Biomedical subjects

B Glimelius

Publications and source records attributed to B Glimelius.

At least 127 records · Page 7Linked to original sources

PubMed1998

The Swedish National Care Programme for Anal Carcinoma--implementation and overall results.

The Swedish National Care Programme for Anal Carcinoma (SNCPAC) was instituted in order to create a uniform handling policy for anal cancer and thus to accrue a population-based material allowing unbiased analyses. This study evaluates the degree of implementation of the SNCPAC guidelines, and presents overall treatment results in a total of 356 patients with epidermoid cancer of the anus and the perianal region diagnosed in Sweden between 1985 and 1989. Primary treatment according to the guidelines was irradiation up to 40 Gy, Bleomycin was administered intramuscularly before the first 18 fractions. After a 3-week pause, radiotherapy was to be continued up to a dose of 60-64 Gy, if at least an almost complete response was achieved. Otherwise, the patient was recommended surgery within a week. The guidelines were applied in 90%, of cases where such treatment was possible. The 5-year tumour-specific survival rate was 72%. The survival rate was more favourable in perianal tumours (90%) than in anal canal tumours (68%, p < 0.01). The 5-year probability of having a preserved anus was 64% (anal canal/perianal 58%/91%, p < 0.001). Bleomycin did not appear to have any effect on treatment results. The care programme has had a rapid and almost complete nation-wide penetration, and h as created the desired uniformity allowing proper analyses. The treatment results also appear comparable with specialised referral centres.

Adult↗

PubMed1998

Evaluation of clinical benefit of chemotherapy in patients with upper gastrointestinal cancer.

A new endpoint, the Clinical Benefit Response (CBR), was recently suggested as a means of measuring the effectiveness of palliative chemotherapy in patients with pancreatic cancer. We took advantage of extensive recordings of measurements of treatment effects in two trials in patients with gastrointestinal cancer in order to assess the relevance of CBR criteria. In 151 patients, 53 with pancreatic cancer, 37 with biliary cancer and 61 with gastric cancer, who were randomized between chemotherapy with best supportive care and best supportive care alone, CBR criteria were applied retrospectively to the evaluations of the effects on the patients' well-being made by the treating physician and by the patient in quality-of-life questionnaires, chiefly EORTC QLQ C-30. When compared with subjective response evaluations made by both the physician and the patients' questionnaire data, it was found that CBR overestimated the beneficial effects in certain patients and underestimated them in others. The reason for this overestimation was mainly that the adverse effects of the chemotherapy were not considered appropriately. The underestimation was mainly due to the fact that CBR in practice is dominated by pain assessment, and alterations in other symptoms are also clinically relevant. CBR did, however, show the same differences between the two randomized groups as the subjective response evaluations and the quality-of-life estimations. It is concluded that CBR can be used as a method of measuring the beneficial clinical impact of a treatment strategy in clinical trials, but its limitations in reflecting several important aspects influencing the overall well-being of patients do, however, restrict its use. The criteria designed for use in patients with pancreatic cancer cannot be immediately applied to patients with other cancer types.

Adult↗

PubMed1998

Methyl-GAG, ifosfamide, methotrexate and etoposide (MIME) as salvage therapy for Hodgkin's disease: a prospective study.

This study presents the results of a prospective study of methyl-gag, ifosfamide, methotrexate and etoposide (MIME) as salvage regimen for Hodgkin's disease (HD) in Sweden. Sixty-four patients with recurrent or refractory HD were treated with MIME between July 1988 and December 1993. All patients except one had, earlier, been treated with and failed consecutive or alternating MOPP and ABVD. Median age was 37 yr (range 14-73). Twenty patients (31%) achieved a complete remission (CR) and 17 (27%) a partial remission (PR), giving an overall response rate of 58%. The 5-yr survival for all patients was 43%. In a multivariate analysis, the most important factors predicting a poor survival were the presence of extranodal disease at relapse, male gender and high age. Twenty-nine patients were treated with high-dose chemotherapy with stem-cell rescue after MIME. Those patients had a similar survival compared to the patients responding to MIME but not treated with high-dose chemotherapy. We conclude that MIME induces remissions in a high proportion of patients with recurrent and refractory HD with acceptable toxicity. The remissions probably need consolidation, but the nature of this consolidation is still controversial.

