Purpose: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows noninvasive, in vivo measurements of tissue microvessel perfusion and permeability. We examined whether DCE-MRI done after two cycles of neoadjuvant chemotherapy could predict final clinical and pathologic response in primary breast cancers. Experimental Design: Thirty-seven patients with primary breast cancer, due to receive six cycles of neoadjuvant 5-fluorouracil, epirubicin and cyclophosphamide chemotherapy, were examined using DCE-MRI before neoadjuvant chemotherapy and after two cycles of treatment. Changes in DCE-MRI kinetic parameters (K trans , k ep , v e , MaxGd, rBV, rBF, MTT) were correlated with the final clinical and pathologic response to neoadjuvant chemotherapy.Test-retest variability was used to determine individual patient response. Results: Twenty-eight patients were evaluable for response (19 clinical responders and 9 nonresponders; 11 pathologic responders and 17 nonresponders). Changes in the DCE-MRI kinetic parameters K trans , k ep , MaxGd, rBV, and rBF were significantly correlated with both final clinical and pathologic response (P < 0.01). Change in K trans was the best predictor of pathologic nonresponse (area under the receiver operating characteristic curve, 0.93; sensitivity, 94%; specificity, 82%), correctly identifying 94% of nonresponders and 73% of responders. Change in MRIderived tumor size did not predict for pathologic response. Conclusion: Changes in breast tumor microvessel functionality as depicted by DCE-MRI early on after starting anthracycline-based neoadjuvant chemotherapy can predict final clinical and pathologic response. The ability to identify nonresponders early may allow the selection of patients who may benefit from a therapy change.
Primary systemic therapy (PST) for operable breast cancer enables the identification of in vivo biological markers that predict response to treatment. A total of 118 patients with T2 -4 N0 -1 M0 primary breast cancer received six cycles of anthracycline-based PST. Clinical and radiological response was assessed before and after treatment using UICC criteria. A grading system to score pathological response was devised. Diagnostic biopsies and postchemotherapy surgical specimens were stained for oestrogen (ER) and progesterone (PgR) receptor, HER-2 and cell proliferation (Ki-67). Clinical, radiological and pathological response rates were 78, 72 and 38%, respectively. There was a strong correlation between ER and PgR staining (Po0.0001). Higher Ki-67 proliferation indices were associated with PgRÀ tumours (median 28.3%, PgR þ 22.9%; P ¼ 0.042). There was no relationship between HER-2 and other biological markers. No single pretreatment or postchemotherapy biological parameter predicted response by any modality of assessment. In all, 10 tumours changed hormone receptor classification after chemotherapy (three ER, seven PgR); HER-2 staining changed in nine cases. Median Ki-67 index was 24.9% before and 18.1% after treatment (P ¼ 0.02); the median reduction in Ki-67 index after treatment was 21.2%. Tumours displaying 475% reduction in Ki-67 after chemotherapy were more likely to achieve a pathological response (77.8 vs 26.7%, P ¼ 0.004).
SUMMARY Perineural spread has been demonstrated histologically in 65/180 (36%) major surgical resections for squamous carcinomas of the head and neck; the incidence in a smaller necropsy series was 18/20 (90%). Perineural infiltration was observed most commonly in the vicinity of carcinomas arising in the buccal cavity (31/63, 50%) and, at all sites, it was most commonly encountered near tumours ¢2-5 cm in diameter. Perineural spread near cervical node metastases was, by contrast, uncommon cinomas of the major and minor salivary glands, but it is also a common feature of squamous carcinomas:5-9 The purpose of the present paper is twofold: (i) to record the incidence of perineural infiltration in a large series of squamous cancers of the head and neck, drawn from both surgical and necropsy material; (ii) to describe the detailed histopathology of the infiltrated nerves using two monoclonal antibodies directed against axonal and myelin components of human nervous tissue.
Tru-Cut biopsies were obtained from 52 consecutive patients referred with soft tissue tumours. Forty-five patients had soft tissue sarcomas; seven had benign soft tissue tumours. Of the biopsies 96 per cent provided adequate material for diagnosis. The histological diagnosis made from the Tru-Cut biopsy was compared with that made from the resected specimen. There were no false positive diagnoses of malignancy. The accuracy of Tru-Cut biopsy was 98 per cent for the diagnosis of malignancy and 94 per cent for the diagnosis of sarcoma. Tumour subtype was correctly specified in 85 per cent of sarcomas and tumour grade in 88 per cent. Tru-Cut biopsy should replace open biopsy as the primary means of diagnosis of soft tissue tumours unless a satisfactory tissue sample cannot be obtained.
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