Biomedical subjects

R Swindell

Publications and source records attributed to R Swindell.

At least 55 records · Page 3Linked to original sources

PubMed1999

Lack of correlation between residual radiation-induced DNA damage, in keratinocytes assayed directly from skin, and late radiotherapy reactions in breast cancer patients.

PURPOSE: To study the relationship between the severity of late reactions to radiotherapy in breast cancer patients, and the extent of residual radiation-induced DNA damage, using a rapid assay of keratinocytes obtained directly from skin biopsies. METHODS AND MATERIALS: A review was made of 32 patients with breast cancer, treated uniformly by radiotherapy between 1983 and 1988, following breast-conserving surgery. Their late radiotherapy reactions were scored (9-14 years post-radiotherapy) using a modified LENT SOMA scale, and a 5-mm buttock skin punch biopsy was obtained. Intact skin was irradiated at room temperature, and after allowing 24 h for repair, the tissue was disaggregated and the cells processed for pulsed field gel electrophoresis (PFGE). Residual DNA damage was expressed as the fraction of DNA released (FDR) following 150 Gy. RESULTS: Studies using flow cytometry on disaggregated breast skin showed that over 90% of the cells were keratinocytes. The PFGE assay was robust with low background FDRs in unirradiated skin samples (mean 3.2%) and a wide range of FDRs following irradiation from 11.5% to 26.6%. No correlation was found between the FDR at 150 Gy (FDR 150) and any of the late reaction scores or retrospective acute reaction scores. There was, however, a borderline significant correlation for family history and FDR 150 (p = 0.059). CONCLUSION: Rapid measurement of residual DNA damage in irradiated differentiated keratinocytes, the predominant cell population in skin biopsies, showed no correlation with the severity of symptomatic early or documented late reactions in a retrospectively studied group of 32 breast cancer patients.

Adult↗

PubMed1999

A correlation between residual radiation-induced DNA double-strand breaks in cultured fibroblasts and late radiotherapy reactions in breast cancer patients.

BACKGROUND AND PURPOSE: Prediction of late normal tissue reactions to radiotherapy would permit tailoring of dosage to each patient. Measurement of residual DNA double strand breaks using pulsed field gel electrophoresis (PFGE) shows promise in this field. The aim of this study was to test the predictive potential of PFGE in a group of retrospectively studied breast cancer patients. MATERIALS AND METHODS: Thirty nine patients, treated uniformly for breast cancer 9-15 years previously, with excision of the tumour and radiotherapy to the breast and drainage areas, were assessed clinically using the LENT SOMA scale, and a 5-mm punch biopsy taken from the buttock. Fibroblast cell strains were established and used to study residual DNA double strand breaks, using PFGE. RESULTS: There were significant correlations between the DNA assay results and the fibrosis score (r(s) = 0.46; P = 0.003), the combined fibrosis and retraction score (r(s) = 0.45, P = 0.004) and the overall LENT score (r(s) = 0.43; P = 0.006). Using polychotomous logistic regression, the fibroblast DNA assay result was an independent prognostic factor for fibrosis severity. CONCLUSIONS: There is a relationship between residual radiation-induced DNA damage in fibroblasts and the severity of the late normal tissue damage seen in the patients from whom the cells were cultured.

Breast Neoplasms↗

PubMed1999

Definitive radiotherapy for 114 cases of T3N0 glottic carcinoma: influence of dose-volume parameters on outcome.

BACKGROUND AND PURPOSE: Assuming that the dose-response curve for T3N0M0 glottic carcinoma is steep and that the rate of occult lymph node metastases is low, it should be possible to employ high biological tumour doses to modest target volumes and thereby maximise laryngeal control without compromising final neck control. Within the constraints of a retrospective study we aim to examine this policy with respect to local control, incidence of nodal relapse and late complications. MATERIALS AND METHODS: One hundred and fourteen patients with T3N0M0 glottic carcinoma who received a 3-week schedule of radical radiotherapy between 1986 and 1994 were analysed. The median age was 67 years (range, 34-85 years) and the median follow-up for living patients was 4.8 years (1.9-8.9 years). There were no strict selection criteria for those patients treated with radiotherapy. RESULTS: The 5-year overall survival was 54%. The 5-year local control with radiotherapy and the ultimate loco-regional control following salvage laryngectomy were 68 and 80%, respectively. Nine patients (8%) suffered a regional nodal relapse but only three of these (3% overall) occurred in the absence of local failure. Four patients (3.5%) developed serious late complications requiring surgical intervention (three received 55 Gy and one 52.5 Gy). CONCLUSIONS: It is possible to employ maximum tolerable doses to specific target volumes and thereby exploit the dose response demonstrated and minimise major late effects. The use of modest target volumes resulted in only 3% of patients requiring surgery that might have been avoided had prophylactic neck irradiation been employed.

