Background Neoadjuvant chemotherapy (NACT) is increasingly used for managing locally advanced and high risk non‐metastatic breast cancer. Aims To describe trends in NACT use, assess compliance to best practice recommendations and determine treatment response rates in a regional cancer treatment service. Methods In this retrospective cross‐ sectional study, electronic records of patients who underwent NACT in centres covered by the MidCentral Regional Cancer Treatment Service in 2013 and 2017 were reviewed. Data pertaining to patient demographics, disease status, compliance to best practice recommendations and treatment outcomes were extracted and analysed. Results Of a total of 502 referrals for non‐metastatic breast cancer, 34 underwent NACT with the estimated NACT rate rising from 3.85% (2013) to 9.92% (2017). Compliance to practice recommendations improved in all domains (pre‐treatment tumour and axillary evaluation, marker placement, multidisciplinary discussion). Overall, NACT was well tolerated with only three patients experiencing treatment limiting toxicity. Response rates mirror published data (complete response: 29.4%, partial: 61.8%) with higher responses registered in HER2 positive and triple negative subtypes. Discordance between radiological and pathological response was 28%, with imaging overestimating response in five out of seven cases. Of the 11 (32%) patients who initially underwent breast conserving surgery, six required a second surgery. Conclusion NACT is increasingly used in the Regional Cancer Treatment Service, with improving compliance to practice recommendations. These results are reassuring and can be used to help patients develop a realistic expectation towards NACT.
The pathophysiology of thrombotic thrombocytopenic purpura (TTP) relates the ADAMTS 13 protease deficiency as a result of an inhibitor in acquired TTP, such as secondary to malignancy. Relapsing TTP is due to the inhibition or relative deficiency of von Willibrand factor (vWf)-cleaving protease activity preventing the breakdown of unusually large multimers of vWf, with resultant platelet adhesion to the subendothelium, platelet aggregation, and endothelial damage (Nabhan, 2003). We describe the manifestation of TTP as marker for rectal cancer disease recurrence and progression. A 60 y/o black male with Dukes C2 rectal cancer was treated with surgical resection, local radiation and six months of adjuvant fluoruracil and leucovorin. Two years later, he presented with fatigue, shortness of breath and confusion. He had a hemoglobin of 7.0 g/dl, platelets of 20,000, 2+ schistocytes, and acute renal failure with a creatinine of 1.5 mg/dl. TTP was confirmed with decreased ADAMTS 13 protease activity <6%(nl 67–177%) and the presence of an ADAMTS 13 inhibitor of 0.5u (nl 0–0.4u). Plasmaphoresis and high dose steroids were initiated with very good response. His evaluation revealed a carcinoembryonic antigen (CEA) of 11.4 μg/L (normal <3.0 μg/L) and CT scan showed a new solitary liver mass. After optimal response from plasmapheresis, the liver lesion was surgically resected and pathology confirmed metastatic rectal adenocarcinoma. His TTP improved and after resection his ADAMTS 13 inhibitor was <0.4 and ADAMTS activity had improved to 49%, but was not normal. This suggests that the resection was not curative. He was tapered off plasmaphoresis for several months. TTP relapse occurred, with ADAMTS inhibitor present at 0.9 IU and activity of <6%, prior to confirmation of numerous new hepatic lesions on CT scan. Palliative chemotherapy with FOLFIRI (irenotecan, 5-FU, and leucovorin) achieved a partial remission of his rectal cancer. He also had a good therapeutic response for his relapsed TTP, with improved ADAMTS 13 activity to 27%, but continued to required weekly maintenance plasmapheresis prior to chemotherapy. Progression of his rectal cancer was preceded by relapsed TTP, requiring intensification of treatment with increased frequency of plasmapheresis. CT scan and rising CEA confirmed rectal cancer progression, and his chemotherapy was changed to XELOX (capecitabine and oxaliplatin). Response to chemotherapy correlated with stable disease with regards to his TTP. Thrombotic thrombocytopenic purpura and the related hemolytic uremic syndrome (HUS) are rare, but well described complications in patients with adenocarcinomas, including gastrointestinal, pancreatic, breast and prostate primaries. TTP has also been described following treatment with certain chemotherapeutic agents, including cisplatin, gemcitabine, bleomycin and mitomycin C. Only one case has been reported in the literature of TTP relapse at the time of tumor progression, and this was a patient with breast cancer (Amer. J. Clin. Oncology23(1): 74-7, 2000). However, there is no report of recurrent TTP-HUS serving as a marker for solid tumor disease recurrence with correlative ADAMTS 13 protease activity and inhibitor. We conclude that effective treatment of the primary adenocarcinoma is crucial to the control of malignancy associated thrombotic thrombocytopenic purpura, and ADAMTS 13 inhibiter and activity levels are important clinical indicators of disease progression and response to treatment.
