported [10][11][12][13][14][15][16][17][18][19][20]. The patient populations studied in these trials have varied from Stage I to Stage III, and many of the trials were designed and carried out in the early to mid-1980s, employing chemotherapy regimens and supportive care measures reflective of that time period.…”

Section: Introductionmentioning

confidence: 99%

Adjuvant Chemotherapy for Resected Non‐Small Cell Carcinoma of the Lung: Why We Still Don't Know

et al. 1998

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The role of adjuvant chemotherapy in resected non‐small cell carcinoma of the lung (NSCLC) remains controversial. A critical review of the 11 cisplatin‐based randomized trials addressing this issue was performed using methodology adapted from the CONSORT statement. The 11 trials were divided into those that included predominantly node‐negative patients (n = 5) and those that included predominantly node‐positive patients (n = 6). In the node‐negative trials, which included 1,084 evaluable patients, no evidence of heterogeneity of treatment effect between the trials was found. The composite five‐year survival rate for chemotherapy patients was 61% versus 55% for control patients, which reached marginal significance (p = 0.06). In the node‐positive trials, which included 880 evaluable patients, a marginal lack of homogeneity of treatment effect between trials was found (p = .013). The composite two‐year survival rate for chemotherapy patients was 48% versus 40% for control patients, which reached marginal significance (p = 0.06). Although not definitive, these trials suggest a benefit to postoperative adjuvant chemotherapy in resected NSCLC. The cumulative experience of the 11 trials is notable for: A) the small number of patients; B) heterogenous patient populations; C) substandard chemotherapy regimens; D) inadequate chemotherapy delivery, and E) less than optimally executed clinical trials. The 11 trials are discussed in detail, and recently completed and ongoing trials of adjuvant chemotherapy in resected NSCLC are reviewed.

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Postoperative adjuvant chemotherapy in non‐small cell lung cancer: Prognostic value of DNA ploidy and postrecurrent survival

Cited by 30 publications

References 10 publications

Aneuploidy and prognosis of non-small-cell lung cancer: a meta-analysis of published data

Aneuploidy and prognosis of non-small-cell lung cancer: a meta-analysis of published data

Cell Kinetics Analysis of Surgically Resected Non-Small Cell Carcinoma of the Lung Using the AgNOR Silver Stain

Adjuvant Chemotherapy for Resected Non‐Small Cell Carcinoma of the Lung: Why We Still Don't Know

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