8 research outputs found
A phase II study of sequential neoadjuvant gemcitabine plus doxorubicin followed by gemcitabine plus cisplatin in patients with operable breast cancer: prediction of response using molecular profiling
This study examined the pathological complete response (pCR) rate and safety of sequential gemcitabine-based combinations in breast cancer. We also examined gene expression profiles from tumour biopsies to identify biomarkers predictive of response. Indian women with large or locally advanced breast cancer received 4 cycles of gemcitabine 1200âmgâmâ2 plus doxorubicin 60âmgâmâ2 (Gem+Dox), then 4 cycles of gemcitabine 1000âmgâmâ2 plus cisplatin 70âmgâmâ2 (Gem+Cis), and surgery. Three alternate dosing sequences were used during cycle 1 to examine dynamic changes in molecular profiles. Of 65 women treated, 13 (24.5% of 53 patients with surgery) had a pCR and 22 (33.8%) had a complete clinical response. Patients administered Gem d1, 8 and Dox d2 in cycle 1 (20 of 65) reported more toxicities, with G3/4 neutropenic infection/febrile neutropenia (7 of 20) as the most common cycle-1 event. Four drug-related deaths occurred. In 46 of 65 patients, 10-fold cross validated supervised analyses identified gene expression patterns that predicted with ⊞73% accuracy (1) clinical complete response after eight cycles, (2) overall clinical complete response, and (3) pCR. This regimen shows strong activity. Patients receiving Gem d1, 8 and Dox d2 experienced unacceptable toxicity, whereas patients on other sequences had manageable safety profiles. Gene expression patterns may predict benefit from gemcitabine-containing neoadjuvant therapy
Ethnic minority disparities in progression and mortality of pre-dialysis chronic kidney disease : a systematic scoping review
Background: There are a growing number of studies on ethnic differences in progression and mortality for pre-dialysis chronic kidney disease (CKD), but this literature has yet to be synthesised, particularly for studies on mortality. Methods: This scoping review synthesized existing literature on ethnic differences in progression and mortality for adults with pre-dialysis CKD, explored factors contributing to these differences, and identified gaps in the literature. A comprehensive search strategy using search terms for ethnicity and CKD was taken to identify potentially relevant studies. Nine databases were searched from 1992 to June 2017, with an updated search in February 2020. Results: 8059 articles were identified and screened. Fifty-five studies (2 systematic review, 7 non-systematic reviews, and 46 individual studies) were included in this review. Most were US studies and compared African-American/Afro-Caribbean and Caucasian populations, and fewer studies assessed outcomes for Hispanics and Asians. Most studies reported higher risk of CKD progression in Afro-Caribbean/African-Americans, Hispanics, and Asians, lower risk of mortality for Asians, and mixed findings on risk of mortality for Afro-Caribbean/African-Americans and Hispanics, compared to Caucasians. Biological factors such as hypertension, diabetes, and cardiovascular disease contributed to increased risk of progression for ethnic minorities but did not increase risk of mortality in these groups. Conclusions: Higher rates of renal replacement therapy among ethnic minorities may be partly due to increased risk of progression and reduced mortality in these groups. The review identifies gaps in the literature and highlights a need for a more structured approach by researchers that would allow higher confidence in single studies and better harmonization of data across studies to advance our understanding of CKD progression and mortality
Prevalence and progression of diabetic nephropathy in South Asian, white European and African Caribbean people with type 2 diabetes: A systematic review and meta-analysis
AIMS: To conduct a systematic review and meta-analysis of published observational evidence to assess the difference in the prevalence and progression of diabetic nephropathy, and the development of end-stage renal disease (ESRD) in people from three different ethnic groups with type 2 diabetes (T2DM). MATERIALS AND METHODS: Relevant studies were identified in a literature search of MEDLINE, EMBASE and reference lists of relevant studies published up to May 2018. We decided a priori that there were no differences in the prevalence and progression of diabetic nephropathy, and the development of ESRD in the three ethnicities with T2DM. Pooled relative risks of microalbuminuria by ethnicity were estimated by fitting three random effects meta-analyses models. A narrative synthesis of the nephropathy progression in the studies was carried out. The review was registered in PROSPERO (CRD42018107350). RESULTS: Thirty-two studies with data on 153â827 unique participants were eligible for inclusion in the review. The pooled prevalence ratio of microalbuminuria in South Asian compared with white European participants was 1.14 (95% confidence interval [CI] 0.99, 1.32; Pâ=â0.065), while for African Caribbean vs South Asian participants the pooled prevalence ratio was 1.08 (95% CI 0.93, 1.24; Pâ=â0.327). Results for renal decline were inconsistent, with preponderance towards a high rate of disease progression in South Asian compared with white participants. The estimated pooled incidence rate ratio (IRR) for ESRD was significantly higher in African Caribbean vs white European participants: 2.75 (95% CI 2.01, 3.48; Pâ<â0.001). CONCLUSION: The results of this review did not show a significant link between ethnicity (South Asian, white European and African Caribbean) and the prevalence of microalbuminuria; however, the IRR for ESRD in African Caribbean compared with white European participants was significantly higher. Further research is needed to explore the potential non-albuminuric pathways of progression to ESRD