Adult↗

PubMed1999

The diagnostic value of positron emission tomography (PET) with radiolabelled fluorodeoxyglucose (18F-FDG) in head and neck cancer.

Positron emission tomography (PET) scanning has recently been introduced into clinical practice but its usefulness in the management of head and neck cancer is not well defined. The aim of this prospective preliminary study was to examine the clinical value of fluorodeoxyglucose (FDG)--PET in patients with head and neck cancer treated by radiotherapy with surgery in reserve by (i) relating quantitative uptake of isotope to tumour type and histological grade and (ii) comparing the imaging findings of PET and magnetic resonance imaging (MRI) in post-radiotherapy assessment of tumour response. Twenty-one patients had pre-treatment PET and MRI scans and these were repeated four and eight months after treatment if there was no clinical relapse. Pre-treatment uptake of FDG using tumour to cerebellar ratio parameters was significantly related to the histological grade of squamous cancer (p = 0.04) but not to tumour type. Discordance of post-treatment PET/MRI findings in one case indicates a possible role for PET in the early detection of tumour recurrence. Other potential uses of PET scanning in the management of head and neck cancer are discussed.

Adult↗

PubMed1999

Outcome of radiotherapy after breast conserving surgery in screen detected breast cancers.

The treatment outcomes were reviewed for all the patients at this institute who underwent breast irradiation after breast conserving surgery in 1991. Of a total of 643 patients treated, 194 (30%) had presented with tumours detected by screening mammography. The breast was irradiated with a tangential pair of fields, giving a dose of 40 Gy in 15 fractions over 3 weeks in 97% of these patients. A boost was not used. With a median follow-up of 4.7 years, there was better cancer related survival in patients with screen detected cancers compared with those that were non-screen detected (94% versus 84% at 5 years; P = 0.002). The breast recurrence rate at 5 years was 1% for screen detected cancers compared with 6% for those that were non-screen detected (P = 0.01). Factors additional to screen detected status that were found to be significant for cancer survival were pathological stage (P = 0.03) and histological grade (P = 0.01). In a Cox multivariate analysis, only two factors were significant for breast recurrence: screen detected status (P = 0.023) and histological grade (P = 0.016). This study suggests that breast irradiation with 40 Gy given over 3 weeks after breast conserving surgery for screen detected breast cancer gives a high level of local control out to 5 years.

Aged↗

PubMed1998

Epithelial proliferation and hormone receptor status in the normal post-menopausal breast and the effects of hormone replacement therapy.

The proliferation rate (as assessed by Ki67 expression) and expression of oestrogen-regulated progesterone receptor (PR) was studied in normal post-menopausal breast epithelium. Normal breast epithelium from patients receiving hormone replacement therapy (HRT) at the time of surgery containing either oestrogen alone (E2) or oestrogen and progesterone combined activities (E2 + P) was also studied, as HRT has been linked to an increased breast cancer risk. Samples of breast tissue, containing normal epithelium, from 185 patients undergoing surgery for benign or malignant disease were immunocytochemically stained for PR and Ki67. The percentage of labelled cells was expressed as the labelling index (LI). The median Ki67 LI in normal post-menopausal breast epithelium was 0.19 and median PR LI was 4.75, and both were unaffected by patient age, duration of menopause or if the tissue sample originated from a breast with benign or malignant disease. Proliferation did not alter significantly in patients taking HRT (P = 0.61); however, PR expression was up-regulated in both E2 and E2 + P users (P = 0.01). The dose and duration of HRT had no effect on either parameter. A possible attenuation of sensitivity to oestradiol-induced proliferation but not to PR expression occurs in the post-menopausal breast.

