Showing papers by "Memorial Sloan Kettering Cancer Center published in 1982"

Preoperative Chemotherapy for Osteogenic Sarcoma: Selection of Postoperative Adjuvant Chemotherapy Based on the Response of the Primary Tumor to Preoperative Chemotherapy

Abstract: Since June 1978, 57 patients with primary osteogenic sarcoma of an extremity were treated with high-dose methotrexate (HDMTX) and citrovorum factor rescue (CFR), Adriamycin, and the combination of bleomycin, cyclophosphamide and dactinomycin (BCD) given for 4-16 weeks prior to definitive surgery. Histologic examination of the resected primary tumor determined the effect of preoperative chemotherapy with many primary tumors showing greater than 90% tumor necrosis attributable to preoperative chemotherapy. All patients having this favorable effect of chemotherapy on the primary tumor were continued on the same chemotherapy regimen postoperatively (regimen B). However, in those patients not having a good effect of preoperative chemotherapy on the primary tumor, HDMTX with CFR was subsequently deleted from their postoperative chemotherapy and they were placed on a regimen containing cisplatinum at the dose of 120mg/M2 with mannitol diuresis combined with Adriamycin in addition to BCD (regimen A). In the current study, 35 of the 57 patients did not demonstrate a good effect of chemotherapy on the primary tumor and were assigned to regimen A postoperatively. Of these 35 patients, 32 (91%) have remained continuously free of recurrent or metastatic disease from 6-34 months following the start of therapy. Among the 22 remaining patients having a good histologic response and treated with regimen B postoperatively, there has been only one relapse in a patient who had a local recurrence in the area of an inadequately resected primary tumor three months after the cessation of chemotherapy. Thus, 53 of 57 patients (93%) are continuously with no evidence of recurrent or metastatic disease from 6-35 months (median, 20 months) from the start of treatment. This study demonstrates the value of thorough histologic examination in predicting survival in responding patients and in helping identify patients whose disease-free survival rate can be substantially increased if they are given alternative postoperative adjuvant chemotherapy after failing to have a good response to preoperative chemotherapy. This individualized chemotherapeutic strategy has yielded the highest disease-free survival rate reported to date for osteogenic sarcoma.

Diagnosis and treatment of leptomeningeal metastases from solid tumors: Experience with 90 patients

Abstract: The clinical findings and response to treatment of leptomeningeal metastases from solid tumors are analyzed in 90 patients treated at Memorial Sloan-Kettering Cancer Center during the period from January 1975 to February 1980. Patients included those who had either typical clinical findings of leptomeningeal tumor or conclusive laboratory evidence supporting the diagnosis. Carcinoma of the breast (46 patients), lung (23 patients) and melanoma (11 patients) were the common primary tumors. Symptoms of leptomeningeal metastasis occurred as the presenting sign in five patients and as late as ten years after the primary tumor was diagnosed in four other patients. Most patients had active systemic disease outside the nervous system. Signs and symptoms could be classified as involving either the brain, cranial nerves, or spinal nerves. Most patients had either symptoms or signs in more than one area at the time the diagnosis was established. The initial spinal fluid examination was abnormal in all but three patients, but only 49 had cytologic evidence of leptomeningeal metastases. Repeated spinal fluid assay yielded a positive cytology in 82 patients. Measurement of biochemical markers, including beta-glucuronidase, carcinoembryonic antigen and lactic dehydrogenase, assisted in the diagnosis. Approximately half of the patients treated by intraventricular methotrexate experienced improvement or stabilization of neurological symptoms for more than a month; median survival was 5.8 months after diagnosis, with a range of 1--29 months. In 18 patients disease was limited to the nervous system, and median survival was eight months, with four patients surviving one year and two patients for two years. Side effects of therapy were, for the most part, minor. We conclude that vigorous treatment of leptomeningeal metastases with intrathecal chemotherapeutic agents improves symptomatology in some patients, and at times prolongs survival.