Immediate breast reconstruction surgery using implants and autologous lower dermal sling procedure may mitigate radiation therapy complications
Dose escalation in image-guided, intensity-modulated radiotherapy of carcinoma prostate: Initial experience in India
Background : Increasing incidence and significant stage migration from
distant metastases to a localized disease, due to screening application
of PSA, is taking place in carcinoma prostate. Also, role of
radiotherapy is increasing in carcinoma prostate due to rapid strides
in technology. Aim: The present retrospective study, evaluates
escalating the dose in the treatment of localized carcinoma prostate
using integration of multiple advanced techniques. Settings and Design:
The settings designed are: a) use of gold seed internal fiducial
markers: b) clinical application of emerging Megavoltage Cone Beam
Computed Tomography (MVCBCT) technology for Image Guided Radiotherapy
(IGRT); c) Intensity Modulated Radiotherapy (IMRT); d) adopting
biochemical method for follow-up. Methods and Material: Twelve
consecutive, biopsy proven localized cancer of prostate patients,
treated with dose escalation IMRT& IGRT protocol between August
2006 and January 2008, were analyzed. Gold seed markers in prostate
were used for daily localization with MVCBCT or Electronic Portal
Imaging (EPI). All patients underwent clinical and biochemical
follow-up. Statistical Analysis& Results : Planned dose of 7740 cGy
was delivered in 10 out of 12 patients (83%). While one patient had
migration of maximum of 3 mm, two others had 1 mm migration of one seed
during course of treatment. One patient (8%) developed Grade II
proctitis at 12th month. During the mean follow-up duration of 12.2
months, 92% (11/12) had biochemical control within 3 months of
treatment. Conclusions: IGRT technique using MVCBCT for implanted
fiducial gold seed localization was feasible for IMRT dose escalation
in carcinoma prostate with excellent results
Dose escalation in image-guided, intensity-modulated radiotherapy of carcinoma prostate: Initial experience in India
Background : Increasing incidence and significant stage migration from
distant metastases to a localized disease, due to screening application
of PSA, is taking place in carcinoma prostate. Also, role of
radiotherapy is increasing in carcinoma prostate due to rapid strides
in technology. Aim: The present retrospective study, evaluates
escalating the dose in the treatment of localized carcinoma prostate
using integration of multiple advanced techniques. Settings and Design:
The settings designed are: a) use of gold seed internal fiducial
markers: b) clinical application of emerging Megavoltage Cone Beam
Computed Tomography (MVCBCT) technology for Image Guided Radiotherapy
(IGRT); c) Intensity Modulated Radiotherapy (IMRT); d) adopting
biochemical method for follow-up. Methods and Material: Twelve
consecutive, biopsy proven localized cancer of prostate patients,
treated with dose escalation IMRT& IGRT protocol between August
2006 and January 2008, were analyzed. Gold seed markers in prostate
were used for daily localization with MVCBCT or Electronic Portal
Imaging (EPI). All patients underwent clinical and biochemical
follow-up. Statistical Analysis& Results : Planned dose of 7740 cGy
was delivered in 10 out of 12 patients (83%). While one patient had
migration of maximum of 3 mm, two others had 1 mm migration of one seed
during course of treatment. One patient (8%) developed Grade II
proctitis at 12th month. During the mean follow-up duration of 12.2
months, 92% (11/12) had biochemical control within 3 months of
treatment. Conclusions: IGRT technique using MVCBCT for implanted
fiducial gold seed localization was feasible for IMRT dose escalation
in carcinoma prostate with excellent results
Text mining and word embedding for classification of decision making variables in breast cancer surgery
Introduction: Decision making in surgical oncology of the breast has increased its complexity over the last twenty years. This Delphi survey investigates the opinion of an expert panel about the decision making process in surgical procedures on the breast for oncological purposes. Methods: Twenty-seven experts were invited to partake into a Delphi Survey. At the first round they have been asked to provide a list of features involved in the decision making process (patient's characteristics; disease characteristics; surgical techniques, outcomes) and comment on it. Using text-mining techniques we extracted a list of mono-bi-trigrams potentially representative of decision drivers. A technique of ânatural language processingâ called Word2vec was used to validate changes to texts using synonyms and plesionyms. Word2Vec was also used to test the semantic relevance of n-grams within a corpus of knowledge made up of books edited by panel members. The final list of variables extracted was submitted to the judgement of the panel for final validation at the second round of the Delphi using closed ended questions. Results: 52 features out of 59 have been approved by the panel. The overall consensus was 87.1% Conclusions: Text mining and natural language processing allowed the extraction of a number of decision drivers and outcomes as part of the decision making process in surgical oncology on the breast. This result was obtained transforming narrative texts into structured data. The high level of consensus among experts provided validation to this process