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Biomedical subjects

S Rafla

Publications and source records attributed to S Rafla.

At least 19 recordsLinked to original sources
PubMed2000

Design of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

The objectives of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial are to determine in screenees ages 55-74 at entry whether screening with flexible sigmoidoscopy (60-cm sigmoidoscope) can reduce mortality from colorectal cancer, whether screening with chest X-ray can reduce mortality from lung cancer, whether screening men with digital rectal examination (DRE) plus serum prostate-specific antigen (PSA) can reduce mortality from prostate cancer, and whether screening women with CA125 and transvaginal ultrasound (TVU) can reduce mortality from ovarian cancer. Secondary objectives are to assess screening variables other than mortality for each of the interventions including sensitivity, specificity, and positive predictive value; to assess incidence, stage, and survival of cancer cases; and to investigate biologic and/or prognostic characterizations of tumor tissue and biochemical products as intermediate endpoints. The design is a multicenter, two-armed, randomized trial with 37,000 females and 37,000 males in each of the two arms. In the intervention arm, the PSA and CA125 tests are performed at entry, then annually for 5 years. The DRE, TVU, and chest X-ray exams are performed at entry and then annually for 3 years. Sigmoidoscopy is performed at entry and then at the 5-year point. Participants in the control arm follow their usual medical care practices. Participants will be followed for at least 13 years from randomization to ascertain all cancers of the prostate, lung, colorectum, and ovary, as well as deaths from all causes. A pilot phase was undertaken to assess the randomization, screening, and data collection procedures of the trial and to estimate design parameters such as compliance and contamination levels. This paper describes eligibility, consent, and other design features of the trial, randomization and screening procedures, and an outline of the follow-up procedures. Sample-size calculations are reported, and a data analysis plan is presented.

Colorectal Neoplasms↗
PubMed1998

Augmented therapy of extensive Hodgkin's disease: radiation to known disease or prolongation of induction chemotherapy did not improve survival--results of a Cancer and Leukemia Group B study.

PURPOSE: This prospective randomized trial in extensive untreated Hodgkin's disease was undertaken to assess the potential benefit of augmented therapy (12 months chemotherapy or radiation to known disease) compared to standard 6 months chemotherapy. PATIENT AND METHODS: A total of 258 patients, mostly Stage IV, were randomized to four treatment regimens consisting of six cycles of CCNU, vinblastine, procarbazine, and prednisone (CVPP); 12 cycles of CVPP; six cycles of CVPP followed by 25 Gy radiotherapy; or three cycles CVPP, 25 Gy radiotherapy, and three cycles CVPP. RESULTS: Complete remissions were achieved in 65% of all patients. A 58% overall 5-year survival rate was obtained. Relapses in irradiated areas of known disease occurred in only 6% of responding patients. There was, however, no statistical difference in response frequency, disease-free survival, or overall survival among the four regimens. Elderly patients responded less frequently. CONCLUSION: While radiotherapy provided control of local (known) disease, no impact on overall survival was apparent. Likewise, doubling the duration of chemotherapy did not improve response or survival. Augmentation of therapy with either radiotherapy or more chemotherapy in this study was of no benefit compared to the standard 6 months of treatment.

Adult↗
PubMed1997

The need to educate primary care physicians to provide oncologic services: a changing focus.

BACKGROUND: The traditional role of primary care physicians (PCPs) in cancer care has been primarily cancer detection, and their training and education were similarly oriented. Propelled by the changing health care delivery system, this role is now expanding substantially. METHODS: A survey of 31 health maintenance organizations active in the New York market area was performed. The HMOs were grouped into three main categories according to method of payment of the physician. Patient care responsibilities vary depending on the method of payment but stay constant within the group. Of 19 HMOs that responded to the survey, 13 had shifted much of the responsibilities for diagnosis and treatment decisions to the PCP. RESULTS: A national survey of all academic radiation oncology program directors in the United States, as well as training programs of primary care physicians, showed a unanimous lack of educational or training programs or opportunities to familiarize the PCP with radiation oncology as a therapeutic discipline and with its after-therapy requirements. This deficiency extended also to multimodality training and other aspects. The internal medicine programs surveyed scored only an average of 1.25 out of a possible 5 in education areas directly related to oncology training. These programs comprised 78% of the residents of all programs surveyed. CONCLUSION: The information gathered from these surveys reveals a shift towards mandating the provision of oncologic services by PCPs, who have inadequate training in oncology, with no system in place to remedy the deficiencies except on-the-job training. The inevitability of the changing role of the PCP must be accompanied by either an expansion of residency programs to encompass training in important aspects of oncology care or expansion and formalization of continuing education programs to achieve the same objective.

