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Biomedical subjects

J R Yarnold

Publications and source records attributed to J R Yarnold.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1988

Carboplatin (JM8), etoposide (VP16) and thoracic irradiation for small cell lung cancer (S.C.L.C.): an evaluation of lung toxicity.

Carboplatin (JM8) and etoposide (VP16) have demonstrated activity against a range of solid tumours. A retrospective study has looked for evidence of enhanced radiation pneumonitis when these drugs are employed in conjunction with irradiation. Twenty-nine patients with limited disease small cell lung cancer (S.C.L.C.) received JM8 (300 mg/m2) and VP16 (300 mg/m2) at intervals of 3-4 weeks for 4 cycles followed by thoracic irradiation. Twenty-one were evaluated and compared with 21 matched non-S.C.L.C. patients treated by radiotherapy alone. Patients were stratified into three groups according to the radiation dose schedule normalised using Wara's modification of Ellis' formula (n = 0.38, t = 0.06) [28]. Group 1 received less than 1014 rets, Group 2 1015-1250 rets and Group 3 greater than 1250 rets. Radiological pneumonitis was observed in 57% (12/21) of patients receiving combined modality treatment compared to 71% (15/21) of patients receiving radiation alone with evidence of a radiation dose-response relationship for the appearance of pneumonitis in both groups of patients (p greater than 0.1). In conclusion, no enhancement of radiation pneumonitis by carboplatin (JM8) or etoposide (VP16) has been observed.

Adult↗
PubMed1988

Benefits expected from simple conformal radiotherapy in the treatment of pelvic tumours.

In 20 patients with invasive bladder cancer suitable for radical radiotherapy, a simple conformal planning technique has been compared with conventional beam arrangements in terms of normal tissue sparing. The median treatment volume for the group was reduced from 2275 to 1416 cm3 by the introduction of conformal planning. More specifically, in 13/20 patients (65%) the percentage volume of rectum irradiated to 90% of the isocentric dose was reduced by more than 30%, although the extent of rectal sparing varied greatly between patients. Overall, conformal planning appeared to be less successful at reducing the volume of large and small bowel irradiated to high dose. However, the data suggest that considerable benefit can be expected for those patients most at risk of morbidity by virtue of high bowel volumes included within the treatment length. A randomised trial is now being set up to determine the clinical impact of this planning technique in terms of reduced bowel morbidity.

Humans↗
PubMed1988

Patterns of breast relapse after local excision +/- radiotherapy for early stage breast cancer.

One hundred patients with breast recurrence have been identified from patients at the Royal Marsden Hospital, treated by local excision +/- radiotherapy for early stage primary invasive breast cancer between 1961 and 1985. The mean follow-up was 58 months (range 1 month - 19 years). In 74/100 patients, breast recurrence occurred within the breast parenchyma, was not associated with systemic relapse and carried a relatively good prognosis with a median survival of 77 months from the time of breast relapse. In 67 patients with parenchymal relapse in whom the site of relapse could be reliably compared with that of the original tumour, 60 (90%) patients developed recurrent tumours at or close to the primary site. In 24/100 patients, breast recurrence occurred in the overlying skin and in only two of these patients (2% of total) did recurrence actually occur within the scar tissue. Skin relapse was associated with systemic relapse and carried a relatively poor prognosis with a median survival of 36 months from the time of recurrence. The pattern of breast relapse was similar in irradiated and unirradiated patients. Skin relapse appears to be a manifestation of metastatic disease while parenchymal relapse may represent regrowth of primary tumour. This pattern of breast relapse questions the requirement for radiotherapy to the whole breast after local excision for early stage breast cancer.

Adult↗
PubMed1987

The severity of late skin damage related to fraction size in women treated by radiotherapy after mastectomy.

A retrospective study has been undertaken to test the NSD formula as a predictor of isoeffective schedules in women treated after mastectomy by parasternal radiotherapy using fraction sizes of 2-3 Gy. Forty three women were identified who have been treated on the same orthovoltage unit 8-18 years previously and the severity of overall skin changes and telangiectasia were assessed by three observers using a 4-point categorical scale. At each level of skin damage, radiotherapy schedules delivered using fraction sizes of 250 R or 300 R were associated with lower TDF values than schedules using 225 R fraction. The difference between TDF factors for isoeffective regimes using small (225 R) and large (250 R and 300 R) fraction sizes is highly significant for both overall skin damage and telangiectasia (p = 0.004 by rank sum test). Care should be exercised when using current empirical formulae to calculate regimes isoeffective for late skin damage, even when modest changes in fraction size from 2 to 3 Gy are contemplated.

Adult↗
PubMed1987

Clinical dosimetry for radiotherapy to the breast based on imaging with the prototype Royal Marsden Hospital CT simulator.

The result of conservative management of breast cancer is strongly dependent on the homogeneity of the dose delivered a schedule of post-surgical radiotherapy. In addition to improvements in local control, late normal-tissue effects should be minimised by achieving a good dose homogeneity. The Royal Marsden Hospital prototype CT simulator has been used to image patients in the treatment position. With the CT data incorporated into the planning process a quantitative measure of the dose homogeneity was made. There are strong indications that unless tissue compensators are used and/or conformation therapy is performed, the dose inhomogeneity in a widely used treatment geometry is too large to be clinically acceptable.

Breast Neoplasms↗
PubMed1987

Carboplatin (Paraplatin; JM8) and etoposide (VP-16) as first-line combination therapy for small-cell lung cancer.

Fifty-two previously untreated patients with small-cell lung carcinoma (SCLC) were treated with a combination of carboplatin 300 mg/m2 intravenously (IV) on day 1 and etoposide 100 mg/m2 IV on days 1 through 3 every 28 days for four courses. Patients with limited disease (LD) subsequently received thoracic radiotherapy; no prophylactic cranial radiotherapy was used. Forty-four patients (85%) achieved an objective response, including 82% (29% complete remissions) of LD patients and 88% (13% complete remissions) of extensive-disease (ED) patients. Median response duration for LD patients was 7 months and 5.5 months for ED patients. Median survival for both LD and ED patients was 9.5 months. Myelosuppression was the main toxicity, with World Health Organization (WHO) grade 3/4 leucopenia occurring in 44% of patients. There was one (2%) treatment-related neutropenic death. Treatment was otherwise well tolerated, and in particular no renal toxicity, neurotoxicity, or ototoxicity was seen. This new combination is highly active in terms of response rate, but response duration and survival is disappointing, and might be improved by prolonged treatment or by the use of additional drugs in combination.

Adult↗