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NPJ Precision Oncology Jun 2024Cancer is the second most common cause of death in children aged 1-14 years in the United States, with 11,000 new cases and 1200 deaths annually. Pediatric cancers...
Cancer is the second most common cause of death in children aged 1-14 years in the United States, with 11,000 new cases and 1200 deaths annually. Pediatric cancers typically have lower mutational burden compared to adult-onset cancers, however, the epigenomes in pediatric cancer are highly altered, with widespread DNA methylation changes. The rarity of pediatric cancers poses a significant challenge to developing cancer-type specific biomarkers for diagnosis, prognosis, or treatment monitoring. In the current study, we explored the potential of a DNA methylation profile common across various pediatric cancers. To do this, we conducted whole genome bisulfite sequencing (WGBS) on 31 recurrent pediatric tumor tissues, 13 normal tissues, and 20 plasma cell-free (cf)DNA samples, representing 11 different pediatric cancer types. We defined minimal focal regions that were differentially methylated across samples in the multiple cancer types which we termed minimally differentially methylated regions (mDMRs). These methylation changes were also observed in 506 pediatric and 5691 adult cancer samples accessed from publicly available databases, and in 44 pediatric cancer samples we analyzed using a targeted hybridization probe capture assay. Finally, we found that these methylation changes were detectable in cfDNA and could serve as potential cfDNA methylation biomarkers for early detection or minimal residual disease.
PubMed: 38824198
DOI: 10.1038/s41698-024-00590-1 -
Nature Communications May 2024Patient-derived xenograft (PDX) models are widely used in cancer research. To investigate the genomic fidelity of non-small cell lung cancer PDX models, we established...
Patient-derived xenograft (PDX) models are widely used in cancer research. To investigate the genomic fidelity of non-small cell lung cancer PDX models, we established 48 PDX models from 22 patients enrolled in the TRACERx study. Multi-region tumor sampling increased successful PDX engraftment and most models were histologically similar to their parent tumor. Whole-exome sequencing enabled comparison of tumors and PDX models and we provide an adapted mouse reference genome for improved removal of NOD scid gamma (NSG) mouse-derived reads from sequencing data. PDX model establishment caused a genomic bottleneck, with models often representing a single tumor subclone. While distinct tumor subclones were represented in independent models from the same tumor, individual PDX models did not fully recapitulate intratumor heterogeneity. On-going genomic evolution in mice contributed modestly to the genomic distance between tumors and PDX models. Our study highlights the importance of considering primary tumor heterogeneity when using PDX models and emphasizes the benefit of comprehensive tumor sampling.
Topics: Carcinoma, Non-Small-Cell Lung; Humans; Animals; Lung Neoplasms; Mice; Mice, Inbred NOD; Mice, SCID; Genetic Heterogeneity; Female; Exome Sequencing; Genomics; Male; Xenograft Model Antitumor Assays; Heterografts; Disease Models, Animal; Aged; Middle Aged
PubMed: 38821942
DOI: 10.1038/s41467-024-47547-3 -
PloS One 2024Breast cancer remains a critical global concern, underscoring the urgent need for early detection and accurate diagnosis to improve survival rates among women. Recent...
Breast cancer remains a critical global concern, underscoring the urgent need for early detection and accurate diagnosis to improve survival rates among women. Recent developments in deep learning have shown promising potential for computer-aided detection (CAD) systems to address this challenge. In this study, a novel segmentation method based on deep learning is designed to detect tumors in breast ultrasound images. Our proposed approach combines two powerful attention mechanisms: the novel Positional Convolutional Block Attention Module (PCBAM) and Shifted Window Attention (SWA), integrated into a Residual U-Net model. The PCBAM enhances the Convolutional Block Attention Module (CBAM) by incorporating the Positional Attention Module (PAM), thereby improving the contextual information captured by CBAM and enhancing the model's ability to capture spatial relationships within local features. Additionally, we employ SWA within the bottleneck layer of the Residual U-Net to further enhance the model's performance. To evaluate our approach, we perform experiments using two widely used datasets of breast ultrasound images and the obtained results demonstrate its capability in accurately detecting tumors. Our approach achieves state-of-the-art performance with dice score of 74.23% and 78.58% on BUSI and UDIAT datasets, respectively in segmenting the breast tumor region, showcasing its potential to help with precise tumor detection. By leveraging the power of deep learning and integrating innovative attention mechanisms, our study contributes to the ongoing efforts to improve breast cancer detection and ultimately enhance women's survival rates. The source code of our work can be found here: https://github.com/AyushRoy2001/DAUNet.
