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Biomedical subjects

G DeBoer

Publications and source records attributed to G DeBoer.

At least 19 recordsLinked to original sources
PubMed1992

Second primary malignancies following diagnosis of small-cell lung cancer.

PURPOSE AND METHODS: The records of 800 patients with small-cell carcinoma of the lung (SCLC) treated between 1971 and 1985 at University of Toronto-affiliated hospitals were reviewed for the occurrence and relative risk of second primary malignancies (SPMs). Almost all patients who developed a SPM were treated previously with chemotherapy and radiation therapy. RESULTS: Nineteen metachronous SPMs (MSPMs) and 11 synchronous SPMs (SSPMs) were identified. SSPMs were detected between 1 and 12 months after the diagnosis of SCLC. The MSPMs were identified between 1 and 10 years after the diagnosis of SCLC. MSPMs included non-small-cell lung cancer (NSCLC) (four patients), hematologic malignancies (HM) (three patients), and 12 with other solid tumors (OST). The median survival times after the diagnosis of MSPM was 33 months, 10 months, and 1 month, respectively, for those with NSCLC, OST, and HM. Expected cancer incidence rates were used to compute a relative risk rate for developing a MSPM in a subset of 392 patients on whom accurate follow-up information was available. The calculated relative risk for all tumors was 3.73. The relative risk for the development of secondary NSCLC was 6.83. CONCLUSION: We suggest that increased predisposition to SPM may relate to secondary effects of multimodality treatment and biologic considerations.

Aged↗
PubMed1991

P-glycoprotein expression as a predictor of the outcome of therapy for neuroblastoma.

BACKGROUND AND METHODS: Multidrug resistance in chemotherapy for cancer is characterized by increased genetic expression of P-glycoprotein, which acts as an ATP-dependent drug-efflux pump. To determine whether P-glycoprotein levels are of prognostic value in such cases, we measured these levels immunohistochemically in a retrospective study of sequential tumor samples from 67 children with neuroblastoma. RESULTS: P-glycoprotein was not detected in pretreatment samples from either of the 2 patients with Stage I disease, any of the 21 with Stage II disease, or any of the 8 with Stage IVS disease, but it was detected in the samples from 1 of the 17 patients with Stage III disease (6 percent) and 12 of the 19 with Stage IV disease (63 percent). Of the 44 patients with nonlocalized neuroblastoma (Stage III, IVS, or IV), 26 of the 31 who were negative for P-glycoprotein had a complete response to primary treatment, as compared with 6 of the 13 who were positive for P-glycoprotein (84 percent vs. 46 percent, P = 0.0232 by Fisher's exact test). Log-rank analysis of outcome, with simultaneous stratification according to tumor stage and age, showed that the group that was negative for P-glycoprotein had significantly longer relapse-free survival (P = 0.0011) and overall survival (P = 0.0373) than the group that was positive. CONCLUSIONS: Expression of P-glycoprotein before treatment may predict the success or failure of therapy for nonlocalized neuroblastoma. Neuroblastoma may be a promising tumor to treat with anticancer drug therapy combined with a chemosensitizing agent capable of reversing P-glycoprotein-mediated multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

The prognostic significance of pretreatment serum lactate dehydrogenase in patients with small-cell lung cancer.

Pretreatment serum lactate dehydrogenase (LDH) levels were assayed in 288 patients presenting with small-cell lung cancer (SCLC) between 1976 and 1985. Patients were routinely staged by physical examination, chest x-ray, bone, brain, and liver scans, and bone marrow evaluation. Clinical response and survival were assessed following treatment with combination chemotherapy as part of four clinical trials. Patients with extensive disease (ED) presented with a higher incidence (108 of 147, 73%) of abnormally elevated LDH (greater than 193 IU/L) than those (65 of 141, 46%) with limited disease (LD) (P = 2 x 10(-6)). Forty percent of patients had an initial normal LDH level and a higher response rate (89 of 108, 82%; complete response [CR], 47%) than those with elevated values of LDH (119 of 156, 76%; CR, 29%). The CR rate varied inversely with the level of LDH in patients with LD (P = .026) but not in those with ED (P = .300). The median survival time and 1-year and 2-year survival rates for patients with elevated LDH were 39 weeks and 33% and 6%, respectively, whereas for those with a normal LDH level these were 53 weeks and 54% and 16%, respectively. Patients with LD and elevated levels of LDH manifested a higher relative death rate (1.63:1) when compared with patients with LD and LDH in the normal range (P = .0083). The survival of patients with ED did not differ between those with normal and elevated levels of LDH (P = .273). A significant survival advantage persisted for patients with LDH in the normal range following adjustments for extent of disease, performance status (PS), and treatment protocol (P = .044, log-rank analysis). In conclusion, serum LDH appears to be a significant independent pretreatment prognostic factor in patients with SCLC that correlates with stage of disease, response to treatment, and survival.

