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Biomedical subjects

H Anderson

Publications and source records attributed to H Anderson.

At least 19 recordsLinked to original sources
PubMed2006

Histopathological risk factors for ipsilateral breast events after breast conserving treatment for ductal carcinoma in situ of the breast--results from the Swedish randomised trial.

AIM: The primary aims were to study risk factors for an ipsilateral breast event (IBE) after sector resection for ductal carcinoma in situ of the breast (DCIS) in a trial comparing adjuvant radiotherapy to no therapy and to assess predictive factors for response to radiotherapy. Secondary aims were to analyse reproducibility of the histopathological evaluation and to estimate correctness of diagnosis in the trial. SETTING: A randomised trial in Sweden (the SweDCIS trial), including 1046 women with a median of 5.2 years of follow-up in a population, offered routine mammographic screening. METHODS: A case-cohort design with a total of 161 cases of IBE (42 of those being members of the subcohort) and 284 sampled for the sub-cohort. Ninety five percent of the participants' slides could be retrieved and were re-evaluated by three experienced pathologists. RESULTS: Low nuclear grade (NG 1-2) and absence of necrosis halves the risk of IBE in both irradiated and non-irradiated patients. Lesion size, margins of excision and age at diagnosis did not modify these associations. The presence of necrosis modified the effect of radiotherapy: relative risk was 0.40 with necrosis present and 0.07 with necrosis absent (p-value for interaction 0.068). In all subsets of prognostic factors, radiotherapy conferred a substantial benefit. The risk factors for in situ and invasive IBE were similar. The agreement between pathologists was moderate (kappa=0.486). Correctness of diagnosis in the subcohort of SweDCIS was 84.8%. CONCLUSION: Although nuclear grade and necrosis carry prognostic information, we could not define a group with very low risk after sector resection alone. Radiotherapy has a protective effect in all substrata of risk factors studied. The interaction between the presence of necrosis and radiotherapy is a clinically and biologically relevant research area.

Breast Neoplasms↗
PubMed2006

High leucovorin doses during high-dose methotrexate treatment may reduce the cure rate in childhood acute lymphoblastic leukemia.

We explored the relationship between time to relapse and different exposure variables (serum methotrexate (S-MTX) 23, 36 and 42 h after start of administration, MTX elimination time and leucovorin (LV) dose) during high-dose MTX (HDM) treatment of 445 children with acute lymphoblastic leukemia. MTX was infused at 5 g/m2 (non-high risk) or 8 g/m2 (high risk) over 24 h, 2-9 times per patient. LV rescue dose was adjusted according to the S-MTX concentration. Time from end of the last HDM to relapse was analyzed by Cox regression analysis with the logarithms of S-MTX and LV dose as exposures. The combined results from all risk groups suggest that high LV dose is related to higher risk for relapse. Doubling of the LV dose increased the relapse risk by 22% (95% confidence interval 1-49%, P = 0.037). High LV doses correlated with high MTX levels at 23, 36 and 42 h and longer elimination time. The results suggest that high doses of LV increase the risk for relapse despite the fact that they were correlated with high MTX levels and longer MTX elimination time. The choice of MTX and LV doses may be regarded as an intricate balance between effect and counter-effect.

Antimetabolites, Antineoplastic↗
PubMed2006

Phase II study of SPI-77 (sterically stabilised liposomal cisplatin) in advanced non-small-cell lung cancer.