Adolescent↗

PubMed1998

Epoetin beta in the treatment of anemia in patients with advanced gastrointestinal cancer.

PURPOSE: The possibility that epoetin beta (EPO) could increase hemoglobin (B-Hb) levels and improve quality of life (QoL) in patients with advanced gastrointestinal cancers was investigated. PATIENTS AND METHODS: One hundred patients with gastric, pancreatic, biliary, or colorectal cancers and subnormal B-Hb levels were included in a randomized study to test low-dose EPO (2,000 U subcutaneously thrice weekly [2,000 group]) against a higher dose (10,000 U times three [10,000 group]). Eighty-four patients were treated with chemotherapy. QoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 instrument. RESULTS: At baseline, mean B-Hb was 108 g/L with no difference between the groups. In the 10,000 group, an increase in B-Hb (>10 g/L) was seen in 30 (73%) patients treated with chemotherapy, after a median of 4 weeks, whereas a corresponding increase in the 2,000 group was seen in 15 (30%) patients after a median of 10 weeks (P < .001). A difference in the proportion of responders (five of eight v one of eight) was also seen in the group of patients not treated with chemotherapy. The proportion of responders was independent of baseline endogenous serum EPO level or observed/predicted log10 serum (S)-EPO levels. Patients who demonstrated improved B-Hb levels also showed improvements in QoL parameters. Tumor response was usually also associated with QoL improvements. CONCLUSION: Treatment with EPO at a dose of 10,000 U thrice weekly can rapidly and safely increase B-Hb levels in a high proportion of patients with advanced gastrointestinal cancers. QoL is influenced by the B-Hb increase, but also by the course of the underlying malignancy. It is therefore difficult to define clearly the clinical relevance of the B-Hb increase as such.

Adult↗

PubMed1998

p53 mutations in cyclophosphamide-associated bladder cancer.

Cyclophosphamide is a known bladder carcinogen, with cumulative dose directly related to increased risk. There is no consensus, however, on which major cyclophosphamide metabolite (i.e., acrolein or phosphoramide mustard) drives bladder carcinogenesis. We examined 19 cyclophosphamide-related bladder tumors to test the hypothesis that they might contain somatic mutations in the p53 tumor suppressor gene that could link a specific metabolite to the etiology of these cancers. Forty-three % (9 of 19) of the cases had a mutation in p53, with a predominance at G:C bp (7 of 9, 77%), a preference for non-CpG sites (6 of 7, 86%), and frequent G:C-->A:T transitions (5 of 7, 71%). The p53 mutation spectrum of these cyclophosphamide-associated bladder cancers differed significantly from patterns reported for sporadic (P = 0.020), smoking-related (0.043), and schistosomiasis-linked (P = 0.002) tumors but not arylamine-associated neoplasms (P = 0.860). Differences between the cyclophosphamide and arylamine-associated spectra included an unusual degree of clustering of exon 6 mutations (43% versus 17%, respectively) and an absence of multiple mutations in the former. Notably lacking in our series were G:C-->T:A transversions, the principal mutation associated with acrolein. Instead, the mutation spectrum matches the phosphoramide mustard adduction sequences determined by a repetitive primer-extension assay (P = 0.024), indicating that this metabolite might be a key mutagen in cyclophosphamide-related bladder cancer.

Adult↗

PubMed1998

Childbearing and the risk of Hodgkin's disease.

The causes of Hodgkin's disease remain incompletely known, but a higher incidence in men than in women has prompted an interest in the role of female sex hormones and reproductive history. Available epidemiological data are, however, contradictory. We analyzed possible associations between parity, age at first birth, and the risk of developing Hodgkin's disease by a linkage between the Swedish Cancer Register and a nationwide Fertility Register. Among women born between 1925 and 1972, 917 cases with Hodgkin's disease and concomitant fertility information were identified. For each case patient, five age-matched controls were randomly selected among women in the Fertility Register. Conditional logistic regression was used to estimate odds ratios of Hodgkin's disease associated with a birth. We found a slightly and nonsignificantly reduced risk of Hodgkin's disease in ever-parous compared with nulliparous women. Among parous women, the number of children was unrelated to risk, whereas there was some evidence of an increased risk with late age at first birth in women under age 45 at diagnosis. No clear temporal relations between childbearing and subsequent risk were discernible in any parity or age group. Although uncontrolled confounding might have affected our results, they do not indicate that hormonal or immunological changes associated with childbearing play a role in the development of Hodgkin's disease.