Topics: Humans; Breast Neoplasms; Female; Deep Learning; Ultrasonography, Mammary; Neural Networks, Computer; Algorithms; Image Interpretation, Computer-Assisted; Breast; Image Processing, Computer-Assisted
PubMed: 38820462
DOI: 10.1371/journal.pone.0303670 -
Cancer Medicine Jun 2024En-Bloc transurethral resection of bladder tumor (ERBT) was clinically used to resect non-muscle-invasive bladder cancer (NMIBC). However, discrepancies persist... (Meta-Analysis)
Meta-Analysis Review Comparative Study
BACKGROUND
En-Bloc transurethral resection of bladder tumor (ERBT) was clinically used to resect non-muscle-invasive bladder cancer (NMIBC). However, discrepancies persist regarding the comparisons between ERBT and conventional transurethral resection of bladder tumor (cTURBT).
METHODS
We conducted a comprehensive search in PubMed, Embase, Web of Science, Cochrane Database of Systematic Reviews, and performed manual searches of reference lists to collect and extract data. Data evaluation was carried out using Review Manager 5.4.0, Rx64 4.1.3, and relevant packages.
RESULTS
There were nine eligible meta-analyses and nine eligible RCTs in our study. NMIBC patients undergoing ERBT were significant associated with a lower rate of bladder perforation and obturator nerve reflex compared to those receiving cTURBT. Our pooled result indicated that ERBT and cTURBT required similar operation time. Regarding postoperative outcomes, ERBT demonstrated superior performance compared to cTURBT in terms of detrusor muscle presence, catheterization time, and residual tumor. ERBT exhibited a higher rate of three-month recurrence-free survival (RFS) compared to those receiving cTURBT (p < 0.05; I = 0%). In bipolar subgroup, ERBT had a significant better 12-month RFS than cTURBT (p < 0.05; I = 0%). Simultaneously, the exclusion of Hybrid Knife data revealed a significant improvement in 12-month RFS associated with ERBT (p < 0.05; I = 50%).
CONCLUSION
Using a combination of umbrella review and meta-analysis, we demonstrated that ERBT had better or comparable perioperative outcome and improved 3 and 12 month RFS than cTURBT. We suggest that ERBT maybe a better surgical method for patients with NMIBC compared with cTURBT.
Topics: Humans; Urinary Bladder Neoplasms; Cystectomy; Treatment Outcome; Urethra; Neoplasm Invasiveness; Non-Muscle Invasive Bladder Neoplasms
PubMed: 38819629
DOI: 10.1002/cam4.7323 -
Indian Journal of Nuclear Medicine :... 2024Thyroid cancer is the most common endocrine malignant tumor and accounts for 1% of all cancers. Management of differentiated thyroid carcinoma is total thyroidectomy,...
Thyroid cancer is the most common endocrine malignant tumor and accounts for 1% of all cancers. Management of differentiated thyroid carcinoma is total thyroidectomy, followed by iodine-131 (I-131) radioactive iodine (RAI) therapy for thyroid remnant tissue. I-131 whole-body scan helps in the follow-up evaluation in remnant, residual, and recurrence cases. Principle of uptake of I-131 is through sodium-iodide symporter expression on the cells. Physiological uptake of iodine is usually seen in salivary glands and gastrointestinal tract, and false-positive uptakes are seen in lesions such as mucinous cystadenoma, struma ovarii, hepatic, renal, thymic, and meibomian cysts. Here, we present the review of literature of series of cases observed in our department presenting with false-positive uptake of RAI in vertebral hemangioma, lipoma, sinusitis, teratoma, and uterine leiomyoma.
