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Biomedical subjects

J R Yarnold

Publications and source records attributed to J R Yarnold.

At least 19 recordsLinked to original sources
PubMed1992

Prediction of normal-tissue tolerance to radiotherapy from in-vitro cellular radiation sensitivity.

The success of radiotherapy depends on the total radiation dose, which is limited by the tolerance of surrounding normal tissues. Since there is substantial variation among patients in normal-tissue radiosensitivity, we have tested the hypothesis that in-vitro cellular radiosensitivity is correlated with in-vitro normal-tissue responses. We exposed skin fibroblast cell lines from six radiation-treated patients to various doses of radiation and measured the proportions surviving. There was a strong relation between fibroblast sensitivity in vitro and normal-tissue reactions, especially acute effects. Assessment of radiosensitivity could lead to improved tumour cure rates by enabling radiation doses to be tailored to the individual.

Breast Neoplasms↗
PubMed1992

Weight gain after primary surgery for breast cancer--effect of tamoxifen.

Changes in body weight have been studied in 92 consecutive patients with primary breast cancer from the time of initial diagnosis and treatment. Sixty patients receiving tamoxifen were compared with 32 controls receiving no hormone treatment. Weight gain was seen in both groups, but was greater in the group receiving tamoxifen. Premenopausal women receiving tamoxifen had greater weight gain than postmenopausal women on tamoxifen therapy.

Adult↗
PubMed1992

Selective avoidance of lymphatic radiotherapy in the conservative management of early breast cancer.

In view of the morbidity and potential mortality associated with routine post-operative lymph node radiotherapy in women with early stage breast cancer, an attempt has been made to select patients in whom radiotherapy can be withheld. Three hundred and forty-seven consecutive patients treated wide local excision plus or minus axillary surgery have been evaluated. Only 20% were subsequently given radiotherapy to regional nodes. Relapse in the axilla, the supraclavicular fossa or at both these sites have occurred in 16 patients so far, 12 of whom were successfully treated. Systemic relapse was seen in eight of these patients occurring with one exception before or within 3 months of node relapse. Only four have persisting symptoms as a result of nodal relapse. So far, a policy involving selective lymphatic radiotherapy in women treated for early breast cancer appears justified.

Axilla↗
PubMed1992

Cosmetic and functional outcomes of breast conserving treatment for early stage breast cancer. 1. Comparison of patients' ratings, observers' ratings, and objective assessments.

The cosmetic and functional results of breast conserving therapy were evaluated in a sample of 76 patients with early stage breast cancer, treated by wide local excision, axillary dissection and postoperative radiotherapy between 1975 and 1985. A comparison was made between patients' ratings, independent ratings by two observers (an oncology nurse and a radiation oncologist) and objective measurements. In approximately 40% of the cases, moderate to large differences in the appearance of the treated versus the untreated breast were reported by patients and clinical observers alike. When evaluated on an individual level, the observers' ratings showed relatively high inter-rater agreement (kappa = 0.64), but low levels of concordance were found between the patients' and observers' ratings (kappa < 0.10). Approximately half of the patients reported limited arm or shoulder function, generally mild in nature. Compared to the patients', the observers' ratings of arm edema were significantly lower, indicating 20% mild and 5% more severe swelling. Objective measures of cosmesis and function correlated moderately with the observers' and patients' ratings. Both cosmetic and functional results were found to be significantly related to time elapsed since treatment, with patients treated longer ago exhibiting more problems. The cosmetic and functional outcomes were not related to the patients' age. The results suggest that the patients' opinion can provide important additional information in the evaluation of cosmetic and functional results of breast conserving treatment.

Adult↗
PubMed1992

Cosmetic and functional outcomes of breast conserving treatment for early stage breast cancer. 2. Relationship with psychosocial functioning.

The relationship between cosmetic and functional results of breast conserving therapy and psychosocial functioning was examined in a sample of 76 patients with early stage breast cancer, who received treatment between 1975 and 1985. The patients were interviewed at their homes regarding breast cosmesis, arm functioning and psychosocial health, and subsequently attended the hospital for independent assessment of cosmetic and functional outcomes by clinical observers. High levels of psychological distress, disturbance of body image, and decreased sexual functioning were noted in approximately one-quarter of the study sample. About half of the patients expressed heightened concern with disease recurrence and their future health. Psychosocial problems were only modestly associated with treatment-related cosmetic and functional outcomes, as determined by clinical ratings and objective assessments. The patients' own ratings of breast cosmesis and arm functioning exhibited somewhat higher correlations with self-reported psychosocial functioning. In particular, a significant association was noted between the patients' ratings of overall cosmesis and arm edema and their body image (r = 0.48 and r = 0.43, respectively). The association between cosmetic and functional results and self-reported psychosocial health was strongest among those patients younger in age and treated longer ago. These findings suggest that, in order to evaluate the impact of breast conserving therapy on the patients' quality of life, the patients' own assessments of cosmetic and functional outcomes should be used as a primary source of information.

Adult↗
PubMed1992

A prospective randomised trial of 4 Gy or 8 Gy single doses in the treatment of metastatic bone pain.

270 patients with painful bone metastases requiring palliative radiotherapy were randomised to receive single fractions of 4 Gy or 8 Gy in a randomised trial. Pain scores and analgesic usage were recorded before treatment and at 2, 4, 8 and 12 weeks. Pain was assessed by patients on a 4 point graded scale using pain charts administered by a central trials office. Response was defined as an improved rating compared to the pretreatment value. Compliance with the pain chart was 72% at 4 weeks. At 4 weeks, the actual response rates were 69% for 8 Gy and 44% for 4 Gy (p less than 0.001), but there was no difference in complete response (no pain) rates at 4 weeks or duration of response between the two arms. It is concluded that 8 Gy gives a higher probability of pain relief than 4 Gy, but that 4 Gy can be an effective alternative in situations of reduced tolerance.