The MDS are heterogeneous clonal stem cell disorders. Dysplastic changes in morphology and functional abnormalities in multiple cell lines precede leukemic transformation in most patients. An abnormal immunophenotype has been identified in some hematopoetic clonal disorders on flow cytometric analysis. However, no clear immunophenotypic aberrancies, such as loss of differentiation or cross expression of markers of different lineages, have been described in MDS. We performed this retrospective analysis to identify an immunophenotypic signature distinguishing MDS from secondary causes of cytopenia on flow cytometric analysis. Data were reviewed for patients who had bone marrow aspirate and biopsy performed at our institution from 2000 to 2004 for evaluation of cytopenias or dysplasia in peripheral blood. Patients who had a non-MDS hematological malignancy, other neoplasms involving the bone marrow, or cytopenias secondary to chemotherapy were excluded. Flow cytometry was done on unfractionated bone marrow aspirates using a standardized panel including CD5, CD10, CD34, CD11c, CD117, CD19, CD20, CD22, CD14, CD56, CD33, CD13, CD2, CD8, CD4, CD3, CD7, CD24, CD16, kappa, and lambda antibodies. Ten of 93 cases were found to have a non-MDS malignant disorder or chemotherapy induced cytopenia and were excluded from analysis. Of the remaining 83 cases, MDS was diagnosed based on morphology and cytogenetic findings in 29 cases. Twenty-one patients had refractory anemia (RA), one had RA with ringed sideroblasts, six had RA with excess of blasts and one had treatment related MDS. The remaining patients had cytopenias secondary to infection, peripheral consumption, inflammation, autoimmune disease or medications. The median age was 74 for the MDS group and 54 for non-MDS group. Data for International Prognostic Scoring System (IPSS) was available for 17 patients. Three had a low IPSS, 5 were Intermediate-1, 6 were Intermediate-2, and 3 were high. Flow cytometric immunophenotyping was useful in characterizing and enumerating myeloblasts in the blast gate (CD45 dim positive/negative, low complexity side scatter) in all patients with RAEB (n=6). Interestingly, aberrant CD34 expression was seen in a fraction of cells in the neutrophil gate (CD45 bright positive, high complexity side scatter) in six patients (20.6%) with refractory anemia with no blasts morphologically. This feature was not present in the non-MDS group (P<0.01). However, loss of CD10 expression on myelomonocytic cells was seen in four MDS patients (14.8%) and in 2 non-MDS patients (3.2%) (P=0.1). No other aberrant phenotypic pattern clearly distinguished between the MDS and non-MDS groups. An increased number (>10% in the lymphocyte gate) of CD56 and CD2 positive NK cells was seen in both groups (44.8% of MDS group and 40.7% of non-MDS). In conclusion, flow cytometric analysis may be useful in characterization and enumeration of blasts in RAEB. Although no consistent, characteristic immunophenotypic abnormalities were identified, expression of CD34 and loss of CD10 on dysplastic granulocytes in the bone marrow of a subset of patients with MDS may represent asynchronous expression of immunophenotypic markers suggestive of arrest in differentiation and warrants further exploration.
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