Showing papers by "Memorial Sloan Kettering Cancer Center published in 1979"

Primary osteogenic sarcoma: the rationale for preoperative chemotherapy and delayed surgery.

Abstract: From 1973--1975, 31 patients with biopsied primary osteogenic sarcoma were treated with preoperative chemotherapy followed by surgical ablation of the primary tumor. Surgery was delayed in order to obtain a custom-fitted prosthetic bone implant in an attempt to avoid amputation. Preoperative chemotherapy included high dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) and adriamycin (T-5 protocol) and was administered for 3 months preoperatively and continued with the inclusion of cyclophosphamide for approximately 5 months postoperatively. At a follow-up period of 30--52 months, 23 of 31 patients (75%) are surviving (21 of 23 with no evidence of disease). Histologic examination of primary tumor removed at surgery revealed varying degrees of tumor destruction (from very little effect to no evidence of viable tumor) attributable to the effect of chemotherapy. The 21 patients that are disease-free survivors had a more complete effect of preoperative chemotherapy on the primary tumor. Some patients achieving favorable effects upon the primary tumor did so only after the dose of HDMTX was escalated to greater than the starting dose of 8 g/m2. Preoperative chemotherapy for all patients with osteogenic sarcoma would seem to offer the following advantages: 1) Evaluation of the effect of HDMTX with CFR on the primary tumor with escalation of the dose of HDMTX until a clinical response is observed, thus defining the dose of HDMTX effective in that patient, to be continued postoperatively as adjuvant therapy; 2) The early use of systemic therapy to eradicate distant microfoci of disease that will eventually kill the patient if not adequately treated by effective chemotherapy; 3) Allow more time for postoperative healing without the need to start adjuvant chemotherapy immediately; and 4) Provide the surgeon time to plan resection surgery. To date, 20 additional patients with biopsy proven osteogenic sarcoma have been treated with more aggressive preoperative chemotherapy (T-7) for approximately 2 1/2 months prior to definitive surgery (resection or amputation). Doses of HDMTX were escalated where necessary and good clinical responses were obtained in 19 of 20 patients. In the majority of patients, no evidence of viable tumor was found on histologic examination of the surgically removed primary tumor. All 20 patients are surviving free of active disease at this brief follow-up period of 4--20 months.

Impairment of cell-mediated immunity functions by dietary zinc deficiency in mice

Abstract: Several immunologic features were analyzed in mice on a zinc-deficient diet [Zn(-)], in mice pair-fed a diet containing zinc [Zn(+)], in mice fed a Zn(+) diet ad lib, and in mice fed laboratory chow ad lib. When placed on a Zn(-) diet, 6- to 8-week-old A/Jax, C57BL/Ks, and CBA/H mice showed loss of body weight, low lymphoid tissue weight, and profound involution of the thymus within 4-8 weeks after initiation of the regimen. Approximately 50% of the mice on the Zn(-) diet developed severe acrodermatitis enteropathica (lesions on tail and paws) and diarrhea. Pair-fed mice on the Zn(+) diet did not show any of these symptoms. Mice on the Zn(-) diet showed the following immune deficiencies: (i) depressed plaque-forming cells against sheep erythrocytes after in vivo immunization; (ii) depressed T killer cell activity against EL-4 tumor cells after in vivo immunization; and (iii) low natural killer cell activity. However, antibody-dependent cell-mediated cytotoxicity against chicken erythrocytes was normal in the mice on the Zn(-) diet. Deficiency of T killer cell activity was not observed when immunization with EL-4 allogeneic lymphoma cells was carried out in vitro. Progressive loss of relative and absolute number of Thy 1.2+ cells and a proportionate relative increase in cells bearing Fc receptors was seen in spleen and lymph nodes of Zn(-) animals. It appears that zinc is an essential element for maintenance of normal T cell and other immune functions in vivo.