Bone Neoplasms↗
PubMed1992

What are cancer genes, and how do they upset cell behaviour?

Some of the cellular changes underlying the presentation of cancer in a patient can already be understood in terms of mutations affecting specific gene functions. So far, only a few of the mutated genes responsible for carcinogenesis have been identified and these are chiefly involved in deregulation of cell growth rather than with the processes of invasion and metastasis. Proto-oncogenes are important cellular genes which can acquire gain in function mutations as random events in somatic cells. In their mutated, activated forms they are called cellular oncogenes or c-oncs. This distinguishes them from homologous DNA sequences captured by viruses from host cells in the course of retroviral evolution that cause cancers in animal hosts (viral oncogenes or v-oncs). In recent years, loss of function mutations have been identified in regulatory genes that normally serve to constrain cell growth. These are called tumour suppressor genes. Loss of function mutations may be transmitted in the germline, as in hereditary retinoblastoma, or arise de novo in somatic cells. The normal molecular mechanisms disrupted by mutations in tumour suppressor genes include processes regulating progression through the cell cycle.

Adult↗
PubMed1991

Intercalated radio-chemotherapy in small cell lung cancer: toxicity and implications for future regimens.

Thirty-six patients with small cell lung cancer have been treated using chemotherapy comprising carboplatin, ifosphamide and etoposide. A total of six cycles of chemotherapy were given. In 15 patients with limited disease intercalated radio-chemotherapy was used in which two 5-day courses of hyperfractionated radiotherapy were given to the thorax after the first and second cycles of chemotherapy. Each course of thoracic radiotherapy delivered 15 Gy in 15 fractions over 5 days. Oesophagitis occurred in 7 patients (40%), in 5 of whom this was severe (WHO grade 3). Radiological pneumonitis developed in 6 patients (40%) with subsequent fibrosis in 2 patients. These effects are greater than would be expected with this dose of radiation alone and reflect marked enhancement of normal tissue toxicity.

Adult↗
PubMed1991

Improved dose homogeneity in the breast using tissue compensators.

The improvements achievable by introducing individual tissue compensators in photon therapy of the breast were assessed. In 37 patients the dose ranged from +15% to -10% of the mid target dose using combinations of wedge filters and beam weights alone. With a tissue compensator the dose ranged from +4% to -11% provided that allowance was made for lung attenuation. A megavoltage imaging system is a potential source of the X-ray transmission data which can provide a basis for the calculation of thickness of the compensator.

Breast Neoplasms↗
PubMed1991

Early stage breast cancer: treatment options and results.

Large randomized clinical trials have redefined patterns of spread which have major implications for treatment options and outcomes in early stage breast cancer. Trials comparing mastectomy plus radiotherapy with mastectomy alone in women with T1-2 N0-1 M0 disease show clearly that the probability of developing distant metastases is unaffected by treatment of the lymphatic pathways. The inference is that, for the vast majority of women presenting with early stage disease, the cancer is either confined to the breast or else disseminated via vascular and lymphatic channels more or less simultaneously. Breast cancer is almost unique in that distant metastases may remain occult for several decades before becoming clinically apparent by mechanisms which remain unclear. The probability of haematogenous dissemination correlates closely with tumour size and this observation is the basis of population-based screening programmes discussed elsewhere in this issue. By identifying tumours earlier in their evolution, effective treatment of the primary disease is expected to be curative in a greater proportion of women. The implications for breast conserving management of women with early stage breast cancer are that initial surgery and radiotherapy must be of a high quality and promptly delivered if the expected reductions in breast cancer mortality are to materialize.

Adult↗
PubMed1990

Carboplatin, etoposide, and ifosfamide as intensive chemotherapy for small-cell lung cancer.

Thirty-two previously untreated, fit patients with small-cell lung carcinoma (SCLC) were treated with an intensive combination chemotherapy regimen, with the aim of prolonging survival, as follows: carboplatin 400 mg/m2 intravenously (IV) day 1, ifosfamide 5 g/m2 IV day 1 in a 24-hour infusion with mesna, and etoposide 100 mg/m2 IV days 1 to 3, repeating at 28-day intervals for six courses. Limited-disease (LD) patients were given concurrent hyperfractionated radiotherapy for the first two courses, and all patients achieving a complete remission (CR) were offered prophylactic cranial irradiation (PCI). For 18 LD patients, the overall response was 94% with 72% CRs. For 14 extensive-disease (ED) patients the overall response was 100% with 29% CRs. Median response duration for LD patients was 11.5 months and for ED patients 7.5 months. Median survival for LD patients was 19 months with a predicted 24% 2-year survival and for ED patients 9.5 months with a predicted 14% 2-year survival. Hematologic toxicity was severe with 100% developing World Health Organization (WHO) grade 3-4 neutropenia and 94% WHO grade 3-4 thrombocytopenia during treatment. Seventy-two percent of patients required a dose reduction at some stage during treatment because of neutropenic infection or thrombocytopenia requiring platelet transfusions. Despite very high response rates, this intensive regimen achieves survival results only modestly better, if at all, than those reported for less toxic conventional regimens.

Adult↗
PubMed1988

Low dose single fraction radiotherapy in the treatment of metastatic bone pain: a pilot study.

Single fraction radiotherapy can be used effectively to palliate painful bone metastases. The optimal single dose of radiotherapy required for pain relief is unknown. Twenty-six patients have been treated with a single fraction of 4 Gy to the site of the bone pain. Partial pain relief was seen in 9/21 (5%). Response occurred within 3 weeks of radiotherapy. These results question the mechanism of pain relief following radiotherapy and suggest a method of pain control using single repeatable low dose treatments.

Aged↗