Disease-specific survival for limited-stage small-cell lung cancer affected by statistical method of assessment.

BACKGROUND: In general, prognosis and impact of prognostic/predictive factors are assessed with Kaplan-Meier plots and/or the Cox proportional hazard model. There might be substantive differences from the results using these models for the same patients, if different statistical methods were used, for example, Boag log-normal (cure-rate model), or log-normal survival analysis. METHODS: Cohort of 244 limited-stage small-cell lung cancer patients, were accrued between 1981 and 1998, and followed to the end of 2005. The endpoint was death with or from lung cancer, for disease-specific survival (DSS). DSS at 1-, 3- and 5-years, with 95% confidence limits, are reported for all patients using the Boag, Kaplan-Meier, Cox, and log-normal survival analysis methods. Factors with significant effects on DSS were identified with step-wise forward multivariate Cox and log-normal survival analyses. Then, DSS was ascertained for patients with specific characteristics defined by these factors. RESULTS: The median follow-up of those alive was 9.5 years. The lack of events after 1966 days precluded comparison after 5 years. DSS assessed by the four methods in the full cohort differed by 0-2% at 1 year, 0-12% at 3 years, and 0-1% at 5 years. Log-normal survival analysis indicated DSS of 38% at 3 years, 10-12% higher than with other methods; univariate 95% confidence limits were non-overlapping. Surgical resection, hemoglobin level, lymph node involvement, and superior vena cava (SVC) obstruction significantly impacted DSS. DSS assessed by the Cox and log-normal survival analysis methods for four clinical risk groups differed by 1-6% at 1 year, 15-26% at 3 years, and 0-12% at 5 years; multivariate 95% confidence limits were overlapping in all instances. CONCLUSION: Surgical resection, hemoglobin level, lymph node involvement, and superior vena cava (SVC) obstruction all significantly impacted DSS. Apparent DSS for patients was influenced by the statistical methods of assessment. This would be clinically relevant in the development or improvement of clinical management strategies.

Decision analysis for prophylactic cranial irradiation for patients with small-cell lung cancer.

PURPOSE: Prophylactic cranial irradiation (PCI) has been shown to provide survival benefit in patients with limited disease small-cell lung cancer (LD-SCLC) who have achieved complete response. However, PCI may also produce long-term neurotoxicity (NT). The benefits and risks of PCI in LD-SCLC are evaluated. METHODS: We developed a decision-analytic model to compare quality-adjusted life expectancy (QALE) in a cohort of SCLC patients who do or do not receive PCI by varying survival rates and the frequency and severity of PCI-related NT. Sensitivity analyses were applied to examine the robustness of the optimal decision. RESULTS: At current published survival rates (26% 5-year survival rate with PCI and 22% without PCI) and a low NT rate, PCI offered a benefit over no PCI (QALE = 4.31 and 3.70 for mild NT severity; QALE = 4.09 and 3.70 for substantial NT severity, respectively). With a moderate NT rate, PCI was still preferred. If the PCI survival rate increased to 40%, PCI outperformed no PCI with a mild NT severity. However, no PCI was preferred over PCI (QALE = 5.72 v 5.47) with substantial NT severity. Two-way sensitivity analyses showed that PCI was preferred for low NT rates, mild NT severity, and low long-term survival rates. Otherwise, no PCI was preferred. CONCLUSION: The current data suggest PCI offers better QALE than no PCI in LD-SCLC patients who have achieved complete response. As the survival rate for SCLC patients continues to improve, NT rate and NT severity must be controlled to maintain a favorable benefit-risk ratio for recommending PCI.

Metastases in supraclavicular lymph nodes in lung cancer: assessment with palpation, US, and CT.

PURPOSE: To compare ultrasonography (US), computed tomography (CT), and palpation for diagnosing supraclavicular lung cancer metastases and to assess the effect of proved metastases on TNM stage and diagnostic work-up. MATERIALS AND METHODS: One hundred seventeen consecutive patients (91 men and 26 women; mean age, 64.0 years) underwent palpation, US, and CT of supraclavicular regions and chest and upper abdominal CT. Fine-needle aspiration cytologic (FNAC) analysis was performed in patients with nodes with a short-axis diameter of 5 mm or greater; cytologic diagnosis was used as the standard of reference. Sensitivities of palpation, US, and CT were compared with McNemar testing. Relationship between size and palpability of nodes with metastasis was evaluated with logistic regression. RESULTS: Supraclavicular metastases were diagnosed cytologically in 30 (26%) of 117 patients: eight (31%) of 26 patients with small cell lung cancer (SCLC) and 22 (24%) of 91 patients with non-small cell lung cancer (NSCLC). Sensitivities of US (1.00; 30 of 30 patients) and CT (0.83; 25 of 30 patients) for detection of metastases were significantly higher (P <.001 and P =.001, respectively) than that of palpation (0.33; 10 of 30 patients). Palpable nodes with metastasis (mean diameter, 25.2 mm) were significantly larger than nonpalpable nodes with metastasis (mean diameter, 13.7 mm) (P =.002). To have a 50% chance of being palpable, nodes with metastasis had to have a diameter of at least 22.3 mm. TNM stage was changed in three of 91 patients with NSCLC, and further invasive diagnostic procedures were prevented in 11 of such patients because it was proved that nonpalpable nodes had metastases. CONCLUSION: Supraclavicular lung cancer metastases were cytologically proved in 26% of patients. Nodes with metastasis were only palpable when markedly enlarged. US tripled the sensitivity of palpation for detection of metastases. Results of US and US-guided FNAC analysis can change the work-up in patients with lung cancer.