Regulation of macrophage and granulocyte proliferation. Specificities of prostaglandin E and lactoferrin

Abstract: Hemopoietic colony-forming cells committed to macrophage differentiation (M-CFC) are selectively and differentially inhibited by prostaglandin E (PGE). A hierarchy of sensitivity was observed among murine CFC stimulated by colony-stimulating factors (CSF) which differ in their ability to initiate proliferation of morphologically distinct colony types, or stimulated by CSF provided by macrophage feeder layers. Inhibition of macrophage colony formation to 50 percent levels occurred with PGE concentrations between 10(-8) and 10(-9) M, and was still evident at 10(-10) -10(-11) M PGE concentrations. The growth of mixed colonies containing both macrophages and neutrophils was less sensitive to the inhibitory effects of PGE, however, the monocytoid component of these colonies was reduced in the presence of PGE. Neutrophil progenitor cell proliferation was not influenced by PGE concentrations below 10(-6) M, regardless of time of addition of PGE, whereas clonal macrophage expansion, as well as clone size, was sensitive to inhibition by PGE when added as late as 3 d after culture initiation. Prostaglandin F(2α), was not inhibitory to colony formation. Experimental evidence for a selective role of macrophage PGE in the regulation of macrophage colony formation was directly provided by utilizing resident peritoneal macrophages as a source of CSF for bone marrow target cell overlays. Simultaneous morphological analysis of colonies proliferating in bilayer culture in response to increasing concentrations of macrophages, and direct measurements of PGE synthesized by an identical number of macrophages maintained in liquid culture demonstrate that a specific decline in macrophage colony formation occurs coincident with a linear increase in macrophage PGE synthesis. Inhibition of macrophage PGE synthesis by indomethacin results in the specific enhancement of macrophage colony formation. Furthermore, macrophage PGE synthesis is induced by CSF preparations with the selective capacity to differentially stimulate macrophage proliferation, but not by those which preferentially stimulate granulocyte colony formation. In comparison to the effects of PGE on M-CFC, polymorphonuclear granulocyte-derived lactoferrin (LF) reduces macrophage production of colony-stimulating activities for macrophage, mixed macrophage- neutrophil and neutrophil colony formation. The ability of LF to reduce macrophage PGE synthesis, presumably by decreasing CSF production, suggests that LF and PGE can interact in the control of macrophage and granulocyte proliferation.

Induction of prostaglandin E synthesis in normal and neoplastic macrophages: Role for colony-stimulating factor(s) distinct from effects on myeloid progenitor cell proliferation

Abstract: The biosynthesis of prostaglandin E (PGE) by normal and neoplastic macrophages is intrinsically linked to their synthesis of, and exposure to, myeloid colony-stimulating factors (CS-factors). The defect in responsiveness to endotoxin lipopolysaccharide (LPS) by macrophages from C3H/HeJ mice extends equally to the synthesis of CS-factor and PGE. However, C3H/HeJ macrophages can be stimulated to synthesize PGE by treatment with agents other than LPS [zymosan, tuberculin purified protein derivative, concanavalin A, poly(I).poly(C)], which also stimulate CS-factor production, or by the addition of various preparations of soluble CS-factor. In peritoneal wash preparations, constitutive PGE synthesis occurred in rapidly sedimenting macrophage cells, whereas constitutive CS-factor production and inducible PGE synthesis occurred in slower sedimenting adherent cells. A similar functional heterogeneity in CS-factor and PGE production was found in neoplastic macrophagae cell lines. The association of elevated CS-factor levels and PGE synthesis by macrophages suggests a role for CS-factor in many of the physiological responses heretofore associated with elevated tissue levels of the E type prostaglandins.

Candidiasis: detection by gas-liquid chromatography of D-arabinitol, a fungal metabolite, in human serum

Abstract: D-Arabinitol was identified as a major metabolite of Candida species in human subjects. Gas-liquid chromatography was used to measure the concentration of D-arabinitol in serum. The study included subjects who were healthy and cancer patients who had proven invasive candidiasis or were colonized with Candida. D-Arabinitol concentrations greater than 1.0 microgram per milliliter were found in serum from patients with invasive infection. This technique may prove valuable in the diagnosis of invasive candidiasis.

Subacute motor neuronopathy: a remote effect of lymphoma.

Abstract: Ten patients developed a subacute lower motor neuron syndrome as a remote effect of Hodgkin's disease or other lymphoma. The illness usually followed a benign course independent of the activity of the underlying neoplasm. Seven of the patients improved spontaneously, and 3 became neurologically normal. Two patients died of intercurrent infections related to immunosuppression. Neuropathological examination of these 2 patients and 3 previously reported cases showed prominent neuronal degeneration restricted to the anterior horns of the spinal cord and mild posterior column demyelination. Demyelination was also present in the anterior roots of our autopsied patients and was accompanied by large, hyperchromatic Schwann cells. The cause of the illness is obscure, but both radiation therapy and opportunistic infection may be contributing factors. Attempts at virus isolation have been unsuccessful. The syndrome should be distinguished from the more common direct effects of lymphoma on the nervous system, since its identification spares the patient additional, potentially harmful therapy.

