Robert T. Eagan

Prognostic factors in patients with resected stage I non-small cell lung cancer. A report from the Lung Cancer Study Group.

The authors present prognostic information on recurrence and survival for resected Stage I lung cancer patients with squamous cell carcinoma, adenocarcinoma or large cell carcinoma. The data derive from 392 carefully staged patients and include results from the history and physical examination, preoperative laboratory tests, nature of the surgery, complications, initial pathologic findings following surgical resection, and final pathologic review. A simple multivariate model of recurrence, which is used to classify patients into low, intermediate, and high‐risk groups, is based on tumor size and location (T1, T2), histologic type (squamous, nonsquamous/mixed) and nodal status (N0, N1). To model survival, the performance status and the presence of empyema, pneumonia, or wound infection were added to the previous factors. Not all factors associated with increased mortality are associated with increased risk of recurrence, and, in particular, postoperative empyema, pneumonia or wound infections carry an increased risk of death only. Serial measurements of performance status and leukocyte count have the potential for monitoring for increased risk of recurrence and death.

Photoradiation therapy in the treatment of malignant brain tumors: a phase I (feasibility) study.

Hematoporphyrin derivative accumulates in malignant brain tumors and. when activated by light. can produce a cytotoxic reaction. A system for utilizing this concept in the treatment of human malignant brain tumors has been developed and tested in a small series of patients. No significant adverse re

Evaluation of response criteria in advanced lung cancer

Because we found it illogical to attempt measurement of nonmeasurable but visible tumors in patients with advanced lung cancer, we devised and used a separate set of response criteria for patients with evaluable, nonmeasurable tumors. Patients with evaluable disease who had obtained a tumor regression after therapy were compared to patients with measurable disease who had obtained a tumor regression according to standard criteria. Among 191 cases evaluated (54% with measurable and 46% with evaluable disease), 59 tumor regressions were found (35 in patients with measurable disease and 24 in patients with evaluable disease). Evaluating regressions in patients with both types of disease, we could not detect statistical differences in regression rates, times to regression, durations of regression or survival. We believe the response criteria used for patients with evaluable, nonmeasurable lung cancer to be valid in assessing response to therapy.

Limited-stage small-cell lung cancer: patterns of intrathoracic recurrence and the implications for thoracic radiotherapy.

PURPOSE This analysis was performed to determine the most appropriate volume that should be encompassed by thoracic radiation treatments (TRTs) for patients with limited-stage small-cell lung cancer (LSSCLC) who have responded to initial chemotherapy. PATIENTS AND METHODS A retrospective review of all patients (N = 67) with LSSCLC who were not entered onto a research protocol and were treated at our institution between the years of 1982 and 1990 was performed. Fifty-nine of 67 patients had adequate information regarding the size of the tumor before the start of chemotherapy (computed tomographic [CT] scan of chest or chest x-ray), the size of the tumor before TRT, and the TRT field size based on a simulation radiography. All 59 patients were treated with cyclophosphamide-based chemotherapy, and TRT was generally delivered concomitantly with chemotherapy following two to three cycles of chemotherapy alone. RESULTS Of 59 patients, 28 were treated with TRT field sizes that encompassed postchemotherapy tumor volumes, and 31 patients were treated with TRT field sizes that encompassed prechemotherapy tumor volumes (defined as a volume that included at least a 1.5-cm margin on the prechemotherapy tumor volume). Nineteen patients had an intrathoracic recurrence of disease as the first site of recurrent small-cell carcinoma: 10 of 31 patients treated with TRT fields that encompassed prechemotherapy tumor volumes and nine of 28 patients treated with TRT fields that encompassed postchemotherapy tumor volumes. For the 28 patients treated with TRT fields that encompassed postchemotherapy tumor volumes, the greatest distance that the prechemotherapy tumor volume (without margins) extended beyond the edge of the TRT field was 0.5 to 5.0 cm, with a median of 2.5 cm. All 19 of the intrathoracic recurrences were in-field failures, although two patients (one prechemotherapy volume and one postchemotherapy volume) did have concurrent pleural effusions. CONCLUSION These results indicate that the use of TRT fields that encompass postchemotherapy tumor volumes does not increase the risk of marginal failures or intrathoracic failures outside the TRT field.

