Introduction:
The issue of systemic treatment for early breast cancer in the elderly has always been challenging and in spite of the clear evidence of the potential benefits of adjuvant treatment in ...older women, they are usually undertreated with the potential consequence of worse outcomes.
Areas covered:
This article will review the evidence surrounding the various systemic options in the treatment armamentarium of early-stage breast cancer in elderly patients. The risks and benefits, with particular attention to a number of newly introduced targeted agents, along with the potential role of incorporating a combined geriatric/oncologic assessment as a routine part of the management of elderly patients with breast cancer are considered.
Expert opinion:
Administration of available options for (neo)adjuvant endocrine, chemo, as well as targeted therapeutics in fit elderly patients is feasible and tolerable; however, a routine input from geriatric medicine and psycho-oncology experts as well as the training of specialized oncology staff with special interest in geriatric oncology are believed to improve the outcome of elderly patients.
By focusing on metabolic and morphological tissue properties respectively, FluoroDeoxyGlucose (FDG)-Positron Emission Tomography (PET) and Computed Tomography (CT) modalities include complementary ...and synergistic information for cancerous lesion delineation and characterization (e.g. for outcome prediction), in addition to usual clinical variables. This is especially true in Head and Neck Cancer (HNC). The goal of the HEad and neCK TumOR segmentation and outcome prediction (HECKTOR) challenge was to develop and compare modern image analysis methods to best extract and leverage this information automatically. We present here the post-analysis of HECKTOR 2nd edition, at the 24th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2021. The scope of the challenge was substantially expanded compared to the first edition, by providing a larger population (adding patients from a new clinical center) and proposing an additional task to the challengers, namely the prediction of Progression-Free Survival (PFS). To this end, the participants were given access to a training set of 224 cases from 5 different centers, each with a pre-treatment FDG-PET/CT scan and clinical variables. Their methods were subsequently evaluated on a held-out test set of 101 cases from two centers. For the segmentation task (Task 1), the ranking was based on a Borda counting of their ranks according to two metrics: mean Dice Similarity Coefficient (DSC) and median Hausdorff Distance at 95th percentile (HD95). For the PFS prediction task, challengers could use the tumor contours provided by experts (Task 3) or rely on their own (Task 2). The ranking was obtained according to the Concordance index (C-index) calculated on the predicted risk scores. A total of 103 teams registered for the challenge, for a total of 448 submissions and 29 papers. The best method in the segmentation task obtained an average DSC of 0.759, and the best predictions of PFS obtained a C-index of 0.717 (without relying on the provided contours) and 0.698 (using the expert contours). An interesting finding was that best PFS predictions were reached by relying on DL approaches (with or without explicit tumor segmentation, 4 out of the 5 best ranked) compared to standard radiomics methods using handcrafted features extracted from delineated tumors, and by exploiting alternative tumor contours (automated and/or larger volumes encompassing surrounding tissues) rather than relying on the expert contours. This second edition of the challenge confirmed the promising performance of fully automated primary tumor delineation in PET/CT images of HNC patients, although there is still a margin for improvement in some difficult cases. For the first time, the prediction of outcome was also addressed and the best methods reached relatively good performance (C-index above 0.7). Both results constitute another step forward toward large-scale outcome prediction studies in HNC.
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•The paper describes the second edition of the HECKTOR challenge.•New data (total of 325 cases from 6 centers).•Fully novel task for outcome prediction in synergy with the tumor segmentation task.•Strong participation and high performance (DSC > 0.77, C-index > 0.71).•Various post-challenge analyses, e.g. ranking robustness, ensembling, influence of tumor size on performance.
Micro-Abstract This meta-analysis assessed the risk of encountering selected hair changes in patients with cancer receiving pazopanib. The relative risk of all-grade alopecia and hair color changes ...was 1.75 (95% confidence interval, 1.33-2.31; P < .0001) and 4.54 (95% confidence interval, 3.67-5.62; P < .00001), respectively. Subgroup analyses of hair color changes according to the type of cancer treated revealed significant differences between renal cell carcinoma and non-renal cell carcinoma studies ( P = .01).