To determine the efficacy and tolerability of SPI-77 (sterically stabilised liposomal cisplatin) at three dose levels in patients with advanced non-small-cell lung cancer (NSCLC). Patients had Stage IIIB or IV NSCLC and were chemo-naïve, and Eastern Oncology Cooperative Group 0-2. The first cohort received SPI-77 at 100 mg m-2, the second 200 mg m-2 and the final cohort 260 mg m-2. Patients had also pharmacokinetics and analysis of leucocyte platinum (Pt)-DNA adducts performed. Twenty-six patients were treated, with 22 patients being evaluable for response. Only one response occurred at the 200 mg m-2 dose level for an overall response rate of 4.5% (7.1% at >or=200 mg m-2). No significant toxicity was noted including nephrotoxicity or ototoxicity aside from two patients with Grade 3 nausea. No routine antiemetics or hydration was used. The pharmacokinetic profile of SPI-77 was typical for a liposomally formulated drug, and the AUC appeared to be proportional to the dose of SPI-77. Plasma Pt levels and leucocyte DNA adduct levels did not appear to rise with successive doses. SPI-77 demonstrates only modest activity in patients with NSCLC.

Aged↗
PubMed2006

Management of a syphilis outbreak in street sex workers in east London.

OBJECTIVE: To describe the control and management of a syphilis outbreak in female street sex workers (SSWs) in east London. METHODS: Following the identification of several cases of infectious syphilis in SSWs in east London, a targeted service for screening and treatment of syphilis and other sexually transmitted infections was developed. A multidisciplinary team (MDT) joined an existing outreach service to facilitate this. Once it became apparent that this was not an isolated case, an outbreak control team (OCT) was established. RESULTS: Between April and December 2004 a total of 14 (58%) women with 15 cases of infectious syphilis were identified in 24 SSWs: 14/15 (93%) received treatment. Epidemiological treatment for syphilis was also given to the rest of SSWs at the initial visit. Several coexistent STIs were identified in this cohort. As part of the enhanced outbreak surveillance in north east London, 21 cases of infectious syphilis were reported in SSWs between April 2004 and December 2005. CONCLUSION: Outbreak management in this population was challenging: an MDT approach was crucial in identifying and treating syphilis to prevent onward transmission. There was a high prevalence of syphilis and other STIs in this cohort, and we treated the majority of cases. The formation of an OCT enabled us to monitor the outbreak and implement control measures more effectively. The novel intervention we describe has proved valuable in helping to control this syphilis outbreak.

Cohort Studies↗
PubMed2006

A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1).

BACKGROUND: Phase III studies suggest that non-small-cell lung cancer (NSCLC) patients treated with cisplatin-docetaxel may have higher response rates and better survival compared with other platinum-based regimens. We report the final results of a randomised phase III study of docetaxel and carboplatin versus MIC or MVP in patients with advanced NSCLC. PATIENTS AND METHODS: Patients with biopsy proven stage III-IV NSCLC not suitable for curative surgery or radiotherapy were randomised to receive four cycles of either DCb (docetaxel 75 mg/m(2), carboplatin AUC 6), or MIC/MVP (mitomycin 6 mg/m(2), ifosfamide 3 g/m(2) and cisplatin 50 mg/m(2) or mitomycin 6 mg/m(2), vinblastine 6 mg/m(2) and cisplatin 50 mg/m(2), respectively), 3 weekly. The primary end point was survival, secondary end points included response rates, toxicity and quality of life. RESULTS: The median follow-up was 17.4 months. Overall response rate was 32% for both arms (partial response = 31%, complete response = 1%); 32% of MIC/MVP and 26% of DCb patients had stable disease. One-year survival was 39% and 35% for DCb and MIC/MVP, respectively. Two-year survival was 13% with both arms. Grade 3/4 neutropenia (74% versus 43%, P < 0.005), infection (18% versus 9%, P = 0.01) and mucositis (5% versus 1%, P = 0.02) were more common with DCb than MIC/MVP. The MIC/MVP arm had significant worsening in overall EORTC score and global health status whereas the DCb arm showed no significant change. CONCLUSIONS: The combination of DCb had similar efficacy to MIC/MVP but quality of life was better maintained.

Adult↗
PubMed2005

Randomized phase II study of two gemcitabine schedules for patients with impaired performance status (Karnofsky performance status </= 70) and advanced non-small-cell lung cancer.