Aftercare↗
PubMed1993

Hodgkin disease in patients 60 years of age or older. Histologic and clinical features of advanced-stage disease. The Cancer and Leukemia Group B.

BACKGROUND: This article reviews the salient pathologic and clinical features of 171 patients with Stage III-IV disease who were 60 years of age or older who were treated on four Hodgkin disease (HD) protocols from 1969 to 1988. METHODS: Pretherapy sections were reviewed centrally for correlation of the histologic classification with anatomic sites of involvement and survival. RESULTS: The diagnosis of HD was confirmed in 114 (66.7%) patients. Non-Hodgkin lymphomas (NHL) and a miscellaneous non-HD group accounted for 52 (30.4%) and 5 (2.9%) of the cases. The overall median survival times of patients with Stage III-IV HD and NHL who were 60 years of age or older in the four protocols were not significantly different (1.5 versus 1.3 years, respectively; P = 0.28). There also was no significant correlation between the survival of these patients with HD and either the Rye classification, 19 specific histologic parameters, or the British National Lymphoma Investigation grading system for HDNS. In the last protocol, the 5-year survival rate of patients with HD who were 60 years of age or older was lower than that of patients 40-59 years of age or that of those younger than 40 years of age (31% versus 63% versus 79%, respectively, P < 0.0001). Patients with HD entered into the two most recent protocols showed lower incidences of involvement of cervical and iliac-inguinal-femoral lymph nodes and skin-subcutaneous tissues than the patients with NHL who were misdiagnosed as HD. Moreover, patients with Stage III-IV HD in the most recent protocol who were 60 years of age or older had lower rates of involvement of the cervical and mediastinal-hilar lymph nodes and a higher rate of involvement of the gastrointestinal tract than younger patients. CONCLUSIONS: Patients with Stage III-IV HD and NHL who are 60 years of age or older differ with respect to the rates of involvement of specific anatomic sites but not in survival when treated with HD protocols. In contrast, patients of different age groups with Stage III-IV HD disease differ with regard to the rates of involvement of anatomic sites and survival.

Age Factors↗
PubMed1991

Effectiveness of radiotherapy with radical neck dissection in cancers of the head and neck.

A retrospective analysis of 457 radical neck dissections performed over a 30-year period for cancers of the oral cavity, pharynx, and larynx was carried out. Two hundred thirteen patients underwent radiotherapy to the primary cancer site and/or to the neck. Of these, 164 underwent perioperative adjuvant radiotherapy and 24 underwent definitive radiation for cure and were followed up by salvage surgery. Thus, 188 patients received radiotherapy for nonrecurrent disease. Twenty-five additional patients underwent radiation for surgical failure following radical neck dissection. The goal of the study was to determine whether radiotherapy altered the course or end result of the disease. The T and N stage at onset of disease was similar for the radiotherapy and nonradiotherapy groups. Preoperative radiotherapy was effective in down staging the disease at the primary site and, to a lesser extent, in the lymph nodes, but had limited impact on survival. Failure to control the disease in the neck occurred in 60 (32%) of the 188 patients who received radiotherapy for primary disease; recurrence rates were lower in the combined therapy group than in the surgical group of patients with N2 and N3 stages of disease. The 3-year disease-free survival was 45%; this was no better than the 63% survival rate in patients who did not receive radiotherapy, although survival was better in the combined therapy group for patients with N3 stage of disease. The worst results were in those patients who were irradiated for surgical failure (14% survival); the 24 patients who required salvage radical neck dissection following failure of definitive radiotherapy for cure had a 42% survival.

Adult↗
PubMed1989

Recurrent tumors of the head and neck, pelvis, and chest wall: treatment with hyperthermia and brachytherapy.