Adult↗
PubMed1989

Nd-YAG laser-induced endobronchial burn. Management and long-term follow-up.

Endobronchial fires are a rare complication of Nd-YAG laser photoresection. Short-term morbidity is secondary to sloughing mucosa and mucous plugging. Aggressive pulmonary hygiene, including frequent bronchoscopies and possibly a tracheostomy, may be required. The major long-term complication is obstruction of the airways from granulation tissue. Long-term follow-up is required to evaluate and treat clinically significant granulation tissue in the airways.

Aged↗
PubMed1988

A randomized trial of two dose levels of cyclophosphamide, methotrexate, and fluorouracil chemotherapy for patients with metastatic breast cancer.

This study was designed to assess the role of dosage of chemotherapy for treatment of metastatic breast cancer. One hundred thirty-three patients without prior chemotherapy for metastatic disease were randomly allocated to receive two different dose levels of cyclophosphamide (C), methotrexate (M), and fluorouracil (F), administered intravenously (IV) every 3 weeks. Patients were stratified by sites of disease (visceral, bone, or soft-tissue dominant) and by interval from primary surgery to first recurrence. Doses on the higher-dose arm were 600 mg/m2 (C,F) and 40 mg/m2 (M) with escalation if possible; doses on the lower-dose arm were 300 mg/m2 (C,F) and 20 mg/m2 (M) without escalation. Patients who failed to respond to lower-dose CMF were crossed over to the higher-dose arm. Patients randomized to the higher-dose arm had longer survival measured from initiation of chemotherapy (median survival, 15.6 months v 12.8 months, P = .026 by log-rank test), but the effect of dose was of borderline significance (P approximately 0.12) when adjusted for a chance imbalance between the two arms in the time from first relapse to randomization, using the Cox proportional hazards model. Response rates (International Union Against Cancer [UICC] criteria) for patients with measurable disease were higher-dose arm: 16/53 (30%) and lower-dose arm: 6/53 (11%), (P = .03). Only one of 37 patients responded on crossover from the lower- to the higher-dose arm. Patients experienced more vomiting, myelosuppression, conjunctivitis, and alopecia when receiving higher doses of chemotherapy. A series of 34 linear analogue self-assessment scales were used to make detailed quality of life assessments on a subset of 49 patients. These scales confirmed greater toxicity in the immediate posttreatment period, but also a trend to improvement in general health and some disease-related indices, in patients receiving higher-dose chemotherapy. This trial suggests that better palliation is achieved by using full-dose chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Neurologic disorders in patients with small cell lung cancer.

In a series of 641 patients with small cell lung cancer, 189 (29.5%) had at least one neurologic disorder either at the time of presentation or during the subsequent clinical course of the cancer. The total number of neurologic disorders was 210, which included brain metastases (75.7%), meningeal carcinomatosis (6.7%), intramedullary metastases (2.4%), epidural metastases (11.0%), hyponatremia producing CNS symptoms (3.3%), and Eaton-Lambert syndrome (1.0%). The most common signs and symptoms were motor dysfunction and confusion. The overall survival of patients with any neurologic disorder was compared to that of patients without neurologic problems. There was no difference between the survival curves for the first year and a half, but patients without neurologic complications had a greater probability of long-term survival (log-rank P = 0.03). There were no statistically significant differences when this comparison was made according to stage of disease. When a neurologic disorder related to cancer occurred, the survival time from the date of that diagnosis was usually short. The neurologic disorder was the immediate cause of death in the majority of cases. In patients who achieved a complete remission, the administration of prophylactic cranial irradiation (PCI) significantly reduced the risk of developing brain metastases as the initial site of the relapse (log-rank P = 0.0034). After adjustment for performance status and extent of disease, the survival of complete responders treated with and without PCI was not significantly different. We conclude that neurologic complications are a frequent and serious problem in patients with SCLC.