PubMed: 38817715
DOI: 10.4103/ijnm.ijnm_96_23 -
Cureus Apr 2024The aim of this retrospective, observational, descriptive study was to identify predictors of response to neoadjuvant therapy in breast cancer patients and to validate...
Predictive Factors of Neoadjuvant Chemotherapy Response in Breast Cancer Validated by Three Anatomopathological Scores: Residual Cancer Burden, Chevallier System, and Tumor-Infiltrating Lymphocytes.
INTRODUCTION
The aim of this retrospective, observational, descriptive study was to identify predictors of response to neoadjuvant therapy in breast cancer patients and to validate them using three anatomopathological scores, such as residual cancer burden (RCB) score, Chevallier system, and tumor-infiltrating lymphocytes (TIL) score.
MATERIALS AND METHODS
We conducted a study on 88 female patients aged 37 to 78 years with confirmed breast cancer who were indicated for neoadjuvant chemotherapy. We analyzed different individual variables (such as age, menarche, and menopause), clinical/imaging characteristics of the breast tumor and axillary nodes, immunohistochemical biomarkers (such as ER/PR/HER2 and Ki67), and histopathological features (such as subtype and grading) in relation to three anatomopathological scores calculated based on the surgical resection specimen.
RESULTS
The percentage of patients who could have benefited from conservative surgery increased from 6% at the time of diagnosis to 20% post-primary systemic therapy (PST). Age under 49 (p = 0.01), premenopausal status (p < 0.01), no special type (NST) (p = 0.04), high Ki67 (p < 0.01), triple-negative breast cancer (TNBC) (p = 0.02) are positive predictive factors of neoadjuvant therapy, while lobular/mixt carcinoma-type (p = 0.04), luminal A (p = 0.01), positive lymph node (p < 0.01), and low differentiation grade (p = 0.01) are negative predictive factors for the response to PST.
CONCLUSION
There is a strong correlation between the RCB score and the Chevallier system for quantifying the response to PST, with most predictive factors being confirmed through appropriate statistical analysis for both. TIL score values correlated with only some of the predictors, most likely due to the importance of calculating this score on both biopsy specimens at diagnosis and resection specimens after chemotherapy.
PubMed: 38817506
DOI: 10.7759/cureus.59391 -
International Journal of Hyperthermia :... 2024The treatment of recurrent thyroid cancer with critical organ invasion is challenging. The combination of radiofrequency ablation (RFA) and external beam radiation...
PURPOSE
The treatment of recurrent thyroid cancer with critical organ invasion is challenging. The combination of radiofrequency ablation (RFA) and external beam radiation therapy (EBRT) has been proposed as an effective option. This study evaluates outcomes for inoperable residual/recurrent differentiated thyroid cancer (rDTC) patients treated with RFA followed by EBRT.
MATERIALS AND METHODS
Patients with rDTC treated with RFA followed by EBRT were retrospectively studied. RFA was performed using a free-hand, 'moving-shot' technique under US or CT guidance. For lesions invading critical structures intolerant to 'en bloc' high-temperature RFA, limited-field EBRT using 6- or 10-MV photons was used for adjuvant treatment at a dose of 66 Gy in 33 daily fractions. Toxicities and outcomes were reviewed.
RESULTS
Between April 2020 and January 2022, 11 patients with 14 rDTC lesions underwent RFA followed by EBRT. Five patients had metastatic lesions at rDTC diagnosis. With a median follow-up period of 33.7 months, all patients maintained locoregional control, while achieving a 2-year survival rate of 90.9%. This combined treatment achieved a volume reduction ratio of 92.1% ± 5.1%. The mean nadir thyroglobulin level in patients without initial distant metastases after treatment was 1.40 ± 0.81 ng/ml. Regarding treatment-related complications, one patient (9%) experienced temporary hoarseness after RFA, grade 2 radiation dermatitis occurred in 3 patients (27.2%), and grade 2 dysphagia was noted in 4 patients (36.4%). No grade 3 or greater toxicities occurred.