[Assessment of cognitive function after preventive and therapeutic whole brain irradiation using neuropsychological testing]. / Erfassung kognitiver Funktionen nach prophylaktischer und therapeutischer Ganzhirnbestrahlung mittels neuropsychologischer Testverfahren.

PURPOSE: Aim of this study was the assessment of neuropsychological changes after whole brain irradiation. PATIENTS AND METHOD: 64 patients were tested before, and 29 after whole brain irradiation, including 28 patients with small cell lung cancer (SCLC) before prophylactic cranial irradiation (PCI) and 36 patients with cerebral metastases before therapeutic cranial irradiation (TCI), as well as 14 patients after PCI and 15 after TCI (Table 1). Intelligence, attention and memory were assessed applying a 90-minute test battery of standardized, neuropsychological tests (Table 3). RESULTS: Patients with SCLC showed test results significantly below average before PCI (n = 28, mean IQ = 83, SD = 17). Neither after PCI, nor after TCI the tested neuropsychological functions decreased significantly (Tables 4, 5). A comparison between SCLC-patients with and without cerebral metastases before whole brain irradiation showed better test-results in patients with cerebral metastases and fewer cycles of preceding chemotherapy (Table 7). CONCLUSION: Neuropsychological capacity in patients with SCLC was impaired even before PCI. Possible reason is the preceding chemotherapy. Whole brain irradiation did not induce a significant decline of cognitive functions in patients with PCI or TCI. A decline in a longer follow-up nevertheless seems possible.

Prophylactic cranial irradiation revisited: cost-effectiveness and quality of life in small-cell lung cancer.

PURPOSE: To investigate the therapeutic usefulness and cost-effectiveness of prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer (SCLC) who had achieved a complete remission. METHODS: A retrospective chart review was undertaken of all patients diagnosed in Saskatchewan with SCLC between 1987 and 1998 inclusive. Patients who achieved a complete remission were divided into two groups, depending on whether they underwent PCI (PCI+ and PCI-, respectively). The quality-of-life-adjusted survival was estimated by the Q-TWiST method (quality time without symptoms and toxicity). The mean incremental costs per month of incremental OS were calculated in a cost-effectiveness analysis. RESULTS: Among the 98 complete remission patients, the median OS for PCI+ and PCI- patients was 20.0 and 19.0 months, respectively (p > 0.05, nonsignificant). The median disease-free survival was 14.7 and 10.0 months, respectively (p < 0.05). The difference in the mean Q-TWiST survival was significant (p < 0.01). The mean marginal cost was $18,834/PCI+ patient and $17,885/PCI- patient (p > 0.05, nonsignificant). The cost-effectiveness ratio was $70/mo of incremental OS if u(tox) and u(rel) (the utility coefficients to reflect the value of time in health states of toxicity and relapse) were assumed to be 1.0. CONCLUSION: PCI is a cost-effective treatment that improves the quality-of-life-adjusted survival for patients with a complete remission of SCLC.

Immunocytochemical assessment of bone marrow aspirates for monitoring response to chemotherapy in small-cell lung cancer patients.

Recent reports have suggested that tumour cell immunodetection in bone marrow of small-cell lung cancer patients is by far more frequent than found cytohistologically and may have clinical relevance. This study evaluates primarily the efficacy of chemotherapy as method of in vivo purging, but also the relationship of marrow involvement with survival. A total of 112 bone marrow aspirates from 30 chemo-naïve patients were stained twice using anti-NCAM antibodies, first at diagnosis and then after chemotherapy (24 patients) or at disease progression (six patients). Marrow contamination was associated with lower survival (P = 0.002), and was also detected in 7/17 patients conventionally staged as having limited disease. At multivariate analysis, marrow involvement was an independent factor of unfavourable prognosis (P = 0.033). The amount of tumour contamination, before and after chemotherapy, remained unchanged also in responders and even in the subset of patients with apparent limited disease. Following chemotherapy, bone marrow became tumour negative only in 25% of initially positive responders and in none of non-responders. Our results indicate that (i) chemotherapy is not effective in purging bone marrow even in chemo-responsive patients and (ii) a subset of patients with limited disease and negative bone marrow aspirates might have a more favourable prognosis.