Adult↗
PubMed1987

Predictive value of staging investigations in patients with clinical stage I malignant melanoma.

We reviewed the charts of 393 consecutive patients referred to the Toronto-Bayview Regional Cancer Centre and the Ontario Cancer Institute between January 1, 1978, and December 31, 1982, with clinical stage I malignant melanoma to determine the predictive value of routine staging investigations. The investigations reviewed included physical examination, liver function tests, radionuclide liver-spleen and bone scans, chest x-ray, whole-lung tomograms, CT chest scans, CT brain scans, and bipedal lymphangiograms. The clinical stage of nine patients was changed, eight as a result of physical examination and one as a result of lymphangiogram. No other investigations detected metastatic melanoma at referral. We recommend that staging investigations for patients referred with clinical stage I malignant melanoma be restricted to a complete physical examination and a baseline chest x-ray for all patients.

Humans↗
PubMed1986

Superior vena caval obstruction syndrome in small cell lung cancer.

In a series of 643 patients with small cell lung cancer (SCLC), 55 patients (8.6%) had signs or symptoms of superior vena caval obstruction syndrome (SVCO). Relatively long intervals from the onset of the first symptoms of SVCO to the start of therapy were observed, and invasive diagnostic procedures were safely performed in most patients. The pretreatment characteristics of patients with SVCO were not significantly different from those of patients without signs of the syndrome, and survival was similar in both groups. Patients with SVCO were usually treated first with induction chemotherapy, and prompt resolution of signs and symptoms occurred in the majority. Radiation was effective in controlling SVCO at relapse or after failure of initial chemotherapy. It was concluded that SVCO in patients with SCLC should be treated initially with systemic chemotherapy, as for other presentations of this disease. The current data do not support the commonly held view that SVCO in SCLC should be approached as an oncologic emergency.

Adult↗
PubMed1986

5-Fluorouracil, adriamycin, and mitomycin-C (FAM) in the treatment of inoperable adenocarcinoma of the lung.

Fifty-three patients with inoperable adenocarcinoma of the lung were treated with 5-fluorouracil, Adriamycin, and mitomycin-C (FAM) in two dose schedules: schedule 1--5-FU 600 mg/m2 days 1, 8, 29, and 36 and Adriamycin 30 mg/m2 days 1 and 29 and mitomycin-C 10 mg/m2 day 1 repeated every 8 weeks. Schedule 2--5-FU 600 mg/m2 and Adriamycin 30 mg/m2 days 1 and 22 and mitomycin-C 10 mg/m2 day 1, repeated every 6 weeks. There were 28 males and 25 females, median age 57 years. There were 11 patients with limited disease and 42 patients with extensive disease. Ten patients had ECOG performance status 0; 34, 1; 6, 2; and 3, 3. Ten patients (18.8%) achieved a partial response. Response was seen in four limited disease patients (36.3%) and only six extensive disease patients (11.9%). The median duration of response was 33 weeks (range 17-50 weeks), and the median survival of these patients was 89.7 weeks. Sixteen patients achieved stable disease with a median response duration of 22 weeks (range 8-91 weeks). The median survival of the entire group was 32.6 weeks. The FAM regimen was tolerated well, with only mild gastrointestinal symptoms and moderate myelosuppression. The granulocyte nadir was less than 1,000 in 8% of patients and 1,000-1,500 in 20%. Only 5% of patients had a platelet count under 100,000 and three patients required red cell transfusions during treatment. These results indicate that FAM chemotherapy may be administered as an outpatient with minimal toxicity and can cause objective tumor regression in patients with adenocarcinoma of the lung.

Adenocarcinoma↗
PubMed1986

Is bone marrow examination in small-cell lung cancer really necessary?

Of 403 patients with small-cell lung cancer, we identified by aspiration, biopsy, or both 67 with bone marrow involvement and found the two procedures to be complementary in detecting marrow involvement. The mean surface area of the positive biopsy specimens was significantly greater than that of a randomly selected group of negative biopsy specimens, suggesting that the larger the specimen, the greater the chance of detecting tumour. Patients with marrow involvement had only a slightly worse prognosis compared with other patients who had extensive disease. Only 7 of the 403 patients (1.7%) had extensive disease based on marrow involvement alone. Because bone marrow examination rarely changes the stage of cancer in noninvasively assessed patients, and has no impact on the tolerance of chemotherapy and only a small effect on length of survival, we do not recommend this procedure in the routine staging of small-cell lung cancer.