Aged↗

PubMed1998

The intrinsic radiosensitivity of normal and tumour cells.

PURPOSE: To examine whether in vitro measurements of normal and tumour cell radiosensitivity can be used as prognostic factors in clinical oncology. MATERIALS AND METHODS: Stage I-III cervix carcinoma patients were treated with radical radiotherapy with a minimum of 3 years' follow-up. Lymphocyte and tumour radiosensitivities were assayed using, respectively, a limiting dilution and soft agar clonogenic assay to obtain surviving fraction at 2 Gy (SF2). The results were related, in an actuarial analysis, to late morbidity assessed using the Franco Italian glossary. RESULTS: Patients with radiosensitive lymphocytes had a significantly increased risk of developing late complications (n = 93, p = 0.002). Increasing tumour radiosensitivity was associated with an increased risk of morbidity (n= 113, p=0.032). A significant correlation was found between fibroblast and tumour cell radiosensitivity (r=0.57, p=0.03), but a weak inverse association was found between lymphocyte and tumour cell radiosensitivity (r= -0.32, p=0.03). Patients with radiosensitive lymphocytes and tumour cells had higher levels of late complications than those whose cells were radioresistant. CONCLUSION: The work described highlights the importance of cellular radiosensitivity as a parameter determining the clinical response to radiotherapy.

Carcinoma↗

PubMed1997

Bladder movement during radiation therapy for bladder cancer: implications for treatment planning.

PURPOSE: To describe and quantify bladder movement during radical radiation therapy (RT). To attempt to identify factors that predict for excessive alterations in bladder position. To use the above information to assist in defining the "adequate" planning target volume margin. METHODS AND MATERIALS: Thirty patients with bladder cancer suitable for radical courses of RT were followed prospectively. Patients had an initial planning computerized tomography (CT) scan of the pelvis and three subsequent scans performed weekly during the treatment period. The following measurements were made on each scan in the midbladder slice: maximum anteroposterior (AP) and lateral bladder dimensions, AP rectal diameter, and the distance (margin) between the bladder walls (anterior, posterior, right, and left lateral) and the 95% isodose line. Various patient and tumor data, including bladder and bowel symptoms, were recorded to attempt correlation with bladder movement. RESULTS: Bladder size: the median bladder size (area) over all scans in all patients was 36.9 cm2 (range: 16.2 to 80.9 cm2). The change in bladder area across each sequence varied from 3.3 to 29.1 cm2 (7-55% change in area between scans). Patients with bladders of larger than the median size on the planning scan (despite emptying) were more likely to have alteration in size than those with small bladders, and this change was in the direction of contraction (p = 0.01). Bladder displacement: bladder wall movement of > 1.5 cm was defined as "significant." Eighteen of 30 patients (60%) demonstrated "significant" movement of at least one bladder wall relative to the original isodose plot. Movement resulting in margin reduction occurred in 10 patients (33%). Two patients required treatment replanning due to consistently altered bladder position. There was no pattern to displacement through RT, and all walls were at approximately equal risk of movement. Factors influencing bladder movement: posterior bladder wall movement appeared to relate to "marked" (>2 cm) rectal diameter change. There was a trend for patients with larger amounts of residual bladder tumor (greater than the median) to exhibit more bladder movement; 11 of 14 "moved" compared with 7 of 16 patients with less residual tumor. Other clinical factors including age, sex, body size, acute RT reaction, and tumor stage did not appear to relate to bladder movement. CONCLUSION: Bladder movement during RT is clinically relevant and is random with respect to both time and direction. We recommend, at least with respect to tumor-bearing regions of the bladder, that no less than a 2.0 cm margin should be allowed.

Aged↗

PubMed1996

Prognostic factors for breast recurrence after conservative breast surgery and radiotherapy: results from a randomised trial.

Prognostic factors predicting for breast recurrence following breast conserving surgery and radiotherapy have been identified in a prospective randomised trial comparing two different radiotherapy techniques. The first used megavoltage radiation to encompass the whole breast and regional nodes (WF group). The second used an electron field directed to the tumour bed only (LF group). With a median follow up of 8 years survival in both groups was the same (72%). There was an increased rate of breast recurrence in the LF group: 25%, compared to the WF group: 13% (P = 0.00008), expressed in actuarial terms at 8 years. In a multivariate analysis of factors predicting for breast recurrence, once the difference in treatment technique is allowed for, only two factors were found to be significant: histological grade (P = 0.013) and lymphovascular invasion in the histological specimen (P = 0.037).

