An osteoporotic hip fracture in a 14-year-old girl undergoing chemotherapy and operated for knee osteosarcoma

Non-weight-bearing, pre- and postsurgical immobilization, neoadjuvant and adjuvant chemotherapy are known to act on bone turnover, causing osteoporosis over short and long time periods. Treatment of fracture insurgence is very difficult because it really depends on being able to choose the right time (i.e., when immunodeficiency is less important). We report a case of spontaneous neck femur fracture during adjuvant chemotherapy in a young girl treated with resection and prosthesis reconstruction for distal femur osteosarcoma. Possible prevention and the correct approach and surgical timing are emphasized considering immunodeficiency following chemotherapy

Re: Mastectomy and oophorectomy by menstrual cycle phase in women with operable breast cancer

No abstract availabl

PET scanning evaluation of response to imatinib mesylate therapy in gastrointestinal stromal tumor (GIST) patients

Background: Unresectable or metastatic gastrointestinal stromal tumors (GISTs) exhibit a dynamic clinical course, with no evidence of benefit from any standard cytotoxic chemotherapy and an inevitably fatal outcome. With the introduction of Imatinib, an oral drug able to inhibit the KIT receptor tyrosine kinase, new questions arise regarding our ability to monitor treatment response with conventional methods and optimally manage such patients on treatment with new agents. Materials and methods: Herein we report two cases of patients with a history of GIST in treatment with Imatinib. Results: After 4 weeks from treatment start, CT scan evaluation demonstrated a massive increase in the size of metastatic lesions, but a confirmatory PET excluded, in both patients, the presence of any metabolic activity in the previously known metastatic sites. Imatinib therapy was continued with subjective clinical benefit for 12 further months before a PET scan-confirmed disease progression had occurred in one patient and is still ongoing after 15 months in the other. Conclusion: These cases open the obvious question of whether conventional imaging techniques are adequate to assess the response to