Two hundred and seventy-seven consecutive patients with T3b-T4 breast cancer referred to the Milan Cancer Institute between 1973 and 1980 were treated with a combined modality approach. Chemotherapy (CT) consisted of AV, i.e. adriamycin (60-75 mg/m2 day 1) and vincristine (1.2 mg/m2 days 1 and 8) and was given for three to four cycles prior to local regional modality. Local-regional treatment consisted of either radiotherapy (RT) in 198 patients or surgery (S) in 79 women. Additional chemotherapy was then administered to a total of 205 patients. In the absence of distant metastases, frequency of good local control was significantly inferior in patients given CT + RT (63.9 per cent) compared to those treated with CT + RT + CT (75.4 per cent) and CT + S + CT (82.3 per cent, P = 0.033). Also freedom from progression (FFP) and overall survival (SURV) were significantly superior in the groups receiving more prolonged chemotherapy treatment compared to patients treated with CT + RT (FFP: P less than 0.0001; SURV: P = 0.002). None of the variables examined was able to affect the response rate, while axillary nodal status and tumor size played a major role in the duration of FFP and SURV. Our findings indicate that a more aggressive treatment is needed to improve current results in this stage of disease. To overcome the problem of local-regional recurrence, treatment should probably begin with cytoreductive surgery followed by postoperative radiotherapy in all patients with the exception of those having inflammatory carcinoma. Systemic treatment should then be delivered to control distant micrometastases.
Background
Most terminally ill cancer patients prefer to die at home, but a majority die in institutional settings. Research questions about this discrepancy have not been fully answered. This study applies artificial intelligence and machine learning techniques to explore the complex network of factors and the cause-effect relationships affecting the place of death, with the ultimate aim of developing policies favouring home-based end-of-life care.
Methods
A data mining algorithm and a causal probabilistic model for data analysis were developed with information derived from expert knowledge that was merged with data from 116 deceased cancer patients in southern Switzerland. This data set was obtained via a retrospective clinical chart review.
Results
Dependencies of disease and treatment-related decisions demonstrate an influence on the place of death of 13%. Anticancer treatment in advanced disease prevents or delays communication about the end of life between oncologists, patients and families. Unknown preferences for the place of death represent a great barrier to a home death. A further barrier is the limited availability of family caregivers for terminal home care. The family’s preference for the last place of care has a high impact on the place of death of 51%, while the influence of the patient’s preference is low, at 14%. Approximately one-third of family systems can be empowered by health care professionals to provide home care through open end-of-life communication and good symptom management. Such intervention has an influence on the place of death of 17%. If families express a convincing preference for home care, the involvement of a specialist palliative home care service can increase the probability of home deaths by 24%.
Conclusion
Concerning death at home, open communication about death and dying is essential. Furthermore, for the patient preference for home care to be respected, the family’s decision for the last place of care seems to be key. The early initiation of family-centred palliative care and the provision of specialist palliative home care for patients who wish to die at home are suggested.
Pharmacokinetic measurements to monitor and design cytotoxic treatments in cancer patients are being used more and more in order to optimize dosage and administration schedules. Ideally, information on drug concentrations over time should help reveal dose—response correlations. The cytotoxic drugs carmustine, etoposide, cyclophosphamide, iphosphamide, cis‐diammineplatinum, Adriamycin (doxorubicin), and 4′‐epi‐Adriamycin have been monitored on different treatment programs of patients with advanced lung cancers. The collected experience emphasizes the many individual variables encountered in clinical practice complicating the effort of correlating pharmacokinetic data with clinical results. The examples, presented on the basis of the authors' experiences, pertain to drug instability, gastrointestinal absorption, enzymatic induction in the liver, drug interaction, and drug tissue concentrations.
The implications of these results are that initial endocrine therapy in postmenopausal patients with metastatic disease should be MAP if the patient is willing to accept the side effects of high-dose progestins. Progestins should be tested in the adjuvant setting for postmenopausal women, especially those with no tendency to hypertension or obesity.
The feasibility and reliability of an in vitro assay that evaluates drug interference on nucleic acid precursor incorporation were investigated on 135 previously untreated locally advanced breast cancers. The assay, which was carried out on tumor fragments incubated for 3 hours with drugs, proved to be feasible on a sufficiently high percentage of biopsy specimens (70%) for routine clinical use. In vitro drug activity evaluated with this assay appeared to reproduce the clinical patterns of sensitivity of the tumor type as well as of the individual tumors. In fact, in vitro response rates to conventional agents resembled the clinical response rates reported for the same agents used in monochemotherapy. From a retrospective--correlative study carried out on 41 patients treated in vitro and in vivo with the same drugs (Adriamycin [doxorubicin] and vincristine), in vitro effect of Adriamycin on 3H-uridine incorporation appeared significantly correlated with clinical response (overall agreement, 78%; P = 0.0032) with specific agreements of sensitivity and resistance of 75% and 81%, respectively.
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