Breast Neoplasms↗

PubMed1996

Radical external beam radiotherapy for 333 squamous carcinomas of the oral cavity--evaluation of late morbidity and a watch policy for the clinically negative neck.

BACKGROUND AND PURPOSE: The aims of this study were to examine local control/morbidity for all cases and a 'watch policy' for the node-negative neck. PATIENTS/METHODS: 333 patients with squamous cell carcinoma of the oral cavity were treated with a short radical radiotherapy regime to the primary site and involved lymph node groups at the Christie Hospital, Manchester, between 1980 and 1987. Only 10 of 278 node-negative patients received elective neck node irradiation. RESULTS: Actuarial cancer-free survival and local control rates at 5 years for the whole group were 55% and 61%, respectively. Control at the primary site was adversely related to increasing T-stage, node positivity and bone involvement at presentation. Osteonecrosis was seen in 14 (5.9%) of 237 cases without bone involvement at presentation. Taking all patients, late morbidity (non-healing soft tissue injury or bone necrosis) was seen in 45 patients (13.6%) at a median time of 21 months from treatment. The factors contributing to late morbidity were: (1) bone involvement at presentation, (2) synchronous MTX chemotherapy, (3) the contribution of scattered radiation from elective neck treatment, (4) increasing radiation dose, (5) increasing target volume for doses less than 55 Gy and (6) dental extractions. Eighty-four (31%) patients who were initially node-negative developed disease in the untreated neck during follow-up. Salvage neck dissections controlled neck disease in half of the node-only recurrences (21/42 cases). CONCLUSION: These results have influenced our treatment policy, with lowering of the primary tumour dose in some cases and addition of elective neck irradiation for T2-T4 No patients.

Antimetabolites, Antineoplastic↗

PubMed1996

Mobilisation kinetics of primitive haemopoietic cells following G-CSF with or without chemotherapy for advanced breast cancer.

BACKGROUND: The objective of this study was to determine the optimal conditions for blood progenitor cell harvest for transplantation, with main emphasis on the mobilisation kinetics of primitive, marrow repopulating cells. PATIENTS AND METHODS: Sixteen patients with advanced breast cancer were treated with 4 cycles of dose escalating FAC chemotherapy (5-fluorouracil, adriamycin, cyclophosphamide) each followed by 10 micrograms/kg/d G-CSF for 13 days. We assessed the number of colony-forming cells (CFC), and estimated the long-term culture initiating cells (LTC-IC) and CD34+ cells during the recovery phase of cycle 1 and 4 of chemotherapy, and during additional periods of G-CSF administration either preceding or following the full course of chemotherapy. RESULTS: The highest peak numbers of CFC per ml of blood (median 10489, range 860-39282) were mobilised after the first cycle of chemotherapy. The lowest peak numbers of CFC were obtained during the recovery phase from cycle 4 (median 4739, range 40-26789). In contrast, the numbers of CD34+ cells per ml of blood were significantly higher in cycle 4 (median 650, range 30-2600 x 10(2)) compared to those of cycle 1 (median 240, range 20-770 x 10(2)). The peak numbers of CFC mobilised by G-CSF before commencement and after the cessation of chemotherapy were equivalent, with a median of 5470 (range 1056-25669) and 5948 (range 2710-38975) per ml of blood, respectively. However, while mononuclear cells (MNC) collected at the days of maximal CFC mobilization following G-CSF administration before or after cycle 1 were similar to normal bone marrow MNCs in their ability to generate haemopoiesis when seeded onto performed irradiated stroma, those collected after cycle 4 or during G-CSF administration after the cessation of chemotherapy were markedly compromised in this respect. CONCLUSIONS: Our results indicate that repeated cycles of FAC chemotherapy followed by G-CSF result in a far lower number of LTC-IC than of CFC mobilised into the circulation. Furthermore although the combination of chemotherapy and G-CSF mobilised the highest numbers if CFC, G-CSF alone pre-chemotherapy was more effective at mobilising LTC-IC. These data indicate that neither the numbers of CFC mobilised nor the numbers of CD34+ cells are necessarily a reliable indicator for the putative marrow repopulating capability of the blood cells mobilised with chemotherapy plus G-CSF.