Biopsy↗
PubMed1986

First-line therapy with VP-16 and cisplatin for small-cell lung cancer.

VP-16 and cisplatin were used as first-line therapy in 31 patients with small-cell lung cancer (SCLC) in whom chemotherapy regimens that contained doxorubicin (Adriamycin [Adria Laboratories, Columbus, Ohio]) were contraindicated because of severe cardiac or hepatic disease. Eight patients who had cerebral metastases at presentation were also included in the study. There were 11 patients with limited disease (LD) and 20 with extensive disease (ED). Of the 28 evaluable patients, 12 (43%) had a complete response (CR) and 12 (43%) had a partial response (PR). Four patients (14%) failed to respond. The median duration of response (MDR) for LD patients was 39 weeks and for ED patients was 26 weeks. Patients with LD who responded (CR and PR) had a median survival time (MST) of 70 weeks (range, 28 to 232+ weeks), whereas ED patients who responded had an MST of 43 weeks (range, 17 to 68 weeks). Gastrointestinal toxicity was mild, but leukopenia and thrombocytopenia were common. Mild degrees of reversible nephrotoxicity occurred in 15 patients, but required discontinuation of cisplatin in only two. The results of this study are compared with several other recently published reports of VP-16 and cisplatin used as first-line therapy in SCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Limitations of urinary mutagen assays for monitoring occupational exposure to antineoplastic drugs.

The sensitivity of the Salmonella reversion test of Ames as a screen for accidental absorption of 17 antineoplastic agents by drug handlers was evaluated. Dilutions of each drug were added to agar inoculated with each of two Salmonella typhimurium strains (TA98 and TA100); control plates contained no test drug. Colonies were counted after incubation at 36 degrees C for 48 hours. The drugs were tested in the presence of a liver preparation to provide metabolic activation of mutagenicity. Urine samples collected from patients after doses of three mutagenic drugs were extracted and tested with the Ames test. For 11 of the 17 drug solutions, no mutagenic activity was seen, but many of these 11 were toxic to the organisms. The most highly mutagenic drugs were doxorubicin and cisplatin, with mechlorethamine, carmustine, dacarbazine, and cyclophosphamide exhibiting less mutagenic activity. Urine from patients treated with doxorubicin or cyclophosphamide showed mutagenicity, but the results suggested that the quantity of these drugs that would have to be absorbed to produce a definite reaction in urine is unlikely to be achieved by drug handlers who use standard precautions. Because of its lack of sensitivity and the potential effects of environmental and dietary factors on the results, this bacterial mutagenicity test should not be used routinely for detection of accidental absorption of antineoplastic drugs.

Antineoplastic Agents↗
PubMed1985

The value of staging and serial follow-up investigations in patients with completely resected, primary, cutaneous malignant melanoma.

The purpose of this study was to determine the value of staging and serial follow-up investigations in newly diagnosed patients with completely excised primary cutaneous malignant melanoma. We reviewed the records of the 393 patients with completely excised primary malignant melanoma who were referred to the Ontario Cancer Institute and the Toronto-Bayview Regional Cancer Centre between 1 January 1978 and 31 March 1982. Initial investigations included history and physical examination in all 393 patients, complete blood count (199 patients), liver function tests (198 patients), urinary melanins (159 patients), chest X-rays (345 patients), whole lung tomography (182 patients), radionuclide liver-spleen scans (207 patients), and bone scans (116 patients), bipedal lymphangiograms (78 patients), CT scans of the chest (59 patients), and CT brain scans (51 patients). The clinical stage of ten patients was changed as a result of history and physical examination or lymphangiogram. All other investigations failed to detect metastatic melanoma. Follow-up investigations included history and physical examinations, complete blood counts, liver function tests, radionuclide liver spleen and bone scans. History and physical examinations, chest X-rays and patients' awareness of abnormalities were responsible for detection of subsequent melanoma recurrences. All other tests failed to identify metastatic melanoma at the time of its occurrence. Therefore, we recommend that initial staging investigations be limited to history and physical examination with clinical photographs, and baseline chest X-ray. We recommend that subsequent follow-up include only history and physical examinations and chest X-rays.

Follow-Up Studies↗
PubMed1985

Etoposide (VP-16) and cisplatin: an effective treatment for relapse in small-cell lung cancer.