Qat-4 and Qat-5, new murine T-cell antigens governed by the Tla region and identified by monoclonal antibodies.

Abstract: Two new lymphocyte antigens, provisionally designated Qat-4 and Qat-5 have been identified with two different hybridoma-derived, monoclonal AKR antiC57BL/6 antibodies. These antigens are governed by genes located to the right (distal) end of the H-2 complex, within the Qa-2,3 region. Qat-4 and Qat-5 antigens which do not seem to be identical with Qa-2,3 or TL antigens are absent from Ig/ lymphocytes and thymocytes. They are only present on a fraction of peripheral T cells. Thus, Qat-4 is expressed on 70%, and Qat-5 on 30% of splenic and lymph node T cells, Qat-4 is also found on the majority of Ig- cells from athymic nude mice. These findings illustrate the complexity of the chromosome segment between the H-2D and Tla loci and they emphasize the role of major histocompatibility complex-associated genes for the differentiation of T cells into different subpopulations with possibly distinct immunologic functions.

Correlation between cell cycle duration and RNA content.

Abstract: The metachromatic fluorochrome acridine orange was used to differentially stain DNA and RNA in Chinese hamster ovary (CHO) cells and in mitogen-stimulated human lymphocytes during their progression through the cell cycle. Green and red fluorescence of individual cells, representing cellular DNA and RNA, respectively, was measured by flow cytometry. CHO cells were synchronized by selective detachment at mitosis. Their rate of progression through G1 and subsequently through S phase correlated with the content of stainable RNA. The mean duration of the G1 phase was 5.2 hours for cells with high RNA content (highest 25 percentile population) and 8.1 hours for cells with low RNA (lowest 25 percentile). The duration of S phase was 5.9 and 7.5 hours for high- and low-RNA, 25 percentile subpopulations, respectively. Lymphocytes synchronized at the G1/S boundary by hydroxyurea or 5-fluorodeoxyuridine showed extremely high intecellular variation with respect to content of stainable RNA. After release from the block they traversed S phase at rates linearly proportional to the content of stainable RNA. The duration of S phase was five hours for cells with high RNA-, six to nine hours for cells with moderate RNA- and up to 27 hours for cells with minimal RNA-content. The data suggest that the rate of progression the cell cycle of individual cells within a population may be correlated with the number of ribosomes per cell.

Alcohol as a co-factor in the etiology of cancer.

Abstract: Alcohol and tobacco appear to act synergistically in the pathogenesis of epithelial cancers of the oropharynx (excluding lip), larynx, and esophagus. For the subsites within the upper aerodigestive tract, over 10,000 deaths in United States men during 1978 may be attributed to tobacco and alcohol consumption. The cancer sites for which tobacco and alcohol are major determinants occur with greater frequency in men, blacks, lower socioeconomic groups, and with increasing urbanization and increasing age (35--70 years). Because primary hepatocellular carcinoma occurs more commonly in patients with cirrhosis, chronic alcohol abuse is an important risk mechanism for carcinoma of the liver parenchyma. Although experimental animal studies have failed to demonstrate whether ethanol can independently initiate tumorigenesis, various alternative or associated biochemical and immunological mechanisms of action have been proposed.

A survey of psychotropic drug prescriptions in an oncology population.

Abstract: The present study examined the prescription practices concerning psychotropic drugs in 5 major oncology centers over a 6 month period. During the survey period 1579 patients were admitted to the collaborating institutions, and 51% of them were prescribed at least one psychotropic medication. Hypnotics were the most frequently prescribed drugs, accounting for 48% of total prescriptions, followed by anti-psychotics at 26% and anti-anxiety agents at 25%. Anti-depressant drugs accounted for only 1% of psychotropic prescriptions. Analysis of prescription rationales revealed that 44% of the psychotropic prescriptions were written for sleep, while 25% were given for nausea and vomiting; approximately 17% were attributed to psychological distress, and 12% were associated with diagnostic medical procedures. The overall rate of prescription was approximately 2 psychotropic drugs per patient per admission, with only 2% of prescriptions resulting in chart-documented side effects. At the level of individual compounds, 3 distinct drugs accounted for 72% of total prescriptions--flurazepam (33%), prochlorperazine (21%), and diazepam (17%).