Adult↗

PubMed1997

Objective responses after fractionated infusional brachytherapy of unresectable pancreatic adenocarcinomas.

BACKGROUND: The prognosis of unresectable pancreatic adenocarcinoma is poor. Therefore, the treatment potential of an intratumoral infusional brachytherapy using macroaggregated human albumin in combination with radioactive chromic phosphate [32P] was investigated in this group of patients. METHODS: Seventeen patients with unresectable tumors received intratumoral infusional brachytherapy. Treatment and assessment of response was performed with the aid of ultrasonography. RESULTS: Four patients had complete response with a duration ranging from 2-57 weeks and 5 patients had partial response with a duration ranging from 4-21 weeks, corresponding to an objective response of 53% (9 of 17 patients). Six of these patients were alive 33-57 weeks after treatment. Radiation necrosis was observed in 1 patient after a 19,000-gray cumulative radiation dose and a slight decrease in blood counts was observed in 2 patients. CONCLUSIONS: Intratumoral infusional brachytherapy using radioactive colloidal chromic phosphate has the potential to reduce inoperable pancreatic tumors with few side effects.

Adenocarcinoma↗

PubMed1997

Sexually transmitted infection as a cause of anal cancer.

BACKGROUND: The incidence of anal cancer has increased in recent decades, particularly among women. To identify underlying risk factors, we conducted a population-based case-control study in Denmark and Sweden. METHODS: We conducted telephone interviews with 324 women and 93 men in whom invasive or in situ anal cancer was diagnosed between 1991 and 1994, 534 controls with adenocarcinoma of the rectum, and 554 population controls. The interviews covered a wide spectrum of possible risk factors for anal cancer. Odds ratios were calculated by logistic regression. Specimens of anal-cancer tissue and samples of rectal adenocarcinomas were tested for human papillomavirus (HPV) DNA with the polymerase chain reaction. RESULTS: Multivariate analysis revealed consistent and statistically significant associations between measures of sexual promiscuity and the risk of anal cancer in both men and women. There was a significant trend toward an association between higher numbers of partners of the opposite sex in women (P<0.001) and men (P<0.05) and strong associations with a variety of venereal diseases. In women, receptive anal intercourse, particularly before the age of 30 years, and venereal infections in the partner were also associated with an increased risk (odds ratios, 3.4 and 2.4, respectively). Fifteen percent of the men with anal cancer reported having had homosexual contact, as compared with none of the controls (P<0.001). High-risk types of HPV, notably HPV-16, were detected in 84 percent of the anal-cancer specimens examined, whereas all rectal-adenocarcinoma specimens tested were negative for HPV. CONCLUSIONS: Our study provides strong evidence that a sexually transmitted infection causes anal cancer. The presence of high-risk types of HPV, notably HPV-16 (which is known to cause cancer of the cervix), in the majority of anal-cancer tissue specimens suggests that most anal cancers are potentially preventable.

Adult↗

PubMed1997

Blood transfusion and non-Hodgkin lymphoma: lack of association.

BACKGROUND: Non-Hodgkin lymphoma is the seventh most commonly diagnosed malignant condition worldwide, and its incidence has increased markedly in recent decades. Blood transfusions have been implicated as a possible risk factor for non-Hodgkin lymphoma. OBJECTIVE: To determine whether blood transfusions are associated with an elevated risk for non-Hodgkin lymphoma. DESIGN: Population-based, nested case-control study. SETTING: Nationwide cohort in Sweden. PATIENTS: 361 patients with non-Hodgkin lymphoma and 705 matched controls, nested within a population-based cohort of 96795 patients at risk for blood transfusion between 1970 and 1983. Prospectively collected information on exposure was retrieved from computerized transfusion registries. MEASUREMENTS: Odds ratios obtained from conditional logistic regression models were used as measures of relative risks. RESULTS: No association was found between blood transfusions and the risk for non-Hodgkin lymphoma when patients who had received transfusions were compared with patients who had not received transfusions (odds ratio, 0.93 [95% CI, 0.71 to 1.23]). A reduction in risk was seen among persons who received transfusion of blood without leukocyte depletion (odds ratio, 0.72 [CI, 0.53 to 0.97]). Risk was not related to number of transfusions, and no interaction was seen with latency after transfusion. CONCLUSION: The findings in this study do not support previous observations of an association between blood transfusions and the risk for non-Hodgkin lymphoma.