CONCLUSIONS
Salvage RFA followed by EBRT is feasible, effective and safe for patients with rDTC.
Topics: Humans; Thyroid Neoplasms; Male; Female; Middle Aged; Radiofrequency Ablation; Adult; Aged; Salvage Therapy; Retrospective Studies; Neoplasm Recurrence, Local
PubMed: 38816274
DOI: 10.1080/02656736.2024.2358054 -
Breast (Edinburgh, Scotland) May 2024Neoadjuvant chemotherapy (NACT) is widely used in the treatment of triple-negative and HER2-positive breast cancer (BC), but its use in estrogen receptor (ER) and/or...
BACKGROUND
Neoadjuvant chemotherapy (NACT) is widely used in the treatment of triple-negative and HER2-positive breast cancer (BC), but its use in estrogen receptor (ER) and/or progesterone receptor (PR) positive/HER2-negative BC is questioned because of the low pathologic complete response (pCR) rates. This retrospective study assessed the mRNA-based MammaTyper® assay's capability of predicting pCR with NACT, and ER, PR, Ki67, and HER2 status at immunohistochemical (IHC) through transcriptomics.
METHODS
Diagnostic biopsies from 76 BC patients treated at the Cremona Hospital between 2012-2018 were analyzed. Relative mRNA expression levels of ERBB2, ESR1, PGR, and MKI67 were measured using the MammaTyper® kit and integrated into a pCR score. Predicting capability of pCR and standard IHC biomarkers could be assessed with ROC curves in 75 and 76 patients, respectively.
RESULTS
Overall, 68.0% patients obtained a MammaTyper® high-score and 32.0% a MammaTyper® low-score. Among high-score patients, 62.7% achieved pCR, compared to 16.7% in the low-score group (p = 0.0003). The binary MammaTyper® score showed good prediction of pCR in the overall cohort (area under curve [AUC] = 0.756) and in HR+/HER2-negative cases (AUC = 0.774). In cases with residual disease, the continuous MammaTyper® score correlated moderately with residual tumor size and decrease in tumor size. MammaTyper® showed substantial agreement with IHC for ESR1/ER and ERBB2/HER2, and moderate agreement for PGR/PR and MKI67/Ki67.
CONCLUSION
Overall, MammaTyper® pCR score may serve as a standardized tool for predicting NACT response in HR+/HER2-negative BC, potentially guiding treatment strategies. Additionally, it could provide a more standardized and reproducible assessment of ER, PR, HER2, and Ki67 status.
PubMed: 38815444
DOI: 10.1016/j.breast.2024.103753 -
American Society of Clinical Oncology... Jun 2024The management of axillary lymph nodes in breast cancer is continually evolving. Recent data now support omitting axillary lymph node dissection (ALND) in most patients... (Review)
Review
Personalizing Locoregional Therapy in Patients With Breast Cancer in 2024: Tailoring Axillary Surgery, Escalating Lymphatic Surgery, and Implementing Evidence-Based Hypofractionated Radiotherapy.