Peripheral nerve sheath tumors: An electron microscopic study of 43 cases

Abstract: To obtain data concerning their histogenesis, 23 benign solitary schwannomas (including five cellular variants), 10 neurofibromas, and 10 malignant peripheral nerve sheath tumors were studied by electron microscopy. The results confirm previous findings that solitary schwannomas (so-called neurilemomas) are composed principally of cells showing features of differentiated Schwann cells. The principal cells of neurofibromas on the other hand did not resemble differentiated Schwann cells. The predominant cell type in six cases was indistinguishable from normal perineurial cells. Schwann cell-axon complexes seen in three cases may have represented entrapped normal structures or perhaps one component of a hamartomatous tumor. In contrast to the benign neoplasms the cells of the ten malignant peripheral nerve sheath tumors were in general poorly differentiated. When differentiated, they shared some features with Schwann and perineurial cells. Cell forms intermediate between them and fibroblastic cells were also identified. These findings indicate that schwannoma and neurofibroma are distinct entities. In the authors' experience schwannomas rarely undergo malignant change. For this reason and because it is unclear whether malignant tumors of peripheral nerves arise from more than one sheath cell, the designation of malignant peripheral nerve sheath tumor (PNST) is preferable to malignant schwannoma.

Myosarcomas of the stomach: natural history, prognostic factors and management.

Abstract: A retrospective study was made of 41 patients treated for gastric myosarcoma to identify prognostic factors that influence results. The adjusted five- and ten-year survival rates were 56% and 43% respectively, with no significant difference between leiomyosarcoma and malignant leiomyoblastoma. A histopathologic grade of malignancy could be assigned to each tumor according to the degree of hypercellularity, nuclear abnormality, mitotic rate and other characteristics. High histopathologic grade, large tumor size (greater than 5 cm diameter) and invasion of adjacent organs adversely affected prognosis. Five-year survival after curative treatment was: 100% (9/9) for small tumors, of which six were treated by wedge gastric resection; 67% (8/12) for large tumors, mostly after subtotal gastrectomy; and 0% for tumors that invaded adjacent organs, despite extended resections. It is concluded that the management of gastric myosarcomas can be planned according to these prognostic factors and that multimodal therapy of tumors with adverse factors warrants consideration.

Primary gastrointestinal lymphoma: A 30‐year review

Abstract: The authors reviewed all cases of non-Hodgkin's lymphoma primarily involving the gastrointestinal tract treated at Memorial Hospital during the period from 1949-1978. Complete clinical records were available in 104 cases. Slides of original pathology specimens were available in 81 cases. Tumors were classified by Rappaport, Lukes-Collins and modified Kiel classifications. All patients were staged retrospectively, using modified Ann Arbor staging. The primary tumor was in the stomach in 76 patients, in the small bowel in 15 and in the large bowel in 13. The life-table survival for all patients at five years was 44% and for the 81 Stage I and II patients it was 53%. We found a trend toward improved survival for patients treated in the last decade (P = 0.05). Using Cox regression analysis, survival was found to be correlated with stage (P less than 0.0001) and involvement of adjacent structures (P = 0.007). For Stage I patients, resection and radiation therapy were equally effective alone in controlling local tumor even though factors responsible for the selection of either treatment could not be identified. For Stage II patients, resection combined with radiation therapy controlled local disease better than either treatment alone. For Stage II, patient survival was correlated with the pattern of nodal involvement (P less than 0.0001). Neither the choice of treatment (resection, radiation therapy, or resection with radiation therapy; P = 0.17) nor the involvement of resected margins (P = 0.22) affects survival. Among 81 Stage I and II patients, 68% had recurrences outside the primary field of treatment and 60% outside the abdomen. Systemic multiple modality therapy should be considered for patients at high risk for recurrence.

Malignant mesothelioma of the pleura: review of 123 patients.

Abstract: One-hundred-twenty-three cases of malignant pleural mesothelioma were reviewed Exposure to asbestos or to other industrial dusts or chemicals was an important etiologic factor with 24% of patients relating such a history A history of prior irradiation or previous lung disease was also occasionally noted Diagnosis was most often made by exploratory thoracotomy, with pleural biopsy or cytology rarely helpful Except for nine patients, tumor was confined to the chest at the time of diagnosis, but in 33 of the remaining 114 patients, spread to the abdomen or distant metastasis was seen during the course of disease Surgery and radiotherapy were ineffective in preventing local recurrence There were only three major responses to chemotherapy in 111 trials Median survival was 12 months, and only seven patients (56%) lived more than five years Patients with epithelial mesothelioma and Stage I disease had the most favorable prognosis