Adult↗

PubMed1996

A randomised trial investigating the dose intensity of primary chemotherapy in patients with ovarian carcinoma: a comparison of chemotherapy given every four weeks with the same chemotherapy given at three week intervals.

BACKGROUND: The dose intensity of chemotherapy for patients with ovarian carcinoma remains a controversial issue. Few randomised trials have been conducted examining dose intensity using the same total dose of chemotherapy. This study was designed to investigate two schedules of chemotherapy using standard and higher dose intensity with both groups receiving the same total dose. PATIENTS AND METHODS: Patients with FIGO stage IC, II, III and IV epithelial ovarian carcinoma were randomised to receive cycles of cyclophosphamide (600 mg/m2) and carboplatin (300 mg/m2) alternating with doxorubicin (50 mg/ m2) and ifosfamide (5 g/m2) at either four-weekly (n = 47) or three-weekly (n = 97) intervals (1:2 randomisation). At randomisation patients were stratified according to histological grade and amount of post operative residual tumour (greater or less than 2 cm). The two arms of the study were well balanced in terms of the major prognostic features. RESULTS: There was no difference in either progression free survival or overall survival between the two arms. The median overall survival was 730 days for the three-weekly treatment and 740 days in the four-weekly arm (progression-free survival was 500 days and 483 days, respectively). The combined overall response rate (complete and partial response) in the 114 assessable patients was 65.7% (66.7% for the three-weekly treatment and 64% for the four-weekly treatment). These differences were not statistically different. CONCLUSIONS: A modest increase in the dose intensity of chemotherapy (1:3 fold) failed to improve the response rate, progression-free survival and overall survival in patients with ovarian carcinoma.

Adult↗

PubMed1995

Effect of growth hormone replacement on bone mass in adults with adult onset growth hormone deficiency.

OBJECTIVE: Previous studies of the effect of GH replacement on bone mass in adults with GH deficiency have produced conflicting results. We have studied the effect of 6 and 12 months of GH replacement on bone mass in adults with adult onset GH deficiency. DESIGN: Double blind placebo controlled study of GH replacement (0.125 IU/kg/week for the first month and 0.25 IU/kg/week thereafter) for 6 months and an open study for a further 6 or 12 months. PATIENTS: Twenty-two adults (10 men, 12 women), aged 41.5 +/- 2.1 years (mean +/- SE, range 23.6-59.5), with adult onset GH deficiency. MEASUREMENTS: Single-energy quantitative computed tomography was used to measure vertebral trabecular bone mineral density (BMD), single-photon absorptiometry (SPA) was used to measure forearm cortical and integral bone mineral content and BMD and dual-energy X-ray absorptiometry (DXA) was used to measure lumbar spine, femoral neck, trochanteric and Ward's triangle integral BMD. RESULTS: After 6 months of GH replacement (n = 21) there was a significant decrease in forearm cortical BMD (SPA: median change -0.009 g/cm2, P = 0.01), forearm integral BMD (SPA: median change -0.016 g/cm2, P = 0.03), lumbar spine BMD (DXA: median change -0.22 g/cm2; P = 0.003) and femoral neck BMD (DXA: median change -0.029 g/cm2, P = 0.006). After 12 months of GH replacement (n = 13) there was a significant decrease in lumbar spine BMD (DXA: median change -0.035 g/cm2, P = 0.002) from baseline. There was no significant increase in bone mass at any site after 6 or 12 months of GH replacement. Change in bone mass was not influenced by sex of the patient or by presence or absence of additional pituitary hormone deficiencies. CONCLUSION: The response of bone mass to 6 and 12 months of GH replacement in adults with adult onset GH deficiency is disappointing. Longer-term studies are required to determine whether prolonged GH replacement has a beneficial effect on bone mass.

Adult↗

PubMed1995

Gonadal function following chemotherapy for Hodgkin's disease: a comparative study of MVPP and a seven-drug hybrid regimen.