PURPOSE: This randomized phase II study compared two treatment schedules of gemcitabine in patients with non-small-cell lung cancer (NSCLC) and impaired Karnofsky performance status (KP). Primary objectives were to record changes from baseline KP and to assess symptom palliation. Secondary objectives were overall survival, tumor response, and toxicity. PATIENTS AND METHODS: Patients with stage IIIb and IV NSCLC and KP </= 70 were randomly assigned to receive gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 of each 28-day cycle (3w4) or gemcitabine 1,500 mg/m(2) on days 1 and 8 of each 21-day cycle (2w3), both for up to six cycles. KP, toxicity, and SS14 lung cancer specific questions were recorded before each cycle of treatment. Response was evaluated 4 weeks after the last cycle. RESULTS: One hundred seventy-four patients were enrolled. There was significant early attrition due to disease progression; only 61.5% of patients were alive at 2 months. There was a significant improvement in KP from baseline to pre-cycle 3 in both arms, with a trend in favor of the 3w4 regimen for duration and faster onset of improvement. Eight of the 17 quality-of-life (QOL) variables assessed showed an improvement of more than 10% between baseline and the start of the third cycle of treatment. Response rate, survival, and duration were similar in both arms. CONCLUSION: There was no significant difference between the two schedules examined in terms of improvement in KP or QOL, but there seemed to be a trend in favor of the 3w4 schedule.

Adult↗
PubMed2005

Breech presentation: an audit project as means of pursuing clinical excellence.

Clinical audit is an effective quality improvement process to evaluate important clinical issues. Breech presentation is such an issue due to its contribution to the rising caesarean section (CS) rate. We set out to assess the management of breech presentation using, as standards, the delivery suite protocol and national guidelines. Our first audit revealed a low success rate of external cephalic version (ECV) and deficient documentation of written consent for ECV, other aspects of care being satisfactory. The results were presented to a multidisciplinary meeting and disseminated to relevant stakeholders. A re-audit was then performed. It confirmed significant improvement in the documentation of consent for ECV. It also revealed a good detection rate of breech, optimal offer rate of ECV and good neonatal outcome. However, uptake of ECV as well as the success rate could both be improved so as to reduce the CS rate for breech presentation. We discuss options for improving the uptake and success rate for ECV.

Birth Injuries↗
PubMed2005

Neuroendocrine differentiation in non-small cell lung cancer and its relation to prognosis and therapy.

AIMS: Histopathologists report the presence of neuroendocrine (NE) differentiation in non-small cell lung carcinoma (NSCLC) in up to a third of cases and are often questioned about its clinical relevance. The conclusions of previous studies have been inconsistent. This paper aims to provide an answer by examining a large series together with a comprehensive critique of the literature. METHODS AND RESULTS: Four hundred and thirty-nine cases of NSCLC were examined, immunohistochemically, using antibodies to chromogranin A (CGA), synaptophysin (SYN) and CD56/neural cell adhesion molecule (NCAM). Three hundred and forty-one cases had been treated with surgical resection and the remainder with chemotherapy. The results were compared with clinical outcome. Thity-six percent of cases had positive staining for at least one NE marker. CGA was positive in 5.5% of cases, SYN in 16.5% and NCAM in 28%. There was no association between the presence of NE markers and survival in either the surgically treated group or the chemotherapy-treated group. There was also no association between NE markers and response to chemotherapy in the latter group. CONCLUSIONS: The presence of immunohistochemically detected NE differentiation in NSCLC is not of prognostic significance.

Adenocarcinoma↗
PubMed2004

Assessment of biological prognostic factors provides clinically relevant information in patients with diffuse large B-cell lymphoma--a Nordic Lymphoma Group study.