Adult↗

PubMed1997

Lack of correlation between EBV serology and presence of EBV in the Hodgkin and Reed-Sternberg cells of patients with Hodgkin's disease.

Epstein-Barr virus (EBV) is detected in Hodgkin and Reed-Sternberg (HRS) cells in up to 50% of patients with Hodgkin's disease (HD). HD patients have been reported to express high serum titers against EBV antigens, even prior to the diagnosis of HD. Patients with high serum titers have a poorer prognosis. The aim of this study was to examine the relationship between the presence of EBV in HRS cells and the antibody titers reactive with different EBV antigens. Frozen serum and histopathological tissues were available from 107 untreated HD patients diagnosed between 1979 and 1991. The presence of EBV in the HRS cells was evaluated with immunohistochemistry directed against the LMP-1 antigen and/or with in situ hybridization of EBER-1. Analyses were performed of serum titers against early antigen (EA), diffuse (IgA and IgG) and restricted (IgG), virus-capsid antigen (VCA) (IgA and IgG), and EBV-encoded nuclear antigens (EBNA, EBNA 1, EBNA 2A, EBNA 2B, EBNA 6). EBV was detected in 27/107 (25%) tumor specimens, with a higher proportion in the MC group 8/13 (62%) (p < 0.01). IgG VCA and EBNA were detected in 99/107 (93%), evidence of a previous EBV infection. There were no significant relationships between antibody titers reactive with different EBV antigens and detectable EBV in HRS cells. Furthermore, there did not appear to be any relationship between EBV serology or the presence of EBV in HRS cells and clinical outcome. The role of EBV in the development of HD, especially its relationship to the immunological response, remains unclear.

Adult↗

PubMed1997

Patients suffering from both Hodgkin's disease and non-Hodgkin's lymphoma: a clinico-pathological and immuno-histochemical population-based study of 32 patients.

The occurrence of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) appearing in the same individual indicates a closer relationship between the 2 diseases than previously believed. The purpose of our study was to analyze cases of HD and NHL in a defined population clinically, histopathologically and immunohistochemically to look for similarities indicating a common cellular origin. Between 1974 and 1994, 77 individuals were identified from the Swedish Cancer Registry and the National Health Care Programme for HD as potentially having both diagnoses. Thirty-two patients who had both HD and NHL were available for histo-pathological re-examination and immunohistochemical staining with CD30, CD15, LMP, p53, CD45 (LCA), CD3, CD45R0 (UCHL-1), L26, MB2 and CD45R (4KB5). The most common relation was HD preceding a high-grade malignant NHL (16 of 32 patients), unexpectedly often of T-cell phenotype (7 of 16 patients). The next common association was NHL of B-CLL type followed by HD (7 of 32 patients). At clinical presentation, the first lymphoma did not differ from lymphomas not associated with a second lymphoma, whereas the second one often appeared with a disseminated and aggressive clinical form. There was a significant correlation between the expression of p53 and LMP in first and second lymphomas. CD3 antibody was frequently expressed both in HD and NHL, whereas positivity for B-cell-related antibodies, CD30, CD15 and CD45R0, was less frequent and generally lower than previously described. The occurrence of HD and NHL in an individual is unusual. Tumour biological features common to both HD and NHL may indicate a similar cellular origin, regardless of the time interval between the diagnoses, and may contribute to the understanding of the pathogenesis of lymphoma.

Adolescent↗

PubMed1997

Improved survival with preoperative radiotherapy in resectable rectal cancer.