Leukoencephalopathy in small cell lung cancer patients receiving prophylactic cranial irradiation

The cases of 283 small cell lung cancer patients who received treatment with combination chemotherapy with or without prophylactic cranial irradiation (PCI) were reviewed to determine the incidence of leukoencephalopathy. The overall incidence was 10%. Of all patients receiving PCI, 17% developed neurotoxicity, and of those receiving PCI and surviving ≥ 1.5 years, 37% suffered neurologic sequelae. In those receiving PCI but surviving<1.5 years, the incidence of neurotoxicity was 4%. The mean time interval between the end of PCI and the onset of neurotoxicity was 17 months (range 2–63 months). The PCI dose ranged from 2600–3600 cGy. None of the patients not receiving PCI developed neurotoxicity. The incidence of neurotoxicity in long-term survivors (≥1.5 years) with respect to PCI dose was ≤3000 cGy (25%), 3200 cGy (56%), 3600 cGy (36%). Almost all of the patients getting PCI also received lomustine, an agent associated with DNA repair inhibition and synergism with DNA damaging agents such as ionizing radiation or alkylating agents. Under the conditions of our study, PCI was associated with an unacceptable risk of neurotoxicity. Until further information is forthcoming, one should proceed with caution when using PCI in conjunction with lomustine.

The effect of CNS metastases on the survival of patients with small cell cancer of the lung

The records of 227 patients with small cell lung cancer (SMCLC) treated between January 1974 and July 1978 in a series of randomized trials were reviewed to determine the influence of central nervous system (CNS) metastases on survival. Sixteen patients were excluded because of single agent chemotherapy (11), lack of CNS irradiation despite proven metastases (2), prior chemotherapy (2), and concomitant metastatic second primary (1). Of 211 evaluable patients, 100 presented with limited disease and 111 with extensive disease, 25 of whom had CNS metastases at presentation, 21 (“CNS‐limited”) as the only site of metastases. Treatment of limited patients consisted of chemotherapy and thoracic radiation, while chemotherapy alone was used for extensive patients. No prophylactic brain irradiation was used, but CNS radiation was given to almost all patients when CNS metastases developed. Median survivals were: limited, 13.8 months; CNS‐limited, 15.1 months; and extensive 8.6 months (P <0.0001). There was no significant difference in the survival experience of limited and CNS‐limited patients, although none of the CNS‐limited patients experienced long‐term remissions. Thirty‐five of the limited patients and 21 of the extensive patients subsequently developed CNS metastases. Their median survivals following CNS metastases were 3.7 months and 1.6 months, respectively. In conclusion, CNS metastases as the sole site of metastatic disease at diagnosis of SMCLC is not necessarily a bad prognostic sign, while the subsequent development of CNS metastases may be.

Meningeal Carcinomatosis in Patients With Primary Breast or Lung Cancer

We reviewed the records of 35 patients with meningeal carcinomatosis and primary lung or breast cancer in an effort to identify prognostic factors. No definite associations were found. The prognosis for these patients continues to be poor; the median duration of survival after the diagnosis of meningeal carcinomatosis was 43 days in our study group.

Lack of value for cisplatin added to mitomycin-doxorubicin combination chemotherapy for carcinoma of unknown primary site. A randomized trial.

Fifty-five patients with metastatic carcinomas of unknown primary site (50 adenocarcinomas) were randomized, after stratification, to treatment with either mitomycin and dox-orubicin (MA) or mitomycin, doxorubicin, and cisplatin (MAP). There was a moderate but nonsignificant improvement in regression frequency (14 vs. 27%) and a slight but also nonsignificant worsening of survival (median 5.5 months vs. median 4.6 months) by the addition of cisplatin at 60 mg/m2 to the MA regimen.

Prophylactic cranial irradiation in complete responders with small-cell lung cancer: analysis of the Mayo Clinic and North Central Cancer Treatment Group data bases.