Seventy-eight patients with evaluable small-cell lung cancer (SCLC) were treated with etoposide (VP-16) and cisplatin after their disease failed to respond to, or relapsed after, induction combination chemotherapy, consisting primarily of cyclophosphamide, doxorubicin (Adriamycin), and vincristine (CAV). Twenty-four patients had limited disease (LD) and 54 had extensive disease (ED). In six (8%) patients, a complete response (CR) was achieved and in 37 (47%), there was a partial response (PR). The median duration of response for responding patients was 22 weeks (range, 4 to 50 weeks) for patients with LD and 18 weeks (range, 4 to 49 weeks) for those with ED. Twelve percent of patients demonstrated stable disease, and 33% of patients had progressive disease on treatment. The median survival times of LD patients achieving a CR or PR were 59 and 34 weeks, respectively, whereas the comparable figures for ED patients were 45 and 23 weeks, respectively. Gastrointestinal toxicity was mild, but myelosuppression, predominantly leukopenia and thrombocytopenia, was common. Mild to moderate nephrotoxicity occurred in 11 patients, but was reversible in all cases. Two febrile episodes occurred during periods of drug-induced neutropenia, but no other significant toxicities were identified. These results provide further evidence that VP-16 and cisplatin is an effective and tolerable combination chemotherapy regimen for SCLC resistant to CAV.

Adult↗
PubMed1985

Carcinoembryonic antigen: a useful prognostic marker in small-cell lung cancer.

Plasma carcinoembryonic antigen (CEA) was determined in 180 patients with small-cell lung cancer (SCLC) before treatment. An abnormal level (greater than or equal to 6 ng/mL) was found in 34% of patients tested. Patients with extensive disease (39/83) had a significantly higher frequency of abnormal CEA (P = .001) than those with limited disease (22/97). There was a strong correlation between obtaining an objective response--particularly a complete response (P = .00003)--and the absence of an elevated CEA. Patients with an abnormal CEA also had a shorter survival time (P = .0007) and the difference remained statistically significant after logrank adjustment for extent of disease and ECOG (Eastern Cooperative Oncology Group) performance status. There was also a negative correlation between survival time and the quantitative level of CEA. In this series, only the group of patients with normal initial CEA levels included all survivors beyond 2.5 years. We conclude that CEA is a useful prognostic factor in SCLC.

Adult↗
PubMed1979

Carcinoma of the esophagus: pretreatment assessment, correlation of radiation treatment parameters with survival, and identification and management of radiation treatment failure.

Between January 1969 and February 1975, 344 patients with carcinoma of the esophagus were managed primarily at the Princess Margaret Hospital, Toronto. One hundred sixty-eight (168) of the patients were treated palliatively and 176 of the patients were treated by radical doses of radiation, surgical resection or both. Survival of the radical treatment group was biphasic, the steeper component being identical to the survival of the palliative treatment group, thereby representing a group of patients that did not respond to radical treatment. Analysis of pretreatment assessment parameters indicated that all patients with T1 lesions (length less than or equal to 5 cm, circumference incomplete) and all patients with Stage I disease responded to treatment. Patients who were female, age greater than or equal to 70 years, N0 or had well differentiated squamous cell histology, responded to treatment in at least 80% of cases. No patient with extralymphatic distant metastases responded to treatment. The presence of other major disease did not affect response to treatment. Thirty patients had surgical resections and their survival was not significantly greater than the 146 patients who had radical radiation alone. Survival analysis revealed an optimum range of nominal standard dose (NSD) of 1602--1714 rets (median 1679 rets) for patients treated by radiation alone. An optimum port size (area) of 100--140 cm2 was observed for patients receiving 5000 rads and supervoltage irradiation gave a significantly improved survival in comparison with megavoltage irradiation. Sixty-seven percent (67%) of patients treated by radical doses or radiation developed esophageal strictures postradiation and on the basis of radiological, endoscopic or histological evidence 75% of these strictures were considered to be associated with the persistence of malignancy. On the basis of postmortem examinations (32) and death certificates there was overall an 80% failure to control the disease locally and 95% of strictures were associated with persistence of malignancy in the esophagus. Thirty-one of the 146 patients receiving radical radiation alone had palliation for esophageal obstruction following radiotherapy. The construction of a physiological bypass (e.g., colon) resulted in a mean survival of 215 days which was much longer than the survival observed with rigid esophageal tubes (35 days) or gastrostomy tubes (58 days).

Aged↗