BACKGROUND: Adjuvant radiotherapy for rectal cancer has been extensively studied, but no trial has unequivocally demonstrated improved overall survival with radiotherapy, despite a reduction in the rate of local recurrence. METHODS: Between March 1987 and February 1990, we randomly assigned 1168 patients younger than 80 years of age who had resectable rectal cancer to undergo preoperative irradiation (25 Gy delivered in five fractions in one week) followed by surgery within one week or to have surgery alone. RESULTS: The irradiation did not increase postoperative mortality. After five years of follow-up, the rate of local recurrence was 11 percent (63 of 553 patients) in the group that received radiotherapy before surgery and 27 percent (150 of 557) in the group treated with surgery alone (P<0.001). This difference was found in all subgroups defined according to Dukes' stage. The overall five-year survival rate was 58 percent in the radiotherapy-plus-surgery group and 48 percent in the surgery-alone group (P=0.004). The cancer-specific survival rates at nine years among patients treated with curative resection were 74 percent and 65 percent, respectively (P=0.002). CONCLUSIONS: A short-term regimen of high-dose preoperative radiotherapy reduces rates of local recurrence and improves survival among patients with resectable rectal cancer.

Follow-Up Studies↗

PubMed1997

Pregnancy and risk of non-Hodgkin's lymphoma: a prospective study.

The etiology of non-Hodgkin's lymphomas (NHL), including chronic lymphocytic leukemia (CLL), is likely to be related to immune function. In the light of the established immunologic effects of a pregnancy, we decided to examine the risk of NHL and CLL in relationship to full-term pregnancies. Within a nationwide cohort we identified 1,546 women with NHL and 198 women with CLL, all 15 years or older, born 1925-1972. Five age-matched controls were selected for each case patient. Conditional logistic regression was used to estimate the odds ratios after mutual adjustment for number of births and age at first birth. We found a weak, negative association between parity and risk of NHL (p for trend 0.11) and a transient, 10-40% decrease in risk within 5-14 years after the last birth among women with various parity status. The risk of CLL decreased more markedly, and orderly with increasing parity, but the trend was not significant (p = 0.18). Small numbers of cases with CLL prevented more detailed analyses of temporal relationships. Age at first birth appeared unrelated to the risk of both NHL and CLL. We conclude that the immunologic alterations associated with a pregnancy have limited, if any, relevance to the etiology of NHL and CLL; changing reproductive pattern is an unlikely contributor to the marked increase in incidence of NHL seen in many populations.

Adult↗

PubMed1997

Radiotherapy in addition to radical surgery in rectal cancer: evidence for a dose-response effect favoring preoperative treatment.

PURPOSE: This study explored the relationship between radiation dose and reduction in local recurrence rate after preoperative and postoperative radiotherapy in rectal cancer. METHODS AND MATERIALS: All randomized trials initiated prior to 1988 comparing preoperative and postoperative radiotherapy with surgery alone or with each other were included. Local failure rates were available in 5626 randomized patients. The linear quadratic formula was used to compensate for different radiotherapy schedules. RESULTS: For preoperative radiotherapy, a clear dose-response relationship could be established. For postoperative radiotherapy, the range of doses was narrow, and a dose-response relationship could not be demonstrated. At similar doses, preoperative radiotherapy appeared to be more efficient in reducing local failure rate than postoperative. The only trial comparing preoperative with postoperative radiotherapy confirms this notion. A 15-20 Gy higher dose may be required postoperatively than preoperatively to reach similar efficacy. Neither approach alone significantly influences survival, although it is likely that a small survival benefit may be seen after preoperative radiotherapy. CONCLUSIONS: The information from the entire randomized experience suggests that preoperative radiotherapy may be more dose efficient than postoperative radiotherapy.

Combined Modality Therapy↗

PubMed1997

Clinicopathological staging and management of colorectal cancer. Perioperative radiation therapy.

The use of radiotherapy, as a complementary procedure prior to surgery for immobile, nonresectable, rectal cancers or as an adjuvant treatment in patients with mobile rectal cancer is discussed. Locally nonresectable rectal cancer can be resected after prolonged preoperative radiotherapy. The proportion of patients possible to cure after this prolonged treatment is not precisely known, mainly due to differences in the criteria for nonresectability. Literature data show that between 35% and 80% can undergo resection for cure, and 25% to 40% can be long-term disease-free survivors. Moreover, the role of chemotherapy in combination with radiotherapy in this group is not yet settled owing to the lack of convincing data from randomized trials. Data from the literature clearly indicate that preoperative radiotherapy in patients with mobile rectal cancer is superior to postoperative irradiation. Provided the dose is sufficiently high, a relative reduction in the local recurrence rate of 60% in combination with "standard surgery" is to be expected, and this reduction increases long-term survival. An important question is the role of adjuvant radiotherapy together with "more optimized surgery." It is likely that the local recurrence rate will decrease with the same magnitude, indicating that local recurrent rectal cancer in patients with mobile rectal cancer can be more or less eradicated if optimized surgery is combined with preoperative radiotherapy. With proper timing and treatment technique, the adverse effects on surrounding tissues, both immediate and late, can be kept acceptably low.