Autopsy findings in 154 patients with germ cell tumors of the testis

Abstract: Autopsy findings are reviewed in 154 patients treated for germ cell tumors of the testis Of the patients with apparently pure seminoma, 44% had autopsy evidence of nonseminomatous metastases For all tumor types, the most common sites of distant metastasis were lung (89%), liver (73%), brain (31%), and bone (30%) There was a high incidence of brain metastases in choriocarcinoma and of bone metastases in seminoma Brain, liver, and bone metastases were late occurrences in the course of the disease and were almost always associated with involvement of other sites Recurrences in the retroperitoneal area after lymph node dissection occurred mainly in those who had had retroperitoneal lymph node metastases No difference in site or frequency of metastases was apparent in autopsied patients treated before or after introduction of platinum containing regimens Respiratory failure, secondary to lung metastases, was the most common cause of death Of the autopsied patients, 6% died of iatrogenic causes

Late-onset steroid 21-hydroxylase deficiency: a variant of classical congenital adrenal hyperplasia.

Abstract: Hormonal studies and human leukocyte antigen (HLA) genotyping were performed in 5 males and 13 females who were demonstrated to have 21-hydroxylase deficiency. The enzymatic deficiency of steroidogenesis was detected by family studies of 10 females who presented with varying symptoms of androgen excess. The 10 index cases had normal genitalia at birth, but virilized to varying degrees postnatally. The additional 8 affected family members had not sought medical care, but some were found to have signs of virilization on physical examination, while others were normal. Thus both late-onset (symptomatic) and cryptic (asymptomatic) 21-hydroxylase deficiency occurred in the same pedigree. The hormonal and genetic linkage studies indicate that the late-onset (symptomatic) form of 21- hydroxylase deficiency, like the cryptic (asymptomatic) and classical forms of 21-hydroxylase deficiency, is transmitted by an autosomal recessive gene which is linked to HLA-B. Furthermore, the classical form of 21-hydroxylase defic...

Carcinoma of the colon and rectum: The natural history reviewed in 1704 patients

Abstract: For 1704 patients with large bowel cancer compiled by the Armed Forces Central Medical Registry, selected prognostic factors were related to five-year or longer survival. The majority of late deaths (those occurring after five years) resulted from cancer in the descending colon, sigmoid colon or rectum rather than from cancer in the right or transverse colon. For example, among all patients with cancer of the rectum, 15.4% of those with Dukes' B tumors and 10.9% of those with Dukes' C tumors died of rectal cancer between five and ten years after diagnosis. When late survival rates were compared, patients with right and transverse colon cancer (8 deaths/93 at risk) fared significantly better than those with left colon and rectal cancer (33 deaths/171 at risk; P = 0.01). Among patients with left-sided colon and rectal carcinoma, a further significant difference in late survival was found when stage of disease was considered: patients with Dukes' A cancers (3 deaths/47 at risk after five years) fared better than those with Dukes' C cancers (21 deaths/74 at risk) (P = 0.002). For Dukes' B and C stages of disease, patients with left colon and rectal cancer fared worse than those with right and transverse colon lesions after 60 months. Of all patients who died of large bowel cancer after five years, 69% had a recurrence of cancer by 60 months, and most late recurrences were located in the descending and sigmoid colon and in the rectum. These results show differences in survival after five years with respect to both site of cancer in the colon and stage of initial disease. Our findings indicate that many left-sided large bowel cancers have a slowly progressive natural history.

A randomized trial of ascorbic acid in polyposis coli.

Abstract: The possibility of pharmacological control of large bowel adenomas has been suggested by effectiveness of antioxidants in experimental tumor models and by the results of a limited clinical study using ascorbic acid. Over a two year period we tested this hypothesis in a randomized, double-blind study of 49 patients with polyposis coli. Of 36 patients who were evaluable at completion, 19 had received ascorbic acid, 3 g/day, and 17 had received a placebo. We found a reduction in polyp area in the ascorbic acid-treated group at nine months of follow-up (P less than 0.03) and trends toward reduction in both number and area of rectal polyps during the middle of the trial. A labeling study of rectal epithelium with tritiated thymidine also hinted at a treatment effect. Our data suggest that ascorbic acid temporarily influenced polyp growth or turnover. Although these results have no current therapeutic value, our findings support continued studies of chemoprevention in this and other high risk settings.