A metastatic neuroendocrine anaplastic small cell tumor in a patient with multiple endocrine neoplasia type 1 syndrome. Assessment of disease status and response to doxorubicin, cyclophosphamide, etoposide chemotherapy through scintigraphic imaging with 111In-pentetreotide.

Extrapulmonary small cell and small cell neuroendocrine tumors of unknown primary site are, in general, aggressive neoplasms with a short median survival. Like small cell lung cancer (SCLC), they often are responsive to chemotherapy and radiotherapy. Small cell lung cancer and well differentiated neuroendocrine carcinomas of the gastrointestinal tract and pancreas tend to express somatostatin receptors. These tumors may be localized in patients by scintigraphic imaging using radiolabeled somatostatin analogues. A patient with anaplastic neuroendocrine small cell tumor arising on a background of multiple endocrine neoplasia type 1 syndrome is reported. The patient had a known large pancreatic gastrinoma and previously treated parathyroid adenopathy. At presentation, there was small cell cancer throughout the liver and skeleton. Imaging with a radiolabeled somatostatin analogue, 111In-pentetreotide (Mallinckrodt Medical B. V., Petten, Holland), revealed all sites of disease detected by routine biochemical and radiologic methods. After six cycles of chemotherapy with doxorubicin, cyclophosphamide, and etoposide, there was almost complete clearance of the metastatic disease. 111In-pentetreotide scintigraphy revealed uptake consistent with small areas of residual disease in the liver, the abdomen (in mesenteric lymph nodes), and posterior thorax (in a rib). The primary gastrinoma present before the onset of the anaplastic small cell cancer showed no evidence of response to the treatment. The patient remained well for 1 year and then relapsed with brain, lung, liver, and skeletal metastases. Despite an initial response to salvage radiotherapy and chemotherapy with carboplatin and dacarbazine, the patient died 6 months later.

Assessment of bone marrow involvement by magnetic resonance imaging in small cell lung cancer. No significant change of staging.

STUDY OBJECTIVE: This prospective study was performed in an attempt to evaluate (1) the rate of magnetic resonance imaging (MRI) demonstrating bone marrow (BM) abnormalities, (2) the correlation of these abnormalities with a pathologic malignant BM involvement, and (3) the possible modification of patients' usual disease staging in the light of these abnormalities. METHODS: After extensive staging investigations, patients' diseases were classified as limited or extensive. Dorsal and lumbar spine MRI was performed for second staging. RESULTS: Thirty-two patients were eligible for this study. In ten patients (31.2 percent), MRI showed abnormalities; in four of them, the BM sample from the posterior iliac crest was free from malignancy. Three of these four patients had extensive disease. The last patient, because he had limited disease, had biopsy at the site of MRI abnormalities; the biopsy specimen revealed a malignant involvement and therefore this patient, initially classified as having limited disease, was classified in the extensive disease group. In only 1 of 32 patients, BM-MRI data modified initial staging. CONCLUSIONS: The metastases disclosure yield of the MRI in the detection of medullar involvement is higher than BM biopsy but especially in patients with extensive disease. Therefore, MRI should not be considered in routine practice, in particular in patients with extensive disease.

A more objective staging of advanced prostate cancer--routine recognition of malignant endocrine structures: the assessment of serum TPS, PSA, and NSE values.