Clinical Trials as Topic↗

PubMed1997

Short-term preoperative radiotherapy results in down-staging of rectal cancer: a study of 1316 patients.

BACKGROUND AND PURPOSE: This study was undertaken to investigate down-staging effects after short-term, high-fractionated preoperative radiotherapy. MATERIAL AND METHODS: The relationships between preoperative radiotherapy 25-25.5 Gy given over 5-7 days and clinical variables (sex, age, tumour level, metastatic disease, and tumour size) and the risk of lymph node metastases were examined in 1316 patients with rectal adenocarcinoma by uni-, and multivariate analyses. RESULTS: Irradiated specimens contained smaller tumours (P < 0.00001) and nodal metastases were less common (P < 0.001). In a logistic regression model, tumour size in cm was positively related to the risk for nodal spread (odds ratio, OR = 1.14, 95% confidence limits, CL, of OR 1.08-1.22). In the same model, radiotherapy decreased the risk for nodal involvement (OR 0.73, 95% CL 0.58-0.92. This risk was particularly reduced when the time interval between start of radiotherapy and surgery equalled 10 days or more. CONCLUSIONS: These results demonstrate a down-staging effect by a short course of preoperative radiotherapy which should be considered in the interpretation of radiotherapy trials and in the recruitment of patients for further postoperative adjuvant treatment.

Adenocarcinoma↗

PubMed1997

Potential advantages of protons over conventional radiation beams for paraspinal tumours.

BACKGROUND AND PURPOSE: Conformal treatment planning with megavoltage X-rays and protons was studied in an attempt to determine if there are advantage of boost therapy with protons instead of X-rays for a patient with a tumour growing around the cervical spinal cord. MATERIALS AND METHODS: A patient with a Ewing sarcoma was selected for the model study. The proton boost plan was realised with a six beam patched technique. Several X-ray boost techniques were planned, some not yet practically realisable. The techniques giving the best dose distributions and the best tumour control probabilities in the absence of significant late toxicity were looked for. The boost techniques were added to two large lateral X-ray beams covering the planning target volume (PTV) and the main risk organ, the spinal cord. The evaluation was made with two biological models, i.e. the tumour control probability (TCP) model, proposed by Webb and Nahum (Webb, S. and Nahum, A.E. A model for calculating tumour control probability in radiotherapy including the effect of inhomogeneous distributions of dose and clonogenic cell density. Phys. Med. Biol. 38: 653-666, 1993), and the normal tissue complication probability (NTCP) model, first derived by Lyman (Lyman, J.T. Complication probability as assessed from dose-volume histograms. Radiat. Res. 104: s13-s19, 1985). RESULTS: The comparison showed small but clear advantages of protons for the boost. At 1% NTCP in the spinal cord, the calculated TCP was on average 5% higher. However, depending on the values of the parameters chosen in the biological models, the gain for protons varied from 0-10%. The smallest gains were seen in radiosensitive tumours for which the TCP was close to 100% with any of the techniques and in radioresistant tumours for which neither technique resulted in any appreciable probability of local cure. CONCLUSION: Protons appear to have therapeutic advantages over conventional radiotherapy in tumours with relatively high radiosensitivity situated close to the spinal cord.

Adult↗

PubMed1997

The conceptual design of a radiation oncology planning system.

The conceptual design of a three-dimensional, radiation oncology planning system is described. To assure that clinical needs were met, the working routines in two major Swedish radiation oncology departments were analysed in detail. Generic work flow was identified and mapped and compared to those in other institutions. The flow was partitioned into a number of nodes that together formed a basis for the design of the system handling logistics. The design criteria of this system emphasised accommodation of current clinical practice and traditional treatment modalities, and facilitated means to validate the computational techniques. The system should also allow for new procedures and was based on the analysis of current practice and a synthetic idea of how 3D treatment planning should be done. The final product supports the treatment planning work in its entirety. It is believed that the techniques followed are of interest to those engaged in computer systems of similar purposes and complexities.

Computer Systems↗