Combination hyperthermia and radiation therapy for malignant melanoma

Abstract: Since 1975, clinical studies have been carried out to determine whether radiation when combined with localized hyperthermia evokes improved tumor control compared to that achieved with radiation alone. Local tumor hyperthermia was achieved using radiofrequency inductive heating at 27.12 MHz. In bulky lesions (>100 cm/sup 3/), radiofrequency conductive heating at 13.56 MHz was also used. More than 100 lesions in 38 patients were treated with radiation alone and hyperthermia in combination with radiation. Most lesions were treated either twice a week or once a week, depending on radiation dose fractionation scheme used. The overall result of tumor control rate of the combined therapy is superior to radiation therapy alone (75% versus 46%; P < 0.01). No enhanced normal tissue morbidity was seen following the combined therapy. The detailed analysis of the treatment results shows that the tumor control rate is dependent on dose per fraction, the total dose, and the initial tumor volume. The radiation alone, at high doses per fraction, was effective in controlling 80% of the lesions, if the tumor volume was less than 10 cm/sup 3/, compared to 30% when the tumor volumes were larger. The combination therapy, on the other hand effected 80% local tumor controlmore » regardless of the tumor volume. The importance of good thermal distribution within the tumor volume, selective heating of the tumor tissues and the sequence and time interval between the combined therapy is discussed.« less

Group B erythrocytes enzymatically converted to group O survive normally in A, B, and O individuals

Abstract: With an alpha-galactosidase, B erythrocytes can be converted to blood group O under conditions that neither impair their viability in vitro nor affect their ability to survive normally after transfusion to individuals of groups O, A, and B. Such an approach has the potential for producing enzymatically converted group O cells for use in transfusion therapy. It should also be possible to convert A cells to group O by using the appropriate alpha-N-acetylgalactosaminidase.

Cell heterogeneity during the cell cycle

Abstract: Using flow cytometry, populations of Chinese hamster ovary cells, asynchronous and synchronized in the cycle, were measured with respect to cellular RNA- and protein-content, as well as cell light scatter properties. Heterogeneities of cell populations were expressed as coefficients of variation (c.v.) in percent of the respective mean values. Populations of cells immediately after mitosis have about 15% higher c.v. than mitotic cell populations, regardless of whether RNA, proteins, or light scatter are measured. These data indicate that cytoplasmic constituents are unequally distributed into the daughter cells during cytokinesis and that unequal cytokinesis generates intercellular metabolic variability during the cycle. An additional increase in heterogeneity, although of smaller degree, occurs during G/sub 2/ phase. Populations of S-phase cells are the most uniform, having 20-30% lower c.v. than the postmitotic cells. Cell progression through S does not involve any significant increase in intercellular variability with respect to RNA or protein content. In unperturbed exponentially growing cultures a critical RNA content is required for G/sub 1/ cells prior to their entrance into S. The cell residence times in the equalization compartments are exponentially distributed, which may reflect the randomness generated by the uneven division of metabolic constituents to daughter cells during cytokinesis.more » The cell heterogeneities were presently estimated at two metabolic levels, transcription (RNA content) and translation (proteins). The most uniform were populations stained for RNA and the highest variability was observed after staining of proteins. This suggests that the regulatory mechanisms equalizing cells in the cell cycle may operate primarily at the level of DNA transcription.« less

Recovery from aspermia induced by low-dose radiation in seminoma patients

Abstract: Gonadal dosimetry and spermatogenic activity was monitored in patients given radiation therapy (RT) after unilateral orchiectomy for seminoma. The RT given was, with minor variations, 3200 rad in 16 fractions in four weeks to the para-aortic and ipsilateral pelvic inguinal lymphatics in order to include the orchiectomy scar. The incidental amount of radiation to the remaining testicle averaged 78.4 +/- 7.4 rad and ranged from 32-178 rad as determined by thermoluminescent dosimetry. Induction of aspermia was documented in ten out of 14 patients who received over 65 rad to the gonad. At lower doses, aspermia may not have occurred or was of short duration. Recovery of sperm in the semen occurred in 12 patients within 30-80 weeks after start of treatment. The data suggest that the time of recovery may be dose dependent within the range of 19-148 rad. During the period of recovery, patients with oligospermic semen may be fertile and should be so advised.