Natural Killing of Herpes Simplex Virus Type 1-Infected Target Cells: Normal Human Responses and Influence of Antiviral Antibody

Abstract: Studies of a mouse model of genetic resistance to herpes simplex virus type 1 (HSV-1) indicate that the marrow-dependent effector cell of allogeneic resistance plays an important role in natural resistance to this virus infection. Since the marrow-dependent effector cell appears to be closely related to the natural killer (NK) cells, an NK assay with HSV-1-infected fibroblasts [NK(HSV-1)] has been developed to study this resistance mechanism in humans. Incubation of effector and target cells for 12 to 14 h gave the greatest percent specific release (%SR) and kept spontaneous (51)Cr release from infected target cells below 35%. Patients with Bruton's agammaglobulinemia demonstrated significant kill indicating antiviral antibody was not necessary. Seropositive individuals gave a 9% greater%SR than seronegative individuals. Depletion of B-cells consistently diminished NK (HSV-1) for seropositive individuals and augmented kill for seronegative individuals. Although antiviral antibody produced in culture may contribute to NK (HSV-1), depletion of B-cells allowed quantitation of NK (HSV-1) to the exclusion of most of the antibody-dependent kill. The NK cells detected by this assay showed many of the properties reported for NK cells with K562 targets. Two patients with severe herpesvirus infections demonstrated NK (HSV-1) responses greater than 2 standard deviations below the normal mean. Since normal individuals with virus infections have higher rather than lower natural kill, the low NK (HSV-1) may reflect their susceptibility to the virus infection.

Resected pulmonary metastases from colorectal cancer.

Abstract: A review of 35 patients who, over an 18-year period, underwent excision of pulmonary metastases from colorectal cancer, is presented. The cumulative five-year survival rate was 22 per cent, and this was significantly increased where the primary colonic cancer was Dukes' A or B. No difference in survival was found regarding the disease-free interval and the number of metastatic lesions. The follow-up of patients with colorectal cancer should always include yearly chest x-rays; and when metastases developed in the lungs alone, surgery for their removal is recommended.

Non-Hodgkin's lymphoma in children: a progress report on the original patients treated with the LSA2-L2 protocol.

Abstract: This report is a follow-up of the initial group of 39 children with non-Hodgkin's lymphoma treated with the LSA2-L2 protocol as previously reported in Cancer (37:123--134, 1976). The disease-free actuarial survival is 73%. All surviving patients are off therapy and have shown no evidence of recurrence with a median observation time of 70+ months. Their survival times range from 56+ to 88+ months from diagnosis. An analysis of successes and failures is discussed and modifications in the role of radiation therapy and surgery in the multidisciplinary management of children with non-Hodgkin's lymphoma are advocated. The results in the present series indicate that the LSA2-L2 protocol has substantially improved the prognosis for children with non-Hodgkin's lymphoma. We have concluded that age, sex, primary site (perhaps with the exception of primary skeletal), and histology are not of prognostic significance. The amount of bulky widespread disease at initial presentation, early and aggressive therapy, and the achievement of a complete remission status within 1--2 months from onset of therapy are the most important prognostic factors.

Further description of theLy-5 system

Abstract: TheLy-5 system of alloantigens was reevaluated with the aid of an Ly-5 congenic mouse strain and an additional serological technique, the PA-SRBC rosette assay, not previously applied to Ly-5. In the PA-SRBC assay, SRBC to which PA (Staphylococcal Protein A) has been coupled react with antibodycoated cells to form rosettes. The PA-SRBC assay was more sensitive than the cytotoxicity assay in detecting Ly-5 on all cell types tested, with the exception of thymocytes, on which Ly-5 was more efficiently demonstrable by the latter test. Thus, the use of both assays gave a more complete picture of theLy-5 system. Evidently Ly-5 is expressed on most cells of the hematopoietic lineage, but on no other cells so far tested. The Ly-5+ cell population includes all known sets of T cells, prothymocytes, sets of B cells, cells of myeloid and monocyte-macrophage types and natural killer cells. Erythrocytes and proerythroblasts are Ly-5−, but the Ly-5 phenotype of less differentiated erythrocytic cells is uncertain. By means of radiation chimeras, made by restoring lethally irradiated mice with Ly-5 congenic bone marrow, the weakly Ly-5+ phenotype of liver and of kidney was shown to be due to immigrant circulating cells. The Ly-5 phenotypes of tumors conform to this scheme of Ly-5 tissue representation. The Ly-5+ tumors included more than 40 leukemias tested, plasmacytomas, putative transformed equivalents of slg−: Lyb-2+ early B cells, a mastocytoma, a monocytic line, and three lines related to the macrophage. The other tumors tested -a sarcoma, a spontaneous mammary carcinoma, a teratocarcinoma and a neuroblastoma — were Ly-5−.