The purpose of this study was to investigate the prognostic effects of four biological markers, BCL2, TP53, Ki-67, and P-glycoprotein, and their possible clinical relevance in addition to the international prognostic index (IPI) in diffuse large B-cell lymphoma (DLBCL). A total of 405 patients with aggressive lymphoma, stage II-IV, between 18 and 67 years, were randomized in a trial comparing CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin). Of these, 267 cases were classified as DLBCL, with adequate paraffin blocks available in 207 cases, enabling immunohistochemical assessment of the expression of BCL2, TP53, P-glycoprotein, and Ki-67. In a multivariate analysis, stratified for IPI, high BCL2 expression (>10%) low (<60%) expression of Ki-67, and high TP53 protein expression (>75%) were shown to provide additional prognostic information with regard to overall or failure-free survival. We found no association between expression of P-glycoprotein and outcome. Assessment of BCL2 positivity might be introduced as part of the routine investigation in patients with DLBCL, but further studies are necessary to confirm the clinical relevance of Ki-67 and TP53 expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

HABITS (hormonal replacement therapy after breast cancer--is it safe?), a randomised comparison: trial stopped.

In the 1990s, two randomised clinical trials started in Scandinavia addressing whether hormone replacement therapy (HRT) is safe for women with previous breast cancer. We report the findings of the safety analysis in HABITS (hormonal replacement therapy after breast cancer--is it safe?), an open randomised clinical trial with allocation to either HRT or best treatment without hormones. The main endpoint was any new breast cancer event. All analyses were done according to intention-to-treat. Until September, 2003, 434 women were randomised; 345 had at least one follow-up report. After a median follow-up of 2.1 years, 26 women in the HRT group and seven in the non-HRT group had a new breast-cancer event. All women with an event in the HRT group and two of those in the non-HRT group were exposed to HRT and most women had their event when on treatment. We decided that these findings indicated an unacceptable risk for women exposed to HRT in the HABITS trial, and the trial was terminated on Dec 17, 2003.

Breast Neoplasms↗
PubMed2004

Familial risk of tumors associated with hereditary non-polyposis colorectal cancer: a Swedish population-based study.

BACKGROUND: Familial clustering, which may be due to inherited predisposition, is seen in several common cancer types. The aim of this study was to assess the familial risk of tumors that are associated with hereditary non-polyposis colorectal cancer (HNPCC), a familial cancer syndrome that confers an increased risk of several cancer types, and is associated with a low age at onset. METHODS: The National Swedish Cancer Registry and population registers were utilized to identify all tumors among the offspring of individuals who had developed any of the diagnoses included in the Amsterdam II criteria for HNPCC. In all, 204,358 offspring of 102,814 individuals with cancer of the colorectum, endometrium, upper urinary tract or small intestine were identified. RESULTS: Significantly increased risks for several tumor types were demonstrated. If the parent was below age 50 at diagnosis, the offspring Standard Incidence Ratios (SIRs) were 3.6 for colon cancer, 3.8 for rectal cancer, 2.8 for gastric cancer, and 2.3 for ovarian cancer. Offspring who had both a parent and a sibling with HNPCC-associated cancer showed even higher SIRs for cancer of the colorectum, endometrium, ovary, and urinary tract. The highest values were observed in the subgroup whose parent had developed multiple primary tumors; SIR 34.0 for colon cancer, 17.9 for rectal cancer, 21.8 for endometrial cancer, and 5.8 for ovarian cancer. CONCLUSIONS: The study demonstrates that there is an increased risk for several tumor types among individuals whose parents developed HNPCC-associated tumors, where a young age at diagnosis and development of multiple tumors in the parents lead to the highest SIRs.

Adult↗
PubMed2004

SRL172 (killed Mycobacterium vaccae) in addition to standard chemotherapy improves quality of life without affecting survival, in patients with advanced non-small-cell lung cancer: phase III results.