Bone scans, serum tissue-specific polypeptide antigen (TPS), prostate specific antigen (PSA), and neuron-specific enolase (NSE) were assessed in a total of 80 hormonally treated prostate cancer patients. Thirty-nine patients were free of osseous lesions; in 8 subjects, 3 or fewer scintigraphic hot spots were found; in 29 patients, more than 3 bone lesions were recorded. In 3 patients, a partial contribution of endocrine cell cancer structures was found, while in one patient, a homogeneous small cell carcinoma was detected at autopsy. Measurement of the serum PSA test showed a clear-cut rise from stage D0 subjects to stage D2 patients, with a small number of bone lesions (> or = 3). However, a relative decrease in the mean PSA level was measured with further progression in a number of hot spots in bone (> 3). Androgen threshold that is critical for the induction of the PSA (and PAP) expression seems to differ markedly in various cell subpopulations that arise during adenocarcinoma dedifferentiation. This fact explains not only the rise in serum PSA in the majority of progressive and previously castrated subjects after an initial period of hormonal responsiveness, but also a relative decline of androgen-dependent PSA expression with further tumor progression. Localized disease was accompanied with normal or just slightly elevated TPS concentration. In metastatic tumors, serum TPS values revealed a steady increase with the progression in bone. These data seem to reflect not only an increase in tumor proliferation rate with progressively transformed genome, but also the rise in the number of proliferating cells. The presence of nonepithelial transformed tumor structures, such as small cell cancer within a bulk of adenocarcinoma, reduces or normalizes numerical serotests values of both TPS and PSA even during tumor progression. The extent of such decline depends upon the bulk of the endocrine component. The assessment of the above parameters, especially when associated with elevated plasma NSE concentrations, may help in distinguishing an advanced adenocarcinoma with and without elements of malignant neuroendocrine structures. The proposed approach, modified by applying corresponding organ-specific markers, may be checked for its possible general use in staging protocols of various heterogeneous tumors.

[Clinical and economic evaluation of the initial assessment of small cell cancer of the lung. Alternatives to classic evaluation. LGTO. The Lyon Group of Thoracic Oncology]. / Evaluation clinique et économique du bilan initial des cancers du poumon à petites cellules. Alternatives à un bilan classique. GLOT. Groupe Lyonnais d'Oncologie Thoracique.

Alternatively to the usual evaluation summary, a characteristic of small cell lung cancer, is the probability of significant diffuse metastases; the prognosis is directly linked to the extent of these metastases. Moreover, the assessment of the initial extension becomes heavier and more costly as investigations continue and each new technology appears. In order to evaluate the contribution of each examination, a classification has been established as a function of the time-scale to obtain the results, of the technology involved, or whether the investigation is painful or not and any likelihood of iatrogenic side-effects. An assessment in three stages is proposed to achieve the most effective and cheapest diagnosis possible. In relation to the usual technique of assessment this sequential approach allows for a 27% reduction in the time-scale for the diagnosis of diffuse disease, 51.3% in terms of technical involvement, 46.3% in terms of pain and discomfort and 53.9% in terms of iatrogenic potential. At the same time a reduction in cost of 47.5% is observed.

Factors affecting treatment patterns of radiation oncologists in the United States in the palliative treatment of cancer.

A questionnaire was sent to 488 radiation oncologists in the United States and 268 replied. Each was given a brief account of three hypothetical patients (one with brain metastases, one with locally advanced lung cancer and one with bone metastases) and asked how they would approach the problems posed. Younger radiation oncologists (less than 46 years) treated patients with brain metastases with a smaller number of fractions and were more likely to view the case of locally advanced lung cancer as palliative. The aim of the radiation oncologist was related to the treatment pattern chosen, with the aim to extend life frequently related to higher total dose and number of fractions. When the amount of private funding was compared with dose, number of treatments, and whether the case was called palliative or not, no relationship was found.

Small cell lung cancer: radionuclide bone scans for assessment of tumor extent and response.

Radionuclide bone scans were performed before and during combination chemotherapy in 119 systematically staged patients with small cell carcinoma of the lung. Before therapy, 49 patients (41%) had positive scans. Scan positivity was significantly associated with the presence of metastatic tumor in the bone marrow, positive skeletal radiographs, and elevated serum alkaline phosphatase levels. Nonosseous distant metastases were significantly more likely to be detected as the number of areas of focal abnormalities on bone scan increased. The survival of patients with documented distant metastases in bone and nonosseous sites was significantly inferior to the survival of patients with limited disease, isolated osseous extensive disease, and extensive disease occurring only in nonbony sites. Of 36 patients with initially abnormal scans and tumor regression documented by other methods, scan findings improved in 24 (67%). In 26 (36%) of 72 scans in patients demonstrating disease progression in extraosseous sites, new areas of increased radionuclide uptake appeared. Improvement or worsening in follow-up scans was associated with nonbony tumor response or progression, respectively, 70% of the time. Serial bone scans provide reasonably accurate staging and prognostic information in patients with small cell lung cancer, although they are probably not sufficiently reliable to be used as the sole parameter in therapeutic decision-making.

The value of abdominal computed tomography in the pre-treatment assessment of small cell carcinoma of the lung.

Computed tomographic (CT) scans of the abdomen were obtained in 65 patients with biopsy-proved but untreated small cell carcinoma of the lung. Intra-abdominal metastases were found in 24 (37%), the majority being in the liver and adrenals. Abdominal CT before treatment is recommended as a part of the staging process in patients with small cell carcinoma of the lung, since extent of disease is relevant to prognosis.