Cloning and screening of sequences expressed in a mouse colon tumor.

Abstract: Polyadenylic acid-containing cytoplasmic RNA was isolated from a dimethylhydrazine-induced mouse transplantable colon carcinoma. Double-stranded complementary DNA synthesized using these molecules was inserted into the HindIII site of pBR322 using HindIII linkers, and the recombinant molecules were cloned in Escherichia coli. Clones were screened with labeled complementary DNA synthesized from the polyadenylic acid-containing cytoplasmic RNA of the tumor or normal mouse colon, liver, or kidney. Of 378 clones screened with the normal colon and tumor probes, seven showed major increases in abundance in the tumor tissue as compared to normal, and one showed a major decrease. Twenty-five other sequences were found which showed smaller increases and 22 showed smaller decreases. Of 373 clones screened with tumor, colon, liver, and kidney probes, 79% exhibited little evidence of tissue specificity in expression. The data for those sequences which do show tissue-specific regulation of expression suggest that the tumor continues to express sequences characteristic of the colon but also shows a loss, or decrease, in other gene products, most of which (19 of 25) are characteristic of the colon. Finally, nine of 10 sequences which increase from low abundance in the normal colon to high abundance in the tumor are found at a moderate to high level in the liver and kidney. On the other hand, 23 of 36 sequences which show more modest increases in the tumor as compared to normal are scarce or absent in the liver and kidney.

Treatment of neuroectodermal brain tumors

Abstract: Prospective clinical trials support the view that malignant neuroectodermal tumors should be treated vigorously using a multimodal approach that includes surgical resection, high-dose radiation therapy, and prolonged maintenance chemotherapy. Less malignant astrocytomas and oligodendrogliomas should be treated by resection and irradiation. Laboratory research on neuroectodermal tumors has advanced rapidly, providing new data on tumor cell biology and the pharmacology of chemotherapy that directly influence the therapeutic options.

A comparison of mathematical methods for the analysis of DNA histograms obtained by flow cytometry

Abstract: . Twelve methods for analysing FCM-histograms were compared using the same set of data. Some of the histograms that were analysed were simulated by computer and some were taken from experiments. Simulated data were generated assuming asynchronously growing cell populations and (i) measurement coefficients of variation (CV) from 2 to 16%; (ii) constant measurement CV or CV's increasing from G1 to G2 phase, and (iii) varying fractions of cells in each phase. Simulated data were also generated assuming synchronous cell populations in which a block in early S phase was applied and released. DNA histograms were measured for L-929 cells at various times after mitotic selection. Labelling indices were also measured for these cells at the same time. The fractions of cells in the G1, S, and (G2+ M) phases were calculated by each analytical method and compared with the actual fractions used for simulation, or in case of experimental data, with autoradiographic results. Generally, all methods yielded reasonably accurate fractions of cells in each phase with relative errors in the range of 10–20%. However, most methods tended to overestimate G1 fractions and underestimate S fractions. In addition, variations in the shape of the S phase distribution often caused considerable errors. Phase fractions were also calculated for histograms of kinetically perturbed populations, simulated as well as experimental The errors were only slightly larger than for histograms from asynchronously growing cell populations.

Metastatic melanoma of unknown primary

Abstract: A retrospective study of 166 patients with metastatic melanoma of unknown primary was performed. These were selected from 3805 cases of melanoma in Memorial Sloan-Kettering Cancer Center from 1949 through 1975 (an incidence of 4.4%). There were 109 male and 57 female patients, 75 with Stage II disease and 91 with Stage III. The site of predominant involvement in Stage II patients was the axilla (47%). Five- and ten year survival rates of Stage II patients were 46% and 41%, respectively. The only factor that was shown to influence their survival was the delay (three months or more) of radical lymphadenectomy after initial histologic diagnosis. As expected, the prognosis of Stage III patients was very poor. Our study showed that patients with metastatic melanoma of unknown primary followed a similar clinical course as the Stages II and III patients with overt primary lesion. Stage II patients could expect a reasonable survival, the treatment of choice being prompt radical regional lymphadenectomy.