PURPOSE To determine whether prophylactic cranial irradiation (PCI) has an impact on brain failure and survival in patients with small-cell lung cancer (SCLC) who have achieved a complete response to chemotherapy with or without thoracic radiation therapy (TRT). METHODS Between 1975 and 1990, the Mayo Clinic and North Central Cancer Treatment Group entered 1,617 patients on 15 phase II and III SCLC protocols of chemotherapy with or without TRT and PCI. RESULTS Of 772 patients with limited disease, 457 (59%) achieved a complete response, compared with 200 of 845 patients (24%) with extensive disease. With follow-up durations of 2 to 17 years (median, 4), the median survival time and 2-, 5-, and 10-year survival rates for the 457 completely responding limited-disease (LD-CR) patients were 19.6 months, 41%, 17%, and 5%, compared with 13.9 months, 26%, 8%, and 5%, respectively, for the 200 completely responding extensive disease (ED-CR) patients (P = .0001). Multiple prognostic factors, including whether the patient did or did not receive PCI (30 to 38 Gy in 2- to 3.6-Gy fractions) were analyzed. In both univariate and multivariate analyses, PCI was not associated with improved (or worsened) survival. The brain relapse rate was 37% for LD-CR patients who did not receive PCI versus 9% for those who did (P = .0001). In ED-CR patients, the brain relapse rate was 31% without PCI and 8% with (P = .009). Essentially all patients who developed brain relapse died within 2 years, with a median survival time of 3.7 months following relapse. Severe, life-threatening, or fatal CNS toxicity occurred in approximately 3% of patients who received PCI. CONCLUSION The use of PCI remains controversial outside the setting of a clinical trial.

Results of combination chemotherapy and thoracic radiation therapy for unresectable non-small cell carcinoma of the lung.

From October 1979 to December 1982, 126 patients with locally advanced unresectable or inoperable Stage II (7 patients), Stage IIIA (81 patients), and Stage IIIB (38 patients) non-small cell carcinoma of the lung were treated in a prospective randomized trial using five cycles of CAP (Cytoxan, Adriamycin, and cisplatin), T-CAP (triazinate plus CAP), or V-CAP (VP-16 plus CAP) chemotherapy with thoracic radiation therapy (TRT). TRT consisted of 40 Gy in 10 fractions (split-course) with cycles 3 and 4 of chemotherapy. The treatment field included the primary tumor, ipsilateral hilum, mediastinum, and ipsilateral supraclavicular fossa. All patients were followed until death or for a minimum of 5 years for survivors. The evaluable subgroup consisted of 102 patients who completed TRT. Median and 5-year survivals for the entire group were 14.0 months and 10%, respectively; for the evaluable subgroup, they were 14.8 months and 12%, respectively. There was a trend toward better survival with V-CAP plus TRT than with CAP plus TRT (p = 0.08). Median and 5-year survivals were 16.2 months and 18%, respectively, with V-CAP plus TRT. Of eight prognostic variables analyzed for their association with survival, only Eastern Cooperative Oncology Group performance status (0,1 versus 2) (p = 0.02) and weight loss (less than or equal to 10% versus greater than 10%) (p = 0.05) were significant. Sex, age, T stage, N stage, overall stage, and histologic type were not significantly associated with survival. Failure analysis revealed 83 patients (81%) with identifiable first failures. The median time to first failure was 9.8 months, and the median survival after first failure was 4.7 months. Failure patterns included local failure alone (19%), local and distant (20%), and distant alone (43%). Nineteen percent of patients had no documented progression. Total failure patterns were local in 39% and distant in 63%. Twenty-three patients (23%) had failure in the brain; they accounted for 31% of all distant failures. In 20 of these patients (20% of all patients), this was the only site of failure. There were eight (8%) initial nodal failures in 96 untreated contralateral supraclavicular fossae. No initial failures were seen in any of 101 untreated contralateral hila. The data suggest the following: (a) Combined treatment with V-CAP and TRT yielded excellent results (median survival, 16.2 months; 5-year survival, 18%).(ABSTRACT TRUNCATED AT 400 WORDS)