BACKGROUND: This open-label, randomised phase III study was designed to further investigate the clinical activity and safety of SRL172 (killed Mycobacterium vaccae suspension) with chemotherapy in the treatment of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomised to receive platinum-based chemotherapy, consisting of up to six cycles of MVP (mitomycin, vinblastine and cisplatin or carboplatin) with (210 patients) or without (209 patients) monthly SRL172. RESULTS: There was no statistical difference between the two groups in overall survival (primary efficacy end point) over the course of the study (median overall survival of 223 days versus 225 days; P = 0.65). However, a higher proportion of patients were alive at the end of the 15-week treatment phase in the chemotherapy plus SRL172 group (90%), than in the chemotherapy alone group (83%) (P = 0.061). At the end of the treatment phase, the response rate was 37% in the combined group and 33% in the chemotherapy alone group. Patients in the chemotherapy alone group had greater deterioration in their Global Health Status score (-14.3) than patients in the chemotherapy plus SRL172 group (-6.6) (P = 0.02). CONCLUSION: In this non-placebo controlled trial, SRL172 when added to standard cancer chemotherapy significantly improved patient quality of life without affecting overall survival times.

Adult↗
PubMed2004

Summer work and injury among middle school students, aged 10-14 years.

BACKGROUND: Little information exists on injury and factors associated with injury in working youth aged 10-14 years. Most studies do not involve children younger than 15. METHODS: A cross-sectional anonymous survey was administered to middle school students in five school districts and one large urban school in October 2001. RESULTS: Of the 3189 working middle school students who responded to the survey, the majority were employed in informal job settings, such as working for someone in a home, newspaper delivery, and working on family farms or in family businesses. Overall, 18% of children reported being injured at work. Of those injured, 26% reported that their injury was severe enough to affect their activities for more than three days. Variables that were associated with injury included having a "near-miss" incident at work (AOR 6.61, 95% CI 4.92 to 8.89), having a co-worker injured (AOR 2.65, 95% CI 1.95 to 3.60), and being asked to do something dangerous (AOR 2.25, 95% CI 1.61 to 3.14). CONCLUSIONS: Children are working and being injured in jobs that are not covered by existing child labour laws. Injury rates in non-covered occupations are high, warranting review of current laws.

Accidents, Occupational↗
PubMed2003

Domiciliary chemotherapy with gemcitabine is safe and acceptable to advanced non-small-cell lung cancer patients: results of a feasibility study.

A study was conducted to investigate the feasibility and acceptability of administering single-agent gemcitabine to patients with advanced non-small-cell lung cancer (NSCLC) in their own homes. Gemcitabine is an active agent in NSCLC with a good toxicity profile and lends itself to this type of investigation. A total of 24 patients were studied; as only one patient required gemcitabine to be changed from home administration to hospital administration, domiciliary gemcitabine is feasible. A total of 249 injections of gemcitabine were given, the mean number of courses being 3.5, range 1-6. The gemcitabine was given at 1000 mg m(-2) on days 1, 8 and 15, the courses being repeated every 28 days. All patients received their first course in hospital and in total 147 were given at home and only 14 in hospital on courses 2-6. Furthermore, both the patients and carers reported positively on the use of domiciliary gemcitabine and preferred it over hospital administration. There was no evidence of increasing burden to community services during the domiciliary chemotherapy. Further studies investigating this approach are warranted.

Aged↗
PubMed2003

Modified de Gramont with oxaliplatin in the first-line treatment of advanced colorectal cancer.

We previously reported high activity for oxaliplatin and a modified de Gramont regimen (OxMdG) in a single centre study of patients with metastatic colorectal cancer. We now report results with a further 56 patients treated at 14 centres. Low rates of grade 3 and 4 toxicity were seen, with no toxic deaths. Objective response rates were CR/PR=53%; NC=34.7%; PD=12.2%. Median time to progression was 8.3 months and overall survival was 14.5 months. This regimen is more convenient than those based around the conventional de Gramont regimen but is highly active and well tolerated; it forms part of a current UK MRC phase 3 trial.

