Aims. In this retrospective comparison, we describe the differences in dose intensity, delays and toxicity between weekly Cisplatin and 3-weekly Cisplatin given concurrently to patients with locally advanced squamous head and neck cancer (SCCHN) at New Cross Hospital, Wolverhampton. Materials and methods. Fifty-one patients received radical Cisplatin based chemoradiotherapy for stage 4a SCCHN of the head and neck between September 2000 and December 2004. Twenty-seven patients were treated with 3-weekly inpatient Cisplatin for 3 cycles (20 patients-80 mg/m2; 7 patients-100 mg/m2) concomitantly with radiotherapy (66–70 Gy/33–35 fractions). Twenty-four patients received a similar radiotherapy schedule but received weekly Cisplatin 33–40 mg/m2. Results. More patients received a higher cumulative dose of at least 240 mg/m2 if given weekly Cisplatin 40 mg/m2 or 3-weekly Cisplatin 80 mg/m2 compared with those receiving Cisplatin 3-weekly 100 mg/m2 (p=0.04). Maximum cumulative dose achievable in the latter group was only 200 mg/m2 and none achieved the full 3 cycles. Mean Cisplatin dose in the weekly Cisplatin 40 mg/m2 regime (mean 202 mg/m2) and 3-weekly arm of 80 mg/m2 (mean 203 mg/m2) was higher than that reached if given 3-weekly Cisplatin 100 mg/m2 (mean 180 mg/m2) although statistically insignificant (p=0.39) due to the small number of patients. More delays (29% vs. 41%) and omission of chemotherapy (5.6% vs. 17.4%) occurred in the 3-weekly compared with the weekly regime. Toxicity, radiotherapy overall treatment time and delays were similar between the two groups. Conclusion. Delivery of 100 mg/m2 Cisplatin 3-weekly with radiotherapy was less tolerated than 40 mg/m2 weekly and resulted in less patients achieving cumulative dose beyond 200 mg/m2, potentially lowering chemotherapy dose intensity.
Abstract Purpose: To define a simple radiologic biomarker of prognosis in patients with advanced epithelial ovarian carcinoma on first-line chemotherapy. Experimental Design: Twenty-seven patients receiving platinum-based chemotherapy with >2 cm residual disease [International Federation of Gynecology and Obstetrics (FIGO) stages IIIC or IV] after surgery were identified. The proportion of enhancing tumor tissue—the enhancing fraction—was calculated on pre-chemotherapy computed tomography scans at four Hounsfield unit (HU) thresholds and assessed for correlation with CA125 response, Response Evaluation Criteria in Solid Tumors (RECIST) radiologic response, and time to progression. Discriminative power was assessed by leave-one-out discriminant analysis. Results: Pre-chemotherapy residual tumor volume did not correlate with clinical outcome. Pre-chemotherapy enhancing fraction at all thresholds significantly correlated with CA125 response (P < 0.001, ρ = 0.553 for 50 HU; P < 0.001, ρ = 0.565 for 60 HU; P < 0.001, ρ = 0.553 for 70 HU; P = 0.001, ρ = 0.516 for 80 HU). Significant correlations were also shown for radiologic response at all thresholds. Enhancing fraction predicted CA125 response with 81.9% to 86.4% specificity and Response Evaluation Criteria in Solid Tumors response with 74.9% to 76.8% specificity at 95% sensitivity (dependent on threshold). Enhancing fraction correlated with time to progression at the 60 HU (P = 0.045, ρ = 0.336) and 70 HU (P = 0.042; ρ = 0.340) thresholds. Conclusion: Pre-chemotherapy enhancing fraction is a simple quantitative radiologic measure. Further evaluation in larger trials is required to confirm the potential of enhancing fraction as a predictive factor, particularly for patients who may benefit from the addition of antiangiogenic therapy.
Abstract Human mammary tumours which are histologically well differentiated are more likely to synthesize receptors for estrogen (ER) and progesterone (PR) and to respond to systemic endocrine therapy. The aim of this study was to explore the relationship between differentiation, receptors and endocrine responsiveness in more detail by relating the expression of putative differentiation antigens within tumours to ER, PR and response to treatment. Sections of the primary tumours of 160 patients with advanced evaluable breast cancer were immunostained with 2 monoclonal antibodies (MAbs) (HMFGI and HMFG2) raised against putative differentiation antigens found on the membranes which surround the milk fat globule. Tumours were highly heterogeneous with respect to antigen expression. However, the number of cells which expressed the antigens was highly correlated with ER and PR concentrations and with response to endocrine therapy. In tumours where ⩾ 20% of cells expressed the antigen recognized by HMFGI, 73% responded to endocrine therapy; this was similar to the response predicted by ER (67%) and PR (73%). Expression of HMFGI was correlated with survival from the start of endocrine therapy ( p < 0.0001) to the same degree as ER and PR. Patients with tumours which expressed ER, PR and HMFGI had the highest response rate (87%) and survival (median 49 months); the response in tumours which expressed none of these phenotypes was 13% and the median survival of these patients was 9 months. These results suggest that cells which express differentiation antigens also express ER and PR. Differentiated cells within mammary tumours may therefore be the target cells for systemic hormone, and also the source of factors which control tumour growth.
Summary. Indications for platelet transfusion remain controversial and are frequently based on arbitrary numerical criteria. In October 2000, we introduced a stringent prophylactic‐platelet transfusion policy < 10 × 10 9 /l for stable patients and < 20 × 10 9 /l in the presence of major bleeding or additional risk factors. A trigger of < 50 × 10 9 /l was introduced for patients undergoing invasive procedures. A prospective analysis was performed measuring the frequency of minor and major bleeding events, morbidity, mortality and duration of pancytopenia. Blood product usage was assessed and health care savings measured. A total of 98 patients were evaluated on 2147 patient study days and 271 bleeding episodes were recorded. Major bleeding occurred on 1·39% (30/2147) of the study days when platelet counts were < 10 × 10 9 /l and 2·3% (50/2147) of the study days when platelet counts were 10–20 × 10 9 /l. In patients with platelets > 20 × 10 9 /l, there were 117 major bleeding episodes observed on 5·4% of the study days. In patients with no identified additional risk factors present, major haemorrhages were recorded in 0·51% (11/2147) of the study days in patients with platelet counts ≥ 10 × 10 9 /l. There was a 36% reduction in platelet units transfused compared with retrospective data when an arbitrary transfusion trigger of 20 × 10 9 /l was in place ( P = < 0·02). Of note, a 16% reduction in red cell transfusions was recorded. These data confirm that the introduction of a transfusion trigger of < 10 × 10 9 /l in the absence of fresh bleeding and sepsis (> 38°C) is safe and has a significant impact on overall hospital transfusion costs.
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