PURPOSE AND METHODS: Gonadal function was assessed in 89 patients after chemotherapy for Hodgkin's disease (HD). Thirty-seven patients had received mechlorethamine, vinblastine, prednisolone, and procarbazine (MVPP) and 52 patients, a hybrid combination of chlorambucil, vinblastine, prednisolone, procarbazine, doxorubicin, vincristine, and etoposide (ChIVPP/EVA). Fifty men (MVPP, n = 21; ChIVPP/EVA, n = 29) with a median age of 26 years (range, 16 to 54) and 39 women (MVPP, n = 16; ChIVPP/EVA, n = 23) with a median age of 30 years (range, 15 to 47) were studied at a median of 30 months (range, 4 to 83) following chemotherapy. RESULTS: Semen analysis showed azoospermia in 35 of 37 men, and increased serum follicle-stimulating hormone (FSH) levels in this group confirmed severe germinal epithelial damage. Analysis of pretreatment semen in 28 men showed azoospermia in one, oligospermia in four (sperm count < 20 x 10(6)/mL), and a normal sperm count in the remaining 23. In the women, 26 of 34 (76%) with a regular menstrual cycle before commencing chemotherapy became amenorrheic following treatment. Menses returned in 10 women, who had a median age of 25 years (range, 21 to 34), and there were two pregnancies in this group. In the other 16, with a median age of 36 years (range, 27 to 47), amenorrhea persisted and premature ovarian failure was confirmed by increased serum gonadotrophins and reduced estradiol (E2) concentrations. Of the original eight women in whom menses were maintained following treatment, two subsequently developed amenorrhea and the clinical and biochemical features of an early menopause. In total, 18 of 34 women (53%) required hormone replacement therapy for chemotherapy-induced ovarian failure. CONCLUSION: There was no statistically significant difference in the frequency or severity of gonadal dysfunction between MVPP- and ChIVPP/EVA-treated patients. We conclude that both of these chemotherapy schedules cause substantial damage to gonadal function in both sexes.

Adolescent↗

PubMed1995

Clinical and in vitro effects of recombinant human erythropoietin in patients receiving intensive chemotherapy for small-cell lung cancer.

PURPOSE: Recombinant human erythropoietin (r-Hu-EPO) is known to be effective in untreated cancer patients. Here we assess the possibility that r-Hu-EPO may also prevent or reduce anemia in patients who receive cytotoxic chemotherapy. METHODS: Thirty-six patients with small-cell lung carcinoma (SCLC) were enrolled onto a three-arm, randomized trial to investigate the effect of r-Hu-EPO on hemoglobin (Hb) levels and RBC and platelet (Plt) transfusions during chemotherapy. Bone marrow progenitors were studied before and after treatment. Two groups of patients received r-Hu-EPO at a dose of either 150 IU/kg (group 150) or 300 IU/kg (group 300) three times per week for the duration of chemotherapy. A control group did not receive r-Hu-EPO (group O). A maximum of six cycles of a chemotherapy regimen that consisted of vincristine, ifosfamide, carboplatin, and etoposide (VICE) were given to all patients. Hematologic parameters were measured weekly, and RBC or Plt transfusions were given for Hb levels less than 9 g/dL and Plt counts less than 20 x 10(9)/L. RESULTS: Hb levels decreased in all patients, but onset of anemia was delayed in groups that received r-Hu-EPO (P = .002). A total of 116 U RBC were transfused in group 0, 54 in group 150, and 52 in group 300 (P = .017). In addition, there was a nonsignificant trend toward higher Plt counts and fewer Plt transfusions in patients who received r-Hu-EPO. CONCLUSION: r-Hu-EPO at a dose of either 150 or 300 IU/kg three times weekly delays the onset of anemia and reduces RBC transfusion requirements in patients who undergo intensive chemotherapy for SCLC. A possible effect of r-Hu-EPO on platelet numbers deserves further study.

Adult↗

PubMed1994

Weekly VAPEC-B chemotherapy for high grade non-Hodgkin's lymphoma: results of treatment in 184 patients.