A report of the workshops on the current status of the histologic grading of prostate cancer.

Abstract: A national multidisciplinary study of four major systems for the histological grading of primary prostatic cancer was completed during 1978. In a series of workshops culminating in a final review, criteria of grading were critically assessed against the background of patient survival data. The overall consensus was that the Gleason system should tentatively be adopted as the pathologic reference point for classifying patients. This system can be used in conjunction with other systems. It seems definable, reproducible, reasonably simple, and has clinical relevance as judged by correlations with patient survival. Further study may demonstrate advantages from incorporation of the nuclear or cytologic characteristics of tumor cells into the Gleason system. Newer techniques of acid phosphatase determination, bone scans, and assessment of the regional lymph nodes should provide better staging criteria for correlation with primary tumor histology in the future. These workshops presented a unique opportunity for representative clinicians and pathologists in the United States to express their viewpoints in a comprehensive fashion on this timely and important topic.

Mammary carcinoma with osteoclast-like giant cells. A study of eight cases with follow-up data.

Abstract: Eight cases of a rare, distinctive variant of infiltrating mammary carcinoma featuring benign multinucleated osteoclast-like giant cells are reported. The multinucleated osteoclast-like giant cells are reported. The multinucleated giant cells were associated with ductal carcinoma in five cases and with infiltrating lobular carcinoma in three cases. Although three patients had lymph nodal metastases in level one, none of the nodal metastases contained giant cells. From the limited follow-up data of this report, it seems likely that the prognosis for patients who have this type of adenocarcinoma is not especially favorable. The observation that the giant cells generally occurred in areas of prominent angiogenesis suggests that the angiogenesis may be induced by some chemical substance produced by the tumor cells. Biochemical and immunologic investigations may eventually provide an explanation for this unusual morphologic manifestation of host reaction to mammary carcinoma.

Primary malignant giant cell tumor of bone: a study of eight cases and review of the literature.

Abstract: Eight cases of primary malignant giant cell tumor of bone were reviewed. There was a wide range in age from 17 to 76 years, with the sixth decade of life being the most common. The tumor was more frequent among females (male to female ratio--3:5). The most common sites of occurrence were in the region of the knee, with the distal end of femur and the proximal end of tibia affected in three and two cases, respectively. Pain and swelling of the involved regions were the most common complaints. The roentgenographic and pathologic features and the treatment were analyzed in detail. Although these cases were considered malignant, the follow-up periods varying from 4 to 15 years were available in six of the eight cases; only one patient died of tumor, 8 months after the surgical procedure. One patient died of unrelated cause, but the others were all alive with no evidence of disease. The pertinent literature was analyzed and examples of secondary malignant giant cell tumors of bone were compared to those of this present series to delineate differences in natural history and clinicopathologic features. It was clearly established that primary malignant giant cell tumor of bone is a separate entity with a more favorable clinical behavior, particularly if the disease process is eradicated early on either by cryosurgery, en bloc radical resection, or amputation.

A critical analysis of response criteria in patients with prostatic cancer treated with CIS‐diamminedichloride platinum II

Abstract: Cis-diamminedichloride platinum II (DDP), 50--70 mg/m2 iv, q 3w was administered to 25 patients with Stage D adenocarcinoma of the prostate. Since the assessment of tumor regression in a disease-oriented phase II study demands a clear end-point of response, case selection was restricted to patients who had objectively measurable lesions, i.e., nodes, skin, lung, and liver metastasis. Partial remission occurred in 3 (12%) and stabilization of disease in 1 patient. Responders lived 53 weeks vs. 20 weeks for non-responders. In the dosage and schedule used in this protocol, DDP was not an active agent in the treatment of prostatic cancer. Various patient characteristics are examined and correlations made between remission rates and survival in this study vs. 4 other response schemata. A critical analysis of patient selection, "lead time" -- diagnosis to chemotherapy, and the definitions of the terms "measurable" lesions, "evaluable" parameters, "objective response", stabilization of disease and response criteria employed in the 4 schemata are also discussed.

