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Immunohistochemical detection of antigen in human primary and metastatic melanomas by the monoclonal antibody 140.240 and its possible prognostic significance.
An indirect immunofluorescence technique was used to study the tissue distribution of the epitope recognized by the monoclonal antibody 140.240 which identifies a p97-like melanoma-associated oncofetal antigen. Cryostat sections of various normal and neoplastic human tissues were examined. The presence of antigenic activity was demonstrated in 20 of 39 (51%) primary skin melanomas, in 21 of 52 (40%) metastatic melanomas, and in 20 of 44 (45%) nevi. The reactive nevi were restricted to intradermal, junctional, compound and spindle cell types. Of the 110 samples of 12 major tumor types other than melanoma tested, only 1 of 6 epidermoid tumors, 1 of 4 benign breast tumors and 1 of 5 prostatic tumors gave weak staining. This antibody also reacted with sweat glands and fetal small intestine tissue, but not with other adult or fetal normal tissues. Intrapatient as well as interpatient heterogeneity in the epitope expression was present in primary as well as metastatic tumor lesions surgically removed from patients with melanoma. Evaluation of the immunohistologic data and the clinical outcome of patients with melanoma reveals that the expression of the epitope recognized by this antibody is associated with a more favorable prognosis.
Chemotherapy of disseminated germ cell tumors.
The treatment of patients with germ cell neoplasms has improved dramatically during the last 10 years. Combination chemotherapy with cisplatin + vinblastine + bleomycin (PVB) was initiated at Indiana University in 1974. In this original study 28 of 47 patients (60%) with disseminated testicular tumors are currently alive, with a minimal follow-up of 10 years. Our next PVB study demonstrated that the vinblastine dosage could be reduced 25% (0.4 mg/kg to 0.3 mg/kg), thereby significantly reducing toxicity, without compromising the cure rate. Our third generation study confirmed the fact that maintenance therapy was not necessary, and that optimal cure rates could be achieved with merely 12 weeks of PVB induction. Overall, with follow-up of 5 to 10 years, 202 of 272 patients (74%) with disseminated testicular cancer currently are alive on these three PVB protocols. Because of the success of salvage chemotherapy, demonstrating that approximately 25% of patients not curable by PVB achieved durable complete remissions (CRs) with cisplatin + VP-16 combination chemotherapy, our next study compared PVB to cisplatin + VP-16 + bleomycin (PVP16B) as initial chemotherapy for disseminated testicular cancer. This study demonstrated that the two induction regimens produced equivalent CR rates, but that PVP16B was the preferable induction regimen because of a statistically significant reduction in neuromuscular toxicity. Our current studies will evaluate whether three courses (9 weeks) of PVP16B compared to the standard four courses of PVP16B (12 weeks) will achieve similar cure rates in minimal moderate disseminated disease. In advanced disease presentations, we are comparing standard PVP16B to double-dose cisplatin (40 mg/M2 X 5) + VP-16 + bleomycin.
TNM classification of malignant tumors. A comparison between the new (1987) and the old editions.
A major revision of the tumor, nodes, metastasis (TNM) classification has been published. It eliminates previous differences between the International Union Against Cancer (UICC) and American Joint Committee on Cancer (AJCC) versions. It also updates existing site classifications and adds chapters on previously unclassified tumors. This article summarizes the major changes from the past to the present editions of the TNM classification.
Advances in imaging.
The introduction of sonography, x-ray computed tomography, magnetic resonance imaging (MRI), and magnetic resonance spectroscopy (MRS) have enhanced the radiologist's ability to delineate and stage neoplasms in all parts of the human body. Images of excellent quality can be generated within a reasonable time frame and with minimal biologic risk. All of the more sophisticated imaging modalities are costly and none can, isolated from clinical data, provide histologic diagnoses. Within the next few years it is anticipated that the speed of magnetic resonance image acquisition will increase and that contrast agents for MRI will be brought into clinical use. Evaluation of cost-effectiveness will continue and new diagnostic algorithms can be expected to evolve.
Changes in serum levels of Forssman-like antibody in patients with gastric cancer.
Because Forssman antigen, one of the most well-known heteroantigens, has been noted in certain cancerous tissues, it would seem that the serum levels of the Forssman antibody of patients with these cancers would be low, owing to the absorption of the naturally occurring antibody by the Forssman antigen-containing cancerous tissues. This hypothesis was tested by researchers assessing the serum hemolysin titers of 174 patients with cancer (gastric cancer, 100; colonic cancer, 40; and other cancers, 45) and of 856 age-matched, sex-matched, and blood type-matched healthy individuals against the serum levels of sheep red blood cells. Serum levels of the hemolysin of patients with gastric cancer tend to be lower than those of patients with other types of cancer and also lower than those of age-matched and sex-matched controls. The decrease was especially prominent in patients with moderately differentiated adenocarcinoma of the stomach. Preoperative and postoperative serum samples of 40 patients with gastric cancer were analyzed therefore to determine the effect of surgically removing the cancer on the serum level of the hemolysin. The results showed that the serum levels of the hemolysin antibody increased in all 40 patients after the successful surgical removal of the cancer. However, in patients with recurrence of the cancer, the serum levels of hemolysin decreased again in 11 of 11 patients. These results indicate that the serum levels of the Forssman-like hemolysin could be used as an index of recurrence in patients with gastric cancer after surgical removal of the cancer.