Abstract Embryonal tumors with multilayered rosettes (ETMR) are aggressive central nervous system neoplasms with unfavorable prognosis, exhibiting rapid disease progression and frequent ...post-therapeutic relapse. The rarity of ETMR necessitates global collaboration to advance therapies. Radiotherapy (RT) has been associated with improved survival outcomes in ETMR with case series revealing that nearly half of ETMR patients treated without RT relapse within six months of diagnosis. However, RT is often withheld due to young patient age and neurodevelopmental considerations. This high-rate of on-treatment relapse is unique to ETMR and suggests that radiation-sparing regimens may be suboptimal. PNOC031 is an international collaboration, establishing a global clinical trial to innovate and improve therapeutic interventions for children with ETMR. Eligible patients with newly-diagnosed ETMR are stratified into three cohorts: Cohort 1 - gross total resection/RT-eligible patients to receive early focal radiotherapy (RT); Cohort 2 – gross total resection/not RT-eligible to receive high-dose chemotherapy with autologous stem cell rescue; and Cohort 3 – less than gross total resection or with metastatic disease to receive RT or high-dose chemotherapy per RT eligibility, based on age and tumor location. Cohort 1 will test the hypothesis if early RT improves outcomes in a pilot cohort of 20 patients. Patients will receive six weeks of induction chemotherapy, followed by focal irradiation and an additional six weeks of chemotherapy. Six-month progression-free survival will be assessed to determine the impact of radiotherapy on the rate of early relapse. Cohorts 2 and 3 will allow collection of uniform prospective clinical data using a common treatment backbone, to inform future clinical trial design for ETMR. Incorporating a myriad of correlative studies, including next-generation sequencing, cerebrospinal fluid analyses, microbiome profiles, and evaluations of social determinants of health alongside cognitive outcomes, will enhance comprehensive understanding of clinical responses and advance therapeutic options for this high risk disease.
Abstract
Background
Clinical predictors of local recurrence following radiation among patients with brain metastases (BrM) provide limited explanatory power. We developed a DNA-based signature of ...radiotherapeutic efficacy among patients with BrM to better characterize recurrence risk.
Methods
We identified 570 patients with 1487 BrM managed with whole-brain (WBRT) or stereotactic radiation therapy at Brigham and Women’s Hospital/Dana-Farber Cancer Institute (2013–2020) for whom next-generation sequencing panel data (OncoPanel) were available. Fine/Gray’s competing risks regression was utilized to compare local recurrence on a per-metastasis level among patients with versus without somatic alterations of likely biological significance across 84 genes. Genes with a q-value ≤ 0.10 were utilized to develop a “Brain-Radiation Prediction Score” (“Brain-RPS”).
Results
Genomic alterations in 11 (ATM, MYCL, PALB2, FAS, PRDM1, PAX5, CDKN1B, EZH2, NBN, DIS3, and MDM4) and 2 genes (FBXW7 and AURKA) were associated with decreased or increased risk of local recurrence, respectively (q-value ≤ 0.10). Weighted scores corresponding to the strength of association with local failure for each gene were summed to calculate a patient-level RPS. On multivariable Fine/Gray’s competing risks regression, RPS 1.66 (1.44–1.91, P < .001), metastasis-associated edema 1.60 (1.16–2.21), P = .004, baseline size 1.02 (1.01–1.03), P < .001 and receipt of WBRT without local therapy 4.04 (2.49–6.58), P < .001 were independent predictors of local failure.
Conclusions
We developed a genomic score to quantify local recurrence risk following brain-directed radiation. To the best of our knowledge, this represents the first study to systematically correlate DNA-based alterations with radiotherapeutic outcomes in BrM. If validated, Brain-RPS has potential to facilitate clinical trials aimed at genome-based personalization of radiation in BrM.
This meta-analysis was conducted aiming at assessing the risk of selected dermatological toxicities associated with MEK inhibitors.
We considered relevant prospective randomized Phase II and III ...trials of cancer patients on the three MEK inhibitors (trametinib, selumetinib and cobimetinib), describing events of skin rash and acneiform dermatitis, as eligible for inclusion.
After exclusion of ineligible studies, a total of 14 clinical trials were considered eligible for the meta-analysis. The relative risk of all-grade skin rash and acneiform dermatitis was 1.71 (95% CI: 1.07-2.72; p = 0.02) and 6.55 (95% CI: 3.42-12.56; p < 0.00001), correspondingly; while the relative risk of high-grade skin rash and acneiform dermatitis was 2.64 (95% CI: 1.42-4.91; p = 0.002) and 8.44 (95% CI: 2.39-29.81; p = 0.0009), respectively.
