BackgroundMagnetic resonance imaging (MRI) may guide breast cancer surgery by measuring residual tumor size post-neoadjuvant chemotherapy (NAC). Accurate measurement may avoid overly radical surgery or reduce the need for repeat surgery. This individual patient data (IPD) meta-analysis examines MRI’s agreement with pathology in measuring the longest tumor diameter and compares MRI with alternative tests.MethodsA systematic review of MEDLINE, EMBASE, PREMEDLINE, Database of Abstracts of Reviews of Effects, Heath Technology Assessment, and Cochrane databases identified eligible studies. Primary study authors supplied IPD in a template format constructed a priori. Mean differences (MDs) between tests and pathology (i.e. systematic bias) were calculated and pooled by the inverse variance method; limits of agreement (LOA) were estimated. Test measurements of 0.0 cm in the presence of pathologic residual tumor, and measurements >0.0 cm despite pathologic complete response (pCR) were described for MRI and alternative tests.ResultsEight studies contributed IPD (N = 300). The pooled MD for MRI was 0.0 cm (LOA: +/−3.8 cm). Ultrasound underestimated pathologic size (MD: −0.3 cm) relative to MRI (MD: 0.1 cm), with comparable LOA. MDs were similar for MRI (0.1 cm) and mammography (0.0 cm), with wider LOA for mammography. Clinical examination underestimated size (MD: −0.8 cm) relative to MRI (MD: 0.0 cm), with wider LOA. Tumors “missed” by MRI typically measured 2.0 cm or less at pathology; tumors >2.0 cm were more commonly “missed” by clinical examination (9.3 %). MRI measurements >5.0 cm occurred in 5.3 % of patients with pCR, but were more frequent for mammography (46.2 %).ConclusionsThere was no systematic bias in MRI tumor measurement, but LOA are large enough to be clinically important. MRI’s performance was generally superior to ultrasound, mammography, and clinical examination, and it may be considered the most appropriate test in this setting. Test combinations should be explored in future studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1664-4) contains supplementary material, which is available to authorized users.

Contrast-enhanced magnetic resonance imaging (MRI) was used to monitor the response of patients undergoing neoadjuvant chemotherapy for breast cancer with the aim of undergoing breast-conserving surgery (BCS). Patients were prospectively recruited to undergo MRI as well as conventional methods of clinical examination, mammography (MM) and ultrasonography (USS) and response was assessed by each of these methods. Thirty-two patients with primary breast cancer were recruited. Magnetic resonance imaging correlation with histopathological size (r ¼ 0.71) was superior to USS (r ¼ 0.65) and to MM where tumour size was not measurable following chemotherapy in 71% of patients. Magnetic resonance imaging had 87.5% sensitivity (95% CI ¼ 68 -97%) and 50% specificity (95% CI ¼ 16 -84%) for a PPV (positive predictive value) of 99.8% and NPV (negative predictive value) of 80% for the detection of residual invasive cancer. Magnetic resonance imaging displayed 80% sensitivity (95% CI ¼ 28.4 -99.5%) and 89% specificity (95% CI ¼ 71 -98%) to detect pathological pCR in the breast. Eighty-four per cent of recruited patients were identified as potentially suitable candidates for BCS following chemotherapy and of those choosing to accept BCS, breast conservation was achieved in 90.5%, or 65.6% of all patients. Of those who proceeded to BCS, 9.5% required a re-do mastectomy because of positive margins; however, no residual tumour was found on histological examination of mastectomy specimens. Magnetic resonance imaging appears to be superior to conventional methods for assessing pathological response and the low rate of re-operation for positive margins indicates a valuable role in aiding the decision to undergo BCS or mastectomy.

Abstract:The selective BRAF inhibitors, vemurafenib and dabrafenib, yield high response rates and improved overall survival in patients with BRAF V600E-mutant metastatic melanoma. Acquired drug resistance and drug toxicity are key challenges when using these drugs. We investigated whether vemurafenib toxicity could successfully be managed with intermittent dosing, and if its therapeutic efficacy could be maintained on intermittent dosing. Six patients with BRAF V600E-mutated metastatic melanoma were treated with an intermittent dosing regimen of vemurafenib. In three patients, toxicities were successfully managed with an intermittent dosing regimen. In the other three patients, intolerable toxicities continued on intermittent dosing. Our experience shows that intermittent dosing can successfully manage vemurafenib toxicities where continuous dosing at a reduced dose does not. Intermittent treatment improves drug tolerability and can achieve or maintain melanoma shrinkage. We recommend that in clinical practice, intermittent dosing should be considered as an alternative to dose reduction/termination in the management of vemurafenib toxicity.

Pancreatic adenocarcinoma has a poor prognosis and frequently develops resistance to standard chemotherapeutics. Oncolytic adenoviruses represent a promising approach to overcome treatment resistance. The replication-selective dl922-947 adenovirus, defective in pRb binding, targets cancers with deregulated cell cycle control, such as the majority of pancreatic tumors. Cell killing efficacy was higher for dl922-947 than for adenovirus type 5 (Ad5) and the clinically approved dl1520 in pancreatic cancer cells with K-ras, p16 and p53 mutations. Combinations of dl922-947 and 5-fluorouracil or gemcitabine (2resulted in strong synergistic cell killing in Suit-2 and the highly drug-and virus-resistant Hs766T cells. Viral uptake increased in response to drugs, but was independent of the expression levels of the viral attachment receptor coxsackie and adenovirus receptor (CAR), whereas expression levels of the internalization receptors a v b 3 -and a v b 5 -integrins were increased. Early viral E1A expression was potently induced with drugs contributing to the synergistic effects. The dl922-947 mutant was more efficacious than Ad5 in vivo in Hs766T and Suit-2 xenograft models. In combination with gemcitabine, median survival was further prolonged. We demonstrate that dl922-947 is highly efficacious in pancreatic cancers and conclude that oncolytic adenoviruses harboring the E1ACR2 deletion have great potential for development into future clinical candidates for pancreatic cancer.

Post-transplant lymphoproliferative disorders (PTLDs)occur in approximately 1% of renal graft recipients. Of these, up to 15 percent are of the T-cell type. In this study, we present four cases of T-cell lymphoma from our renal transplant population, each of whom presented with non-specific symptoms, pancytopenia and/or liver dysfunction, with no obvious lymphadenopathy. They were all diagnosed with rare subsets of T-cell PTLD that included hepato-splenic T-cell lymphoma and anaplastic large cell lymphoma (ALCL). At the time of presentation, the patients were too ill for treatment to be initiated and succumbed to their illness. Increased awareness of this condition may allow for earlier diagnosis and improve its prognosis.