UNLABELLED: BACKGROUND AND PATIENTS: A weekly schedule of chemotherapy (VAPEC-B) has been used to treat 184 consecutive patients with high grade non-Hodgkin's lymphoma (NHL). Median age for the group was 57 years (range 17-84) and 56% had stage IV disease. RESULTS: Following chemotherapy, 114 (62%) patients achieved CR or CR(u), 32 (17%) PR and 15 (8%) had not responded or progressed. Response to VAPEC-B was highly stage dependent with 70% or more of patients with stages I-III achieving CR or CR(u) but only 50% of those with stage IV. Twenty-four (15%) patients died during treatment with VAPEC-B and in 13 cases death was due to sepsis. This complication occurred mainly in patients with stage IV disease aged 60 years or older. After a median follow up period of 4.1 years, the actuarial 4 year survival for 184 patients is 45%, an overall result heavily influenced by the poor outcome for 103 patients with stage IV disease (4 year survival of 28%). Patients with earlier stage disease fared correspondingly better (44% for stage III, 68% for stage II and 80% for stage I). CONCLUSIONS: VAPEC-B gives similar results to other chemotherapy regimens currently used in the treatment of high grade NHL and has the advantage of brevity. Caution is advised in patients over the age of 60 especially in the presence of stage IV disease and dose reduction or haemopoietic growth factor support should be considered in these circumstances.

Adolescent↗

PubMed1993

Transplantation potential of hematopoietic cells released into the circulation during routine chemotherapy for non-Hodgkin's lymphoma.

Primitive hematopoietic cells released into the peripheral blood (PB) were studied in 50 patients with high-grade non-Hodgkin's lymphoma enrolled in a phase III trial of intensive weekly chemotherapy (VAPEC-B) alone or with granulocyte colony-stimulating factor (G-CSF). Mononuclear cells numbers were monitored and their in vitro growth potential assessed in clonogenic progenitor cell assays and in long-term culture. Total colony-forming cells (granulocyte-macrophage [GM], burst-forming unit, erythroid [BFU-E], Mix-CFC) were increased 40-fold (median) over baseline with chemotherapy alone and 106-fold with chemotherapy and G-CSF after the final dose. CD34+ cells were increased to a median of 4%, equivalent to that in normal bone marrow (BM) controls. Circulating colony-forming cell levels were maximal when the recovering total white blood cell (WBC) count reached 5 to 10 x 10(9)/L. The timing of the maximum was reproducible in individual patients. Therefore the WBC count can be used as a guide to the timing of leukapheresis. PB cells from normal controls' and patients' prechemotherapy were unable to sustain hemopoiesis in two-stage long-term cultures. In contrast, PB cells collected from patients primed with chemotherapy alone or chemotherapy with G-CSF at the time of predicted maximal colony-forming cell release were able to generate and sustain hematopoiesis in long-term cultures at a level comparable or superior to normal BM. These findings indicate that the use of G-CSF after routine outpatient chemotherapy stimulates maximal release of primitive hemopoietic cells into the circulation, including colony-forming cells and long-term culture-initiating cells. Their numbers are comparable with those in normal BM and are such that a single leukapheresis will usually yield enough cells for hemopoietic reconstitution after myeloablative chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1993

The Christie Hospital breast conservation trial: an update at 8 years from inception.

In 1990, we published the results of a clinical trial involving 708 patients with breast carcinoma of 4 cm or less in diameter, who, following lumpectomy, were randomized to have radiotherapy to the tumour bed only (limited field, LF group) or to the whole breast and regional nodes (wide field, WF group). No adjuvant systemic therapy was prescribed. At the time the median follow-up was 37 months. We present the updated results after an extended median follow-up of 65 months. The overall survival is 72.7% and 71.2% for the LF and WF groups respectively. The actuarial breast recurrence rate (first event) is 15% (LF) versus 11% (WF) for infiltrating ductal carcinoma, whereas, for infiltrating lobular carcinoma, the recurrence rate was 34% (LF) versus 8% (WF). A high actual recurrence rate of 21% (LF) and 14% (WF) was also found for extensive ductal carcinoma in situ. It was extremely rare for medullary, mucoid or tubular carcinomas to recur. Salvage surgery was possible in 86% (LF) and 90% (WF) respectively. The recurrence rate in the breast following lumpectomy and wide field irradiation is comparable with others reported in the literature. This trial also shows the lumpectomy with limited field irradiation is feasible, albeit with a higher breast recurrence rate; the latter could be reduced by improved selection and refinement of the technique.

Aged↗