Cancer that recurs after surgery and radiation therapy remains a major problem. The claimed effectiveness of thermobrachytherapy in patients with this problem prompted the present study. Forty-six lesions (20 head and neck, 18 pelvic, seven chest wall, and one limb sarcoma) in 38 patients were treated with interstitial hyperthermia that sandwiched the use of Ir-192 with the aim of delivering 2,000-6,000 cGy, depending on prior dose and tissue tolerance. Complete regression occurred in 19 (54%) of 35 evaluable cases. More than 58,000 measured temperature points were analyzed to develop a representative quantitative measure, the "modal thermal dose," that represented the temperature reported most often during heating sessions. The pattern was plotted in each case. No significant relation was found between heating patterns and tumor response. Of all the prognostic factors studied, the radiation dose was the most significant, with a complete response rate being 78% when the total radiation dose exceeded 6,000 cGy, compared with 8% when the dose was lower than 5,000 cGy (P less than .005). The tumor volume also was important, with smaller lesions responding much better than larger ones (P = .1).

Brachytherapy↗
PubMed1988

Changes in T-cell subsets after radiation therapy.

The T-cell subsets of 129 patients with cancer were counted before and after radiation therapy. The cells were labeled with monoclonal antibodies that were specific for each type of T cell. Significant changes after therapy were decreases in the proportion of T-helper/inducer cells, pan-T cells, and in the ratio of T-helper/inducer to T-suppressor/cytotoxic cells. There was an increase in the percentage of T-suppressor/cytotoxic cells. When the site of the primary cancer was considered, genitourinary cancer and cancer of the head and neck both showed a decreased percentage of T-helper/inducer cells and a reduced ratio of T-helper/inducer to T-suppressor/cytotoxic cells. The percentage of pan-T cells in head and neck cancer and the ratio of T-helper/inducer to T-suppressor/cytotoxic cells in breast cancer were decreased. The percentage of T-helper cells was particularly decreased by radiation therapy in advanced stages of cancer, in higher grade tumors, and in larger tumors. The absolute numbers of various T-cell subsets were decreased in all groups.

Antibodies, Monoclonal↗
PubMed1988

Vincristine and prednisone prolong the survival of patients receiving intravenous or oral melphalan for multiple myeloma: Cancer and Leukemia Group B experience.

A total of 589 patients with previously untreated multiple myeloma were randomized to receive daily oral melphalan, pulse-dose intravenous (IV) melphalan, carmustine (BCNU), or lomustine (CCNU). All patients received an initial tapering course of prednisone (Pred). During week 22 (day 154), patients were randomized to receive or not to receive additional therapy with vincristine (VCR) (1 mg/m2) and prednisone (0.6 mg/kg/d for seven days) at 8-week intervals. The influence of VCR/Pred was determined in 302 patients who remained on study beyond 22 weeks after initial therapy. VCR/Pred converted a significant percentage of nonresponders to responders in patients treated with melphalan (55% v 19%, P = .002), but not in patients treated with a nitrosourea (48% v 23%, P = .06). Survival beyond week 22 was significantly longer following the addition of VCR/Pred in patients receiving melphalan (median, 35.3 months v 27.0 months; P = .003) but not in patients receiving BCNU or CCNU (median, 28.1 months v 26.2 months; P = .91). These differences were seen both for oral and IV melphalan. A trend for beneficial effect of VCR/Pred was definitely seen in the good-risk patients (P = .03) but only suggestive for poor-risk patients (P = .12). Following adjustment for VCR/Pred effects, there were no differences in the survival of patients receiving any of the four initial treatments.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

A brief POMS measure of distress for cancer patients.

The authors describe an 11-item short form of the Profile of Mood States' 58-item Total Mood Disturbance Score (TMDS). The Brief TMDS was derived from a sample of 619 adults with mixed cancer diagnoses, and replicated on a second sample of 295 lung cancer patients. Internal consistency of the Brief TMDS and the correlations of the Brief TMDS with the full TMDS were highly satisfactory for both samples. Given the difficulty many medically ill people have with lengthy self-report scales, and the increasing importance of measuring distress as an adjunct to patient care, this measure shows promise as a rapid, reliable tool.

Affect↗
PubMed1986

Single, sequential, and multiple alkylating agent therapy for multiple myeloma: a CALGB Study.

Four intravenous (IV) alkylating agent regimens were tested in 615 previously untreated patients with multiple myeloma. Patients were randomized to receive melphalan, cyclophosphamide, and carmustine in combination (MCBP), sequentially (Seq-MCBP), or in combination with doxorubicin (MCBPA). The fourth group received IV melphalan (MP) as the only alkylating agent. All groups received a tapering dose of prednisone. Toxicity was similar for all regimens although the nadir of cytopenia was reached more quickly for the regime including melphalan only. Response as measured by reduction in myeloma protein or other parameters were similar for the four treatments. Survival was significantly poorer for the group receiving the alkylating agents in sequence. The survival of high tumor cell load patients who were azotemic was better in the groups treated with IV MP or with the combination of IV MCBP. In view of the simplicity and probable cost savings attached to single-agent treatment, a melphalan/prednisone regimen should be considered as initial therapy for all patients with myeloma.