Quality assurance in cancer care. Pathology.
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Chemotherapy as treatment of choice in extrapulmonary undifferentiated small cell carcinomas.
Extrapulmonary undifferentiated small cell carcinomas, especially those arising in the upper aerodigestive tract, form a group of neoplasms with a clinical behavior which resembles small cell carcinoma of the lung. In 11 patients treated by combination chemotherapy an objective response rate of 82% was achieved for a median duration of 8+ months. Median survival for all patients was 12 months. Long-term survival was observed in those patients with limited disease who achieved a complete response after chemotherapy followed by radiotherapy.
Enucleation of tumor versus partial nephrectomy as conservative treatment of renal cell carcinoma.
In patients with renal insufficiency, solitary kidney, or bilateral renal malignancies, conservative surgery for renal cell carcinoma has been suggested. The authors treated 17 such patients with either enucleation of tumor or partial nephrectomy. Overall survival from disease in this series was 58.8%. Seventy percent of patients undergoing enucleation and 42.9% undergoing partial nephrectomy survived with a mean follow-up period of 5 years. Survival or local recurrence rate after enucleative surgery is an effective treatment of renal carcinoma in selected patients, and despite concerns about tumor invasion of the pseudocapsule, the clinical data do not indicate any difference in survival. There was no significant difference between enucleation of tumor and partial nephrectomy regarding morbidity, mortality, or recurrence rate.
Sarcoid reaction mimicking intrathoracic dissemination of testicular cancer.
The close observation of patients treated for testicular cancer led to the suspicion of intrathoracic and/or mediastinal metastases on radiologic examination in a number of patients without other evidence of relapse. This report presents two patients with combined seminomatous and nonseminomatous germ cell tumors with isolated sarcoid reactions of hilar and interlobular lymph nodes, detected concomitant with diagnosis and 12 months after diagnosis, respectively. Histologic examination appears to be imperative in these cases to avoid unnecessary chemotherapy.
The relationship of nasopharyngeal carcinomas and second independent malignancies based on the Radiation Therapy Oncology Group experience.
The authors sought to learn if the incidence of second independent malignancies after the irradiation of carcinomas of the nasopharynx is similar to that observed after treatment of tumors arising in other head and neck sites. One hundred twenty-one patients who had primary carcinomas of the nasopharynx who were treated solely by ionizing radiation (according to the specifications of a Radiation Therapy Oncology Group protocol) were identified and their subsequent well-being was reviewed. Overall there was a 4.1% incidence of second malignancies (2% after 3 years, 5% after 5 years, and 8% after 8 years) with most arising in the upper aerodigestive tract. This rate is significantly less than the rate associated with other head and neck sites. It is not significantly different from the rate of first malignancies observed in an age-matched and sex-matched population. When only those patients who were free of all evidence of neoplastic disease 6 months after the completion of radiotherapy are considered, similar analysis leads to similar outcomes. The authors conclude that the risk of second malignancies after the successful irradiation of carcinomas of the nasopharynx is substantially less than after treatment of tumors at other head and neck sites.
The contribution of routine follow-up mammography to an early detection of asynchronous contralateral breast cancer.
The role of routine mammography was assessed in the early detection of asynchronous contralateral breast cancer (ACBC). The breast cancer patient populations of two cities, Nijmegen and Eindhoven, The Netherlands, which were subjected to a well-defined follow-up program, were compared. The program consisted of regular physical examination and annual mammography in Nijmegen and physical examination only in Eindhoven. From 1975 until 1987, 24 ACBC patients were detected within a group of 880 breast cancer patients in Nijmegen (3%) and, from 1971 until 1984, 14 ACBC patients within a group of 411 patients in Eindhoven (3%). In Nijmegen, eight of the 23 evaluable patients (35%) had a contralateral tumor with a histologic size smaller than 10 mm or an in situ carcinoma, compared with one of the 14 of the Eindhoven patients (7%), whereas 18 of the 24 (75%) versus eight of the 14 patients (57%) were node-negative. Thus annual mammography is very likely a contribution in the early detection of contralateral breast cancer as compared with follow-up by regular physical examination only.
Attributes and survival patterns of multiple primary cutaneous malignant melanoma.
From a series of 1495 patients with primary cutaneous malignant melanoma (PCMM), 26 patients (1.73%) had multiple primary cutaneous malignant melanoma (MPCMM). This report describes the attributes and survival patterns in this small, but important, subgroup of patients with PCMM. Of 26 patients, 23 had two primaries, two had three primaries, and one had six primaries. Five patients had synchronous and 21 patients had metachronous MPCMM. The median interval between the occurrence of the first and subsequent PCMM in these patients was 1.93 years. The estimated 5-year survival rate from the first melanoma was 83.5%; that from the last melanoma was 53.1%. In summary, MPCMM is a distinct biologic phenomenon. A second or subsequent malignant melanoma should be treated like a primary melanoma.