Our meta-analysis has demonstrated that MEK inhibitor-based treatment is associated with an increased risk of all-grade and high-grade skin rash and acneiform dermatitis compared with control.
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Background: Short-course radiation therapy (SCRT) has been studied in European trials but is not often utilized in the US. We aim to describe the utilization and outcomes of SCRT ...compared to the more widely used long-course (LCRT) neoadjuvant regimen. Methods: The National Cancer Database (NCDB) was queried for patients treated with preoperative RT followed by surgical resection for non-metastatic rectal adenocarcinoma from 2004-2014. Patient, tumor and treatment-related characteristics were compared between those treated with SCRT (defined as patients receiving < 26 Gray (Gy) in < 7 fractions) and those treated with LCRT. Survivals were compared using the Log-Rank test. Univariate and multivariate Cox regression analyses were used for univariate analysis of factors associated with overall survival (OS). Results: 48898 patients were included for analysis: 48396 patients (99.0%) treated with LCRT and 502 (1.0%) treated with SCRT. Patients treated with SCRT were older (median range age 67 21-90 vs 60 18-90; p < .001), had more comorbidities (Charlson/Deyo score 1+ N = 155 (30.9%) vs N = 9795 (20.2%); p < .001), had earlier T-stage (T1-2 N = 141 (28.1%) vs N = 5774 (11.9%); p < .001) and were more likely to be clinically node-negative (N = 324 (64.5%) vs N = 22701 (46.9%); p < .001). Patients treated with SCRT were more likely to be treated after 2009 (N = 303 (60.4%) vs N = 24834 (51.3%); p < .001) and were more often treated at an academic center (N = 318 (63.3%) vs N = 20375 (42.1%); p < .001). Patients treated with SCRT had a 2- and 5-year OS of 85.8% and 65.7%, respectively, compared with 90.9% and 73.5% in patients treated with LCRT (log-rank p < .001). On univariate analysis, receipt of SCRT was associated with worse OS (HR 1.40 95% CI 1.18-1.65; p < .001). However, when entered into a multivariate model including other patient and tumor-related factors, SCRT was actually associated with improved OS (HR 0.77 95% CI 0.59-1.00; p = .048). Conclusions: SCRT is utilized for approximately 1% of patients treated with preoperative treatment of non-metastatic rectal cancer in the US. The results of recently completed randomized trials may further inform patterns of practice in the US and abroad.
Background: We performed a meta-analysis of the risk of oral and gastrointestinal (GI) mucosal injury associated with S-1-based regimens.
Patients and methods: Randomized phase II and III trials of ...patients with solid tumors on S-1; describing events of all-grade and high-grade stomatitis and diarrhea constituted the eligible studies.
Results: After exclusion of ineligible studies, a total of 26 clinical trials were considered eligible for the meta-analysis. The odds ratio (OR) of all-grade and high-grade stomatitis for S-1 vs. non-fluoropyrimidine controls was 4.39 95% CI: 1.05, 18.37; p = 0.04 and 5.64 95% CI: 1.46, 21.77; p = 0.01, respectively; while the OR of all-grade and high-grade stomatitis for S-1 vs. infusional 5-fluorouracil (5-FU) control was −1.01 95% CI: 0.22, 4.63; p = 0.99 and 0.32 95% CI: 0.20, 0.49; p < 0.00001, respectively. The OR of all-grade and high-grade diarrhea for S-1 vs. non-fluoropyrimidine controls was 2.48 95% CI: 2.12, 2.90; p < 0.00001 and 1.95 95% CI: 1.29, 2.96; p = 0.002, respectively; while the OR of all-grade and high-grade diarrhea for S-1 vs. infusional 5-FU control was −1.03 95% CI: 0.87, 1.22; p = 0.76 and 2.52 95% CI: 1.80, 3.52; p < 0.00001, respectively. Conclusions: Compared to non-fluoropyrimidine control, patients treated with S-1-based regimens have an increased risk of all-grade and high-grade stomatitis and diarrhea; while on the other hand, patients treated with infusional 5-FU have a greater risk of high-grade stomatitis and diarrhea compared to patients treated with S-1-based regimens.
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