The management of axillary lymph nodes in breast cancer is continually evolving. Recent data now support omitting axillary lymph node dissection (ALND) in most patients with metastases in up to two sentinel lymph nodes (SLNs) during upfront surgery and those with residual isolated tumor cells after neoadjuvant chemotherapy (NACT). In the upfront surgery setting, ALND is still indicated, however, in patients with clinically node-positive breast cancer or more than two positive SLNs and, after NACT, in case of residual micrometastases and macrometastases. Omission of the sentinel lymph node biopsy (SLNB) can be considered in many postmenopausal patients with small luminal breast cancer, particularly when axillary ultrasound is negative. Several randomized controlled trials (RCTs) are currently aiming at eliminating the remaining indications for ALND and also establishing omission of SLNB in a broader patient population. The movement to deescalate axillary staging is in part because of the association between ALND and lymphedema, which is swelling of an extremity because of lymphatic damage and obstructed lymphatic drainage. To reduce the risk of developing this condition, patients undergoing ALND can undergo reverse mapping of the axilla and immediate reconstruction or bypass of the lymphatics from the involved extremity. Decongestion and compression are the foundation of conservative treatment for established lymphedema, while lymphovenous bypass and lymph node transfer are surgical procedures to address the physiologic dysfunction. Radiotherapy is an essential component of breast locoregional therapy: more than three decades of radiation research has optimized treatment according to patient's risk of local recurrence while substantially reducing the number of treatment visits. High-quality RCTs have shown the efficacy and safety of hypofractionation-more than 2Gy radiation dose per treatment (fraction)-significantly reducing the burden of radiotherapy treatment for many patients with breast cancer. In 2024, guidelines recommend no more than 15-16 fractions for whole-breast and nodal radiotherapy, with some recommending five fractions for whole-breast radiotherapy. In addition, simultaneous integrated boost (SIB) has been shown to be noninferior to sequential boost with regards to ipsilateral breast tumor recurrence with similar or reduced long-term side effects, also reducing overall treatment length. Further RCTs are underway investigating other indications for five fractions, including SIB and regional node irradiation, such that, in future, it may be possible for the majority of breast radiotherapy patients to be treated with a 1-week course. This manuscript serves to outline the latest updates on axillary surgical staging, lymphatic surgery, and evidence-based radiotherapy in the treatment of breast cancer.
Topics: Humans; Breast Neoplasms; Female; Axilla; Lymph Node Excision; Radiation Dose Hypofractionation; Lymphatic Metastasis; Sentinel Lymph Node Biopsy; Combined Modality Therapy; Lymph Nodes; Neoplasm Staging; Neoadjuvant Therapy
PubMed: 38815195
DOI: 10.1200/EDBK_438776 -
Breast Cancer Research and Treatment Aug 2024Breast cancer remains the most commonly diagnosed cancer in women. Breast-conserving surgery (BCS) is the standard approach for small low-risk tumors. If the efficacy of...
BACKGROUND
Breast cancer remains the most commonly diagnosed cancer in women. Breast-conserving surgery (BCS) is the standard approach for small low-risk tumors. If the efficacy of cryoablation is demonstrated, it could provide a minimally invasive alternative to surgery.
PURPOSE
To determine the success of ultrasound-guided cryoablation in achieving the absence of Residual Invasive Cancer (RIC) for patients with ER + /HER2- tumors ≤ 2cm and sonographically negative axillary nodes.
MATERIALS AND METHODS
This prospective study was carried out from April 2021 to June 2023, and involved 60 preoperative cryoablation procedures on ultrasound-visible, node-negative (cN0) infiltrating ductal carcinomas (IDC). Standard diagnostic imaging included mammography and tomosynthesis, supplemented by ultrasound-guided biopsy. MRI was performed in patients with associated intraductal carcinoma (DCIS) and an invasive component on core needle biopsy (18 out of 22 cases). All tumors were tagged with ferromagnetic seeds. A triple-phase protocol (freezing-thawing-freezing) with Argon was used, with an average procedure duration of 40 min. A logistic regression model was applied to determine significant correlation between RIC and the study variables.
RESULTS
Fifty-nine women (mean age 63 ± 8 years) with sixty low-risk unifocal IDC underwent cryoablation prior to surgery. Pathological examination of lumpectomy specimens post-cryoablation revealed RIC in only one of 38 patients with pure IDC and in 4 of 22 mixed IDC/DCIS cases. All treated tumors had clear surgical margins, with no significant procedural complications.
CONCLUSIONS
Cryoablation was effective in eradicating 97% of pure infiltrating ER + /HER2-tumors ≤ 2cm, demonstrating its potential as a surgical alternative in selected patients.
Topics: Humans; Female; Cryosurgery; Breast Neoplasms; Middle Aged; Aged; Receptor, ErbB-2; Prospective Studies; Prognosis; Neoplasm, Residual; Adult; Receptors, Estrogen; Carcinoma, Ductal, Breast; Mastectomy, Segmental; Aged, 80 and over; Preoperative Care
PubMed: 38814508
DOI: 10.1007/s10549-024-07325-7