Second cancers following non-Hodgkin's lymphoma.
The risk of second malignancies following non-Hodgkin's lymphoma (NHL) was estimated in 29,153 patients diagnosed with NHL between 1973 and 1987 in one of nine areas participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Compared with the general population, NHL patients were at a significantly increased risk of developing second cancers (observed/expected [O/E] = 1.18; O = 1231). The O/E ratio increased significantly with time to reach 1.77 in 10-year survivors. Significant excesses were noted for acute nonlymphocytic leukemia (O/E = 2.88), cancers of the bladder (O/E = 1.30), kidney (O/E = 1.47), and lung (O/E = 1.57), malignant melanoma (O/E = 2.44), and Hodgkin's disease (O/E = 4.16). Chemotherapy appeared related to subsequent acute nonlymphocytic leukemia (ANLL) and bladder cancer. Radiation therapy was associated with ANLL and possibly cancers of the lung, bladder, and bone. Malignant melanoma was not clearly related to initial NHL treatment.
Interleukin-3. Biologic effects and clinical impact.
Human interleukin-3 (IL-3) is expressed in yeast and has a specific activity of 5 x 10(7) U/mg of protein. It exerts functional and proliferative effects on multiple hematopoietic cell lineages including the neutrophil, eosinophil, basophil, monocytic, and thrombopoietic cell lines. IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) share common binding capacities on hematopoietic cells. Each of these agents has entered clinical trials. The clinical experiences with IL-3 alone and in combination with GM-CSF in a Phase I/II trial are summarized in this report.
Electrical taste detection thresholds and chemical smell detection thresholds in patients with cancer.
Taste sensation in patients with cancer has previously been studied with the cumbersome method of chemical gustometry, which have produced inconsistent results. In this study taste thresholds were determined with the simple and reliable technique of electrogustometry in 51 patients with cancers of the lung (small cell), ovary or breast, and in 29 matched control patients with nonneoplastic disease. Chemical smell thresholds for phenyl-methyl-ethyl-carbinol were studied in the same group of patients. Electrical taste threshold was higher in patients with cancer compared with control patients (30 [12 to 80] microA versus 9.5 [6.1 to 24] microA; median [interquartile range], P less than 0.001). No differences were seen in smell thresholds. Patients who responded to chemotherapy obtained a decreased electrogustometric threshold at time of reevaluation (24 [8 to 64] microA versus 30 [15 to 90] microA; median [interquartile range], P less than 0.05). These results suggest an effect of the malignant disease itself on taste thresholds.
Contribution of in vivo proliferation/differentiation studies toward the development of a combined functional and morphologic system of classification of neoplastic diseases.
Proliferation kinetics of both leukemia and a variety of solid tumors have been assessed after in vivo infusions of the thymidine analogues, iododeoxyuridine (IUdR) and bromodeoxyuridine (BrdU). In acute myeloid leukemia (AML), these data indicate that the pretherapy cell cycle time (Tc) of myeloblasts is a prognostic indicator for remission duration since patients with slowly cycling myeloblasts had more durable remissions. The presence of in vivo differentiation detected from the day 7 biopsy after chemotherapy was also of favorable prognosis as these individuals had statistically significant improvement in their remission duration. The data in solid tumors are not mature enough for determining their clinical significance. Since cell kinetic information is readily available in a prompt fashion using these novel techniques, data can be used to plan therapeutic strategies for patients. This review discusses the state-of-the-art techniques available for cell cycle kinetic studies and the clinical and prognostic utility of data that have been generated thus far.
Trends in patterns of treatment of childhood cancer in Los Angeles County.
To assess the proportion of children with cancer who have been managed by mainstream pediatric cancer programs, population-based cancer incidence data for Los Angeles County (LAC) children (under 20 years of age) for the years 1972 through 1987 were linked with patient records of children registered with the two national cooperative pediatric oncology groups, Children's Cancer Study Group and Pediatric Oncology Group. The proportion of children with cancer who were registered by cooperative groups increased markedly over time: 9% of LAC children younger than 15 years of age who were diagnosed with cancer in 1972 were registered with cooperative groups, compared to 52% of those diagnosed in 1980 and 62% of those diagnosed in 1987. Registration rates decreased with increasing age at cancer diagnosis. In the most recent time period, 1984-1987, 66% of LAC children diagnosed with cancer under age 5 years were registered with cooperative groups compared to 62% of those who were 5 to 9 years old and 49% of those who were 10 to 14 years old; although they were frequently diagnosed with tumors considered to be childhood cancers, only 19% of older adolescents (aged 15-19 years) were registered. In LAC, there was no apparent bias in registration rates with regard to gender or racial-ethnic background. Among patients diagnosed in the period 1984-1987, children in the highest of five socioeconomic status categories were underrepresented among registrants. Registration rates were highest (70% or greater) for patients with acute lymphocytic and acute nonlymphocytic leukemia, medulloblastoma, hepatoblastoma, Wilms tumor, and rhabdomyosarcoma. Fewer than 50% of patients with other brain and central nervous system tumors, retinoblastoma, other soft tissue sarcomas, and bone tumors were registered with the cooperative groups.