Increased Prostaglandin Synthesis by Macrophages from Tumor-Bearing Mice

Abstract: Prostaglandin E2 (PGE2) synthesis by macrophages was measured in normal and tumor-bearing mice. Splenic macrophages from C57BL mice bearing a transplantable, nonmetastasizing methylcholanthrene-induced fibrosarcoma produced significantly more PGE than cells from normal nontumor-bearing littermates. Augmented PG synthesis was found basally and after nonspecific stimulation of macrophages with endotoxin (LPS) and concanavalin A (Con A) as measured by radioimmunoassay. Resident peritoneal macrophages showed similar differences in radioimmunoassayable PGE levels. The conversion to prostaglandins of radiolabeled arachidonic acid previously incorporated into membrane phospholipids was followed over time. Macrophages from both normal and tumor-bearing animals incorporated equivalent amounts of tritiated arachidonic acid, showed similar distribution of label in phospholipid pools, and released equivalent amounts of labeled Arachidonic Acid and phospholipid. However, at both 3 and 18 hr of incubation, unstimulated macrophages from tumor-bearing animals released significantly more PGE2 and 6-keto PGF1α (the metabolite of prostacyclin) compared to macrophages from normal animals. Nonspecific stimuli (Con A and zymosan) greatly augmented PG production in both animal groups, with tumor-bearers greater than with normals. LPS caused little augmentation in basal PG secretion at 3 hr, but it greatly increased synthesis measured 18 hr later. In similar experiments, Moloney sarcoma virus (MSV) could be shown to augment PG synthesis in BALB/c mice bearing a transplantable MSV-transformed tumor line, but not in normal animals. No significant difference was noted in adherence, morphology, phagocytosis, or enzymatic activity when the resident macrophages from normal and tumor-bearing animals were compared, suggesting that they were at the same relative state of activation but differed in their capacity to synthesize prostaglandins.

Different sensitivity of chromatin to acid denaturation in quiescent and cycling cells as revealed by flow cytometry.

Abstract: quiescent nonstimulated lymphocytes as compared with interphase lymphocytes that have entered the cell cycle after stimulation by mitogens. The difference is seen after cell treatment with buffers at pH 1.5 (1.3-1.9 range) followed by staining with acridine orange at pH 2.6 (2.3-2.9). Under these conditions the red metachromatic fluorescence of the acridine orange-DNA complex is higher in quiescent cells than in the cycling lymphocytes while the orthochromatic green fluorescence is higher in the cycling, interphase cells. The results suggest that DNA in condensed chromatin of quiescent lymphocytes (as in metaphase chromosomes) is more sensitive to acid-denaturation than DNA in dispersed chromatin of the cycling interphase cells. The phenomenon is used for flow cytometric differentiation between G0 and G1 cells and between G2 and M cells. In contrast to normal lymphocytes the method applied to neoplastic cells indicates the presence of cell subpopulations with condensed chromatin but with DNA content characteristic not only of G but

Importance of the time interval between surgery postoperative radiation therapy in the combined management of head & neck cancer

Abstract: Twenty-two patients with advanced carcinomas of various head and neck sites were treated with surgical resection followed by elective postoperative radiation therapy. No patient had gross residual or recurrent disease at the time radiation therapy was started. The time interval from surgery to the start of radiation therapy varied from two and one half weeks to sixteen weeks; the median was seven weeks. Doses of radiation varied from 4500 rad to 5400 rad in five to five and one half weeks. One patient was lost to follow-up. Of the remaining twenty-one patients ten were alive with no evidence of disease (NED) at two to four years (48 %). We observed that 7 of 10 (70 %) of patients whose radiation therapy was started within seven weeks after surgery, were alive free of disease; however, only 3 of 11 (27 %) of those in whom there was a delay of seven weeks or more survived free of disease. Furthermore, in the former group there were virtually no local or regional recurrences, regardless of the stage of the disease, while in the latter group the incidence of local or regional recurrences was 64 %. These data suggest that delay in the start of postoperative radiation therapy, even in the absense of gross recurrent tumor, might adversely affect the results of combined surgical and radiotherapeutic management of head and neck cancers.