PubMed Health⌕ Search

Biomedical subjects

A S Glicksman

Publications and source records attributed to A S Glicksman.

At least 19 recordsLinked to original sources
PubMed1992

Preoperative combined chemotherapy and radiation therapy plus radical surgery in advanced head and neck cancer. Five-year results with impressive complete response rates and high survival.

Radiation therapy combined with cisplatin as a chemoradiation sensitizer (CT/RT) has been reported to enhance tumor response in squamous cell carcinoma of the head and neck. In the present study, CT/RT was used preoperatively in advanced Stage III and IV head and neck cancer. Fifty-three patients were entered prospectively into a Phase II study. Treatment consisted of 4500 cGy of radiation therapy in 5 weeks combined with cisplatin 20 mg/m2 for 4 days during weeks 1 and 4 of radiation therapy. This was followed 4 to 8 weeks later by curative surgery. Pretherapy dental care; long-term nutritional support; individualized skin, mouth, and wound care; and continuous interdisciplinary communication were integral parts of this regimen. In four patients, CT/RT toxicity was seen (8%); three episodes of skin reaction or stomatitis and three episodes of leukopenia (less than 2500/microliters), causing a delay in CT/RT treatment in one patient. Three patients died of other causes during the preoperative interval, without clinical evidence of toxicity. Fifty patients (94%) had a complete (CR) or partial response (PR) to CT/RT. Clinical CR was seen in 38 of 51 (75%) primary tumors and 21 of 27 (78%) cervical nodes. Forty-one patients (77%) underwent curative surgery. In 27 of 32 (84%) resected CR primary tumors and 16 of 18 (89%) CR metastatic nodes, the surgical specimen was microscopically free of tumor. Postoperative morbidity was 32%. Five patients (12%) required additional surgery for their complications. Perioperative mortality was 5%. Five patients had tumor recurrence: three postoperatively after clinical PR to CT/RT and two in clinical CR patients who refused further treatment after CT/RT, then had a recurrence and were salvaged surgically. No patient with a CR in both the tumor and nodes who underwent surgery had a tumor recurrence. With a follow-up of 8 years (median, 40 months), the median survival for all patients was 45 months. The 5-year actuarial survival rate was 43% for all patients and 55% for patients who had CT/RT and surgery. This multimodality treatment of advanced head and neck cancer has low toxicity and impressive survival. It renders a significant number of patients tumor-free before surgery. These patients may be candidates for additional study triaging additional CT/RT for complete CR only and surgery for PR and biopsy-proved residual disease.

Adult↗
PubMed1992

Preoperative chemotherapy and radiation therapy for stage IIIa carcinoma of the lung.

Thirty-six patients with stage IIIa histologically proven non-small cell carcinoma (T3 N2 or T2 N2) underwent concomitant radiation therapy and chemotherapy before pulmonary resection. The therapy consisted of two cycles of continuous infusion of cis-platinum, 25 mg.m-2.day-1 (days 1 through 4) every 4 weeks and concomitant irradiation, 55 Gy, of the tumor and mediastinum. Two to 3 weeks after treatment, the patients were reevaluated for thoracotomy and pulmonary resection. Five patients were found to have unresectable lesions. Thirty-one patients had complete resection, 27 by radical pneumonectomy and 4 by radical lobectomy, giving a resectability rate of 86%. Complete sterilization of lung tumor and mediastinal nodes proven histologically was achieved in 10 patients (28%) and 17 patients (47%). The 3-year survival rate is 61.7% for patients who had resection. Median follow-up is 27 months (range, 6 to 61 months). The preliminary study indicates that preoperative cis-platinum and concomitant radiation therapy is tolerated, appears to increase resectability, and may improve survival in patients with stage IIIa lung cancer.

Adult↗
PubMed1992

The structure for a radiation oncology protocol. The Committee of Radiation Oncology Group Chairmen.

Multi-institutional Cooperative Group clinical trials involving radiotherapy require unambiguous therapeutic guidelines, so that patients entered from each of the participating institutions will receive essentially uniform treatment. The technical guidelines for a Radiation Oncology Protocol presented in this report represents a consensus of the Radiotherapy Committees in the major NCI funded Cooperative Groups and is derived from over a decade of experience. Although they have been written for external beam therapy, they are applicable to brachytherapy with appropriate technical considerations. It is anticipated that further evolution will occur with the introduction of new technologies such as 3-D treatment planning and delivery, multi-leaf collimation and small field irradiation.

Clinical Protocols↗
PubMed1991

The effects of postinduction intensification treatment with cytarabine and daunorubicin in adult acute lymphocytic leukemia: a prospective randomized clinical trial by Cancer and Leukemia Group B.

Cancer and Leukemia Group B undertook a randomized trial of intensification treatment in adults aged 15 to 79 years with acute lymphocytic leukemia (ALL) in complete remission (CR). Daunorubicin (DNR), prednisone, vincristine (VCR), intrathecal (IT) methotrexate (MTX), and asparaginase produced 177 CRs in 277 patients. One hundred fifty-one patients were randomly assigned to receive treatment as follows: 74 received intensive cytarabine and DNR, and 77 received cycles of mercaptopurine (6-MP) and MTX, followed by 6MP, MTX, VCR, and prednisone for 3 years in all. One hundred twelve patients received CNS prophylaxis. Intensification produced major myelosuppression but did not improve remission duration (median, 21 months). Of the 151 patients with CRs who entered the intensification phase, 29% remain in continuous CR (43 to 117 months); in 19 patients, CRs have lasted for longer than 7 years. No relapses occurred after 60 months. Median survival from the time of randomization was 30 months. Those under 30 years of age responded more frequently, with longer CR and survival. While 53% of those aged 15 to 19 years remain in continuous CR, 92% of patients over 59 years have relapsed. The presence of a myeloid antigen on the leukemic cells was adversely prognostic for CR achievement and for survival. Pretreatment WBC and platelet levels independently affected CR duration and survival. Early M1 marrow development presaged longer remissions. CNS relapse occurred in 47 of 256 patients with normal CSF before treatment, in 29 before CNS prophylaxis. CNS disease occurred after CNS prophylaxis in 18 patients: 13 of 61 who had received standard premaintenance and five of 51 who received intensification. No advantage in CR duration or survival resulted from intensive treatment with DNR and cytarabine following induction of CR.

Adolescent↗
PubMed1990

Radiation qualities of x-ray beams in cooperative clinical trials.

X-ray beams are usually described by "MV" numbers which represent accelerating potentials (AP) and approximations to the maximum energies in the photon spectra. However, these numbers do not uniquely specify the properties of the beams. Current high energy photon dosimetry protocols specify radiation quality in terms of a measured ionization ratio which is equivalent to the ratio of the tissue-maximum ratios at depths 10 cm and 20 cm, for field size 10 cm X 10 cm [TMR)20(10]. For convenience, the American Association of Physicists in Medicine introduced a new parameter, known as the Nominal Accelerating Potential (NAP), which was derived from (TMR)20(10) and features values in MV units that are similar to those of the conventional accelerating potentials. (TMR)20(10) and Nominal Accelerating Potential may be considered to be expressions of the penetrating powers of x-ray beams. We determined (TMR)20(10) and Nominal Accelerating Potential for 460 treatment machines with stated accelerating potentials from 4 MV to 25 MV in the Quality Assurance Review Center's files of machine data from institutions that participate in cooperative clinical trials. The results demonstrate appreciable variability of the two parameters at each stated accelerating potential, with overlapping of adjacent groups of machines. It is concluded that the manufacturers' MV numbers do not reliably identify x-ray beams in terms of their depth dose properties. To promote standardization and consistency of energy specification in clinical trials as well as in general practice, we propose that x-ray beams be designated by their Nominal Accelerating Potential values as an adjunct to the use of (TMR)20(10) in radiation therapy.

Humans↗
PubMed1990

The influence of patient age on the diagnosis and treatment of lung and colorectal cancer.

We examined the relationship between patient age and medical care received by patients diagnosed with the following two common cancers: non-small-cell lung cancer and colorectal cancer. Controlling for the influence of sex, marital status, presence of comorbid disease, and socioeconomic status, we found that age was not related to the diagnostic tests ordered for either cancer type. However, lung cancer patients with local disease who were older than age 74 years underwent definitive surgical treatment less often than did younger patients. Few patients at any age (less than 9%) with colorectal cancer did not undergo definitive surgical treatment. Patients with regional colorectal disease who were older than 74 years of age underwent radiation therapy to the abdomen less often than did younger patients. These results add to the growing body of literature suggesting that older cancer patients are less likely to undergo the same type of care received by younger patients.