Adult↗
PubMed2003

Measurement of renal tumour and normal tissue perfusion using positron emission tomography in a phase II clinical trial of razoxane.

Measurement of tumour and normal tissue perfusion in vivo in cancer patients will aid the clinical development of antiangiogenic and antivascular agents. We investigated the potential antiangiogenic effects of the drug razoxane by measuring the changes in parameters estimated from H(2)(15)O and C(15)O positron emission tomography (PET) to indicate alterations in vascular physiology. The study comprised 12 patients with primary or metastatic renal tumours >3 cm in diameter enrolled in a Phase II clinical trial of oral razoxane. Perfusion, fractional volume of distribution of water (VD) and blood volume (BV) were measured in tumour and normal tissue before and 4-8 weeks after treatment with 125 mg twice-daily razoxane. Renal tumour perfusion was variable but lower than normal tissue: mean 0.87 ml min(-1) ml(-1) (range 0.33-1.67) compared to renal parenchyma: mean 1.65 ml min(-1) ml(-1) (range 1.16-2.88). In eight patients, where parallel measurements were made during the same scan session, renal tumour perfusion was significantly lower than in normal kidney (P=0.0027). There was no statistically significant relationship between pretreatment perfusion and tumour size (r=0.32, n=13). In six patients scanned before and after razoxane administration, there was no statistically significant change in tumour perfusion: mean perfusion pretreatment was 0.81 ml min(-1) ml(-1) (range 0.46-1.26) and perfusion post-treatment was 0.72 ml min(-1) ml(-1) (range 0.51-1.15, P=0.15). Tumour VD and BV did not change significantly following treatment: mean pretreatment VD=0.66 (range 0.50-0.87), post-treatment VD=0.71 (range 0.63-0.82, P=0.22); pretreatment BV=0.18 ml ml(-1) (range 0.10-0.25), post-treatment BV=0.167 ml ml(-1) (range 0.091-0.24, P=0.55). Tumour perfusion, VD and BV did not change significantly with tumour progression. This study has shown that H(2)(15)O and C(15)O PET provide useful in vivo physiological measurements, that even highly angiogenic renal cancers have poor perfusion compared to surrounding normal tissue, and that PET can provide valuable information on the in vivo biology of angiogenesis in man and can assess the effects of antiangiogenic therapy.

Antineoplastic Agents↗
PubMed2003

Breast conservation surgery, with and without radiotherapy, in women with lymph node-negative breast cancer: a randomised clinical trial in a population with access to public mammography screening.

The effect of postoperative radiotherapy after sector resection for stage I-II lymph node-negative breast cancer was evaluated in a patient population with access to public mammographical screening. 1187 women were randomised to no further treatment or postoperative radiotherapy following a standardised sector resection and axillary dissection. Radiation was administered to a dose of 48-54 Gy. Median age was 60 years, and median size of the detected tumours was 12 mm. Of the women 65% had their tumours detected by mammographical screening. The relative risk (RR) of ipsilateral breast recurrence was significantly higher in the non-irradiated patients compared with the irradiated patients, RR=3.33 (95% Confidence Interval (CI) 2.13-5.19, P<0.001). The corresponding cumulative incidence at 5 years was 14% versus 4%, respectively. Overall survival (OS) was similar, RR=1.16 (95% CI 0.81-1.65, P=0.41), with 5 year probabilities of 93 and 94%, respectively. Recurrence-free survival (RFS) at 5 years was significantly lower in the non-irradiated women, 77% versus 88% (P<0.001). Although women above 49 years of age, whose tumours were detected with mammographical screening, had the lowest rate of ipsilateral breast recurrence in this study, the cumulative incidence of such event amounted to 10% at 5 years if radiotherapy was not given. Such a recurrence rate has been considered as unacceptably high, but is, however, in the same range as that reported after lumpectomy and postoperative radiotherapy in published series.

Adult↗