Adult↗
PubMed1985

Temperature effect on mitoxantrone cytotoxicity in Chinese hamster cells in vitro.

The effect of heat on 1,4-dihydroxy-5,8-bis[2-[(2-hydroxyethyl)amino]ethylamino]-9, 10-anthracenedione dihydrochloride (DHAD; mitoxantrone, NSC 301739) cytotoxicity was studied in V79 Chinese hamster cells. An overnight exposure to the drug at 40 degrees C enhanced drug damage in chromosome aberrations, culture growth, and cellular reproductive integrity. Preincubation of cells overnight in medium containing no drug at this temperature also showed some enhancement in subsequent DHAD lethality (at 37 degrees C as well as 43 degrees C). Short exposures (1 h) to DHAD at 43 degrees C was more damaging than were exposures at 37 degrees C. This was also true for cells in the plateau phase of culture growth. As compared with exponentially growing cells, plateau-phase cells were more resistant to DHAD.

Animals↗
PubMed1984

Efficacy of daunorubicin in the therapy of adult acute lymphocytic leukemia: a prospective randomized trial by cancer and leukemia group B.

The efficacy of the addition of intensive therapy with daunorubicin (45 mg/m2 IV on days 1, 2, 3) to an otherwise identical induction program consisting of vincristine, prednisone, and L-asparaginase was assessed in 177 previously untreated adults (greater than or equal to 20 years of age) with acute lymphocytic leukemia (ALL). In the prospectively randomized phase of the investigation, 46 patients received daunorubicin in induction, whereas 53 did not. The two groups were otherwise comparable for pretreatment variables. A complete response was observed in 38/46 patients (83%) treated with daunorubicin, compared to 25/53 (47%) induced with vincristine, prednisone, and L-asparaginase alone (P = .003). The high response rate attributable to the use of the anthracycline was confirmed by the nonrandomized treatment of 78 subsequent patients, in whom a complete response rate of 76% was attained. A common program for central nervous system therapy and for maintenance therapy was employed in 103 patients achieving complete response. Maintenance consisted of cycles of 6-mercaptopurine (6-MP) and methotrexate with periodic reinforcement with vincristine and prednisone. Maintenance therapy proved to be minimally toxic. The average duration of complete response was 15 months and was not affected by the induction program employed. Approximately 25% of responders are projected to remain in continuing complete response for 36 months. The failure of the daunorubicin-containing programs to produce a higher percentage of long-term survivors, despite the higher complete response rates achieved, was thought to be due to the use of a maintenance program that was weak in intensity and dependent on reinforcement with vincristine and prednisone. These data clearly establish the increased effectiveness of vincristine, prednisone, L-asparaginase, and daunorubicin, as compared to this combination without daunorubicin, in the induction of complete response in adults with ALL. The results support the concept of an intensive, rather than a conservative, chemotherapeutic approach as the most appropriate strategy for the treatment of adult ALL.

Adult↗
PubMed1983

Effect of spirogermanium on V79 Chinese hamster cells.

Chinese hamster V79 cells were exposed to spirogermanium (SG), and their mitotic activity, population growth, plating efficiency, viability (dye exclusion), and clonogenicity were assayed. Mitotic frequency of cultures in SG decreased initially with increasing drug concentration and later plateaued at varying levels depending on drug concentration. Cultures continuously exposed to SG showed drug concentration-dependent growth inhibition, with no effect at 0.1-0.2 micrograms/ml and increasing toxicity above 0.5 microgram/ml. Cytolysis was enhanced by the simultaneous presence of amphoterocin B and by exposing cells to SG at 42 degrees C. Hypoxia protected cells from drug-induced lysis. The loss of membrane-intact cells was inversely related with population density at the time of drug exposure. Short exposures (up to 5 hours) at 20 micrograms/ml showed that cell killing was primarily through reduction of dye-excluding cells within a matter of hours and secondarily through loss of proliferative capacity. Prolonged drug contact (24 hours) at lower concentrations (1-5 micrograms/ml) accentuated the effect on clonogenicity. These results suggest that for clinical potency, prolonged drug contact may be beneficial.

Amphotericin B↗