Age Factors↗
PubMed1989

Field matching considerations in craniospinal irradiation.

Radiotherapy of the craniospinal axis in leukemia and medulloblastoma patients usually involves parallel-opposed lateral cranial fields adjacent and orthogonal to a posterior spinal field. Most current treatment protocols require rotation of the cranial fields to compensate for the divergence of the spinal field such that the adjacent field edges abut along the match line in the mid-saggital plane. Some departments introduce gaps up to 1-2 cm wide between the matched fields out of concern for overdosing the spinal cord. The behavior of the dose distribution was studied in the junction region of divergence-compensated fields as the separation of their edges varied from 0.5 cm overlap to a gap 1 cm wide. Composite dose profiles and isodose maps were calculated for 60Co and 4 MV photon beams using static and moving junction (feathering) techniques. When the fields are appropriately matched there is no gap between them in the mid-saggital plane and the dose varies smoothly across the junction. Gapping of divergence-compensated fields is detrimental to dose uniformity, producing underdosage in a volume that extends to all depths in the body. With proper localization, there is no way that the commonly accepted critical dose for myelopathy can be exceeded in typical treatments of leukemia patients. It can occur in the treatment of medulloblastoma patients only in the unlikely situation where there is gross overlapping of the adjacent fields. Feathering may be considered as a safety margin against spinal cord damage in medulloblastoma but it is superfluous in leukemia. The importance of treatment machine quality assurance and verification of patient set up geometry are emphasized.

Humans↗
PubMed1989

Competitive exclusion of clonal subpopulations in heterogeneous tumours after stromal injury.

Xenografted artificial heterogeneous tumours (AHTs) were created by admixing, in a ratio of 9:1 or 1:9, two clonal subpopulations (designated as clones A and D) obtained from a heterogeneous human colon adenocarcinoma. In unperturbed AHTs these percentages remain constant with increasing tumour size. At average volumes of 250 mm3, AHTs were X-irradiated (15 Gy) and changes in growth rate and composition assayed. A and D cells exhibited equivalent levels of survival after in vivo irradiation as determined by excision assay procedures. At about 2-3 weeks post-irradiation AHTs exhibited a significant enrichment of the majority population in both the 1:9 or 9:1 A:D AHTs. Additional studies were concomitantly performed to determine whether these changes were mostly a function of normal tissue damage or of parenchymal tumour cell killing. In these studies, the normal tissue only was irradiated, tumour cells were implanted one day after irradiation, and the composition of AHTs assayed as a function of time post-irradiation. In these studies, similar shifts in composition with similar kinetics to that seen in the in situ irradiations were found. We therefore propose that these compositional shifts are mainly a reflection of radiation damage to the stromal microenvironment, which is consequently unable to support tumour growth adequately leading to competitive exclusion of the minority subpopulation.

Animals↗
PubMed1988

Lung, breast, and colorectal cancer: the relationship between extent of disease and age at diagnosis.

We examined the relationship between age and extent of disease at initial diagnosis as part of a population-based, prospective study documenting the patterns of care received by over 1500 newly diagnosed lung, breast, and colorectal cancer patients identified in nine Rhode Island hospitals. For each cancer site examined, no age by extent of disease relationship was observed; however, analysis by sex among lung cancer patients indicated an inverse age relationship for men. The absence of an age effect for breast cancer patients is in contrast to earlier research findings that identify a positive association between extent of disease and age at diagnosis. Past results may reflect age-related differences in patient and physician screening behavior characteristic of earlier time periods.

Age Factors↗
PubMed1988

Radiobiological considerations of brachytherapy.

The special radiobiological effects of low dose-rate radiation on tumors and normal tissue are in large part responsible for the effectiveness of brachytherapy. There is good reason to believe that improvement in local tumor control can be expected by the addition of chemotherapeutic agents, specifically designed radiation sensitizers, and differentiation-inducing agents, as well as by the manipulation of dose rates and dose distributions. This can be an important contribution to cancer management in the future and is an exciting area for further study.