Significance of the labeling index and labeling distribution as kinetic parameters in colorectal mucosa of cancer patients and DMH treated animals

Abstract: To shed light on the more elevated labeling index (LI) found in the normal appearing mucosa of a group of colon cancer patients previously reported by Maskens and Deschner, the same data together with that from patients with an isolated adenoma, DMH treated CF1 mice and BD IX rats were analyzed on the basis of individual crypt values. One of 13 control patients had crypt values over 15% in contrast to 17 of the 26 cancer and polyp patients (P 15% revealed the Stage I defect in addition to an upward shift in the major zone of DNA synthesis from the lower to the middle and upper thirds of glands (Stage II abnormality), although both abnormalities were more emphatically expressed in glands with a high LI. Individual crypts in DMH treated mice had LI far higher than controls whereas no real differences in crypt LI were found between DMH treated rats and controls. Similar to colon cancer patients, both categories of crypts in DMH treated mice had the Stage I and II proliferative defects. Crypts in DMH treated rats, however, showed a downward shift of the major zone of DNA synthesis from the middle and upper third of glands. That DMH induces primarily microinvasive carcinomas in rats while in mice predominantly adenomas form, a proportion of which becomes malignant, would suggest a relationship between the direction of the shift of the major zone of proliferation and the type lesion induced. In man and mouse, hyperactive crypts would have a selective advantage over other glands allowing earlier expression of neoplastic transformation within them. Furthermore, their recognition as a marker along with the Stage II defect may be useful in tissues at high risk for colorectal tumorigenesis.

Detection and follow‐up of carcinoma of the urinary bladder by flow cytometry

Abstract: Automated flow cytometry (FCM) has been used to study saline bladder irrigation specimens from nearly 400 patients at Memorial Sloan-Kettering Cancer Center during the two-year period March 1979–March 1981. These include 36 patients with papilloma, 35 with noninvasive papillary transitional cell carcinoma, 71 with flat carcinoma in situ, and 52 with invasive carcinoma of the bladder, as well as 110 well patients with a history of low-stage bladder tumors (98 had two or more examinations) and 100 patients without neoplastic disease of the bladder. The false-positive rate for patients with normal bladders or non-neoplastic bladder diseases was 2% (two patients); both had severe cystitis and bladder calculi. The false-negative rate for the group with histologically proven tumors was 18%; excluding papilloma it was 7%. A FCM diagnosis of bladder tumor antedated the development of cystoscopically visible tumor by up to 12 months in 18 patients. Fourteen additional patients have positive FCM at present with or without positive conventional cytology and continue to be followed. These data suggest that FCM can provide an objective quantitative measure of the exfoliated epithelial cells in bladder irrigation specimens, and is at least as sensitive and specific as conventional urine cytology for the detection of cancer cells. An interpretation of each specimen is recorded on a computer-generated hard copy replica of the two-dimensional scattergrams, or pseudo-three-dimensionl projection of the data and used by the clinician as a permanent report of that specimen. FCM has a practical application in the detection and diagnosis of bladder carcinoma among subjects at high risk, and is of value in monitoring the course of this disease and anticipating recurrence following conservative treatment.

Telangiectatic osteogenic sarcoma: a clinicopathologic study of 124 patients.

Abstract: One hundred-twenty-four patients with this rare and special variant of osteogenic sarcoma were treated at Memorial Sloan-Kettering Cancer Center from 1921 through 1979, representing 11% of all of osteogenic sarcomas. The lesions were predominantly lytic, destructive tumors with only minimal sclerosis on roentgenograms and soft as well as cystic on gross examination. Histologically, aneurysmally dilated spaces lined or traversed by sarcoma cells producing osteoid were noted. The differential diagnosis both radiographically and histologically included several benign lesions like aneurysmal bone cyst and giant cell tumor, among many others. It was found that telangiectatic osteogenic sarcoma is relatively frequent in the femoral diaphysis and in the distal end of the femur. Twenty-nine percent of the patients present with pathologic fracture, or this develops later. Age and sex distribution, or clinical signs or symptoms were those of ordinary osteogenic sarcomas. No differences in survival rates were found in lesions that were purely lytic or those with minimal sclerosis. Similarly, no differences in survival were noted when comparing patients with telangiectatic or ordinary osteogenic sarcoma. As a matter of fact, definite increase in survival was found in patients treated since 1975 with preoperative multidrug chemotherapy employing high-dose methotrexate. Adriamycin, and the combination of bleomycin, cyclophosphamide, and dactinomycin.