Animals↗
PubMed1987

Tumor micro-ecology and competitive interactions.

Three nested models describing the growth of individual subpopulations in a heterogeneous environment are described. The models represent the dynamics of two populations which compete, to varying degrees, for common resources. The first model describes growth in a totally non-competitive micro-environment, the second model describes an ecology in which competition is proportional to competitor population size, and the third model ecology extends the model described by Jansson & Revesz (1974), which allows one population to emerge from the other. The critical points for each model are defined using the isoclines derived from the Ordinary Differential Equations (ODE's) describing competitive growth. The critical points for each model are characterized by the signs of the eigenvalues of the variational matrix at each point. The theoretical results of the analysis show that a competitive model ecology with Verhulstian logistics allows four critical points: the origin which is a repeller, two competitive exclusion points, and an equilibrium state (Waltman, 1983). The extended model ecology of Jansson & Revesz (1974), allows three critical points: the origin which is a repeller, competitive exclusion of the first population, and an equilibrium point. Data from a human adenocarcinoma of the colon and murine mammary tumors are used as qualitative measures of the dynamics of the three micro-ecologies. Issues such as stochastic extension to model small populations either for clonal extinction or heterogeneous emergence are discussed.

Adenocarcinoma↗
PubMed1987

Technical structure of a radiotherapy protocol.

Multi-institutional cooperative group trials require conformity to a uniform set of therapeutic guidelines so that all patients entered on the study are treated the same regardless of which participating center enters the case. This can come about only if an unambiguous, clearly defined treatment program is included in the protocol. Examples of confusing protocol guidelines from recent Group studies demonstrate how well-meaning participants can inadvertently deviate from study requirements. The Quality Assurance Review Center has developed an outline for the radiotherapy component of a study which has alleviated this problem considerably.

Clinical Trials as Topic↗
PubMed1987

Growth in solid heterogeneous human colon adenocarcinomas: comparison of simple logistical models.

Three models of simple logistical growth were used to describe volumetric growth in heterogeneous tumours. Two clonal subpopulations (designated as clone A and clone D) originally obtained from a human colon adenocarcinoma were used to produce solid xenograft tumours in nude mice. Volumetric growth of tumours produced from pure cells alone was compared to that produced from 50% A:50% D, 88% A:12% D, and 9% A:91% D admixtures. Gompertzian analysis of the in vivo growth data indicated significant differences in both the initial growth rates and final asymptotic limiting volumes of the pure versus the admixed tumours. Verhulstian and modified Verhulstian models were also used to derive regression curves from the same data. The fit of the curves was compared with each other using standard (Akaike, 1974; Schwartz, 1978) information criteria. In four of the five tumour populations the Gompertz equation fitted best. Only in the 88% A:12% D tumours did the modified Verhulst model fit best. The deviations from the regression curves, the residuals, for all three models were systematically distributed. These systematic errors are likely to be the result of using simplified logistical models to describe the growth kinetics of interacting populations in heterogeneous tumours.

Adenocarcinoma↗
PubMed1987

A technique to analyse the emerging zonality of heterogeneous solid tumours.

A technique to analyse the time-dependent emergence of homogeneous regions composed of cells from a single clone within an artificial (clonally) heterogeneous tumour is described. Neoplasms were grown in vivo as xenografts made from varying proportions of the dichotomous subpopulations (Clones A and D). They were sampled frequently for volume and composition. A variable number of tumour cross-sections were taken as part of the sampling technique. The random subsamples obtained from each cross-section were enzymatically disaggregated into single cells. From the single cell disaggregates the composition of the tumours was estimated. An estimator for the global proportion of cells was then calculated from all the single cell disaggregates. Time-dependent changes in the overall composition of the tumour requires that a time-dependent estimate of the global proportions of the subpopulations be calculated from each sample. Analysis of the sample proportions results in a statistic which can be tested for goodness-of-fit against a standardized normal variate as a test of emerging zonality. Data from three artificial admixtures were examined. The results show that 'zonality', i.e. regions composed primarily of single subpopulations, emerges in all cases. However, the rate at which the zones emerge appears to depend on the 'compositional stability'. Robustness studies show that the technique is robust with respect to the global estimator of the proportion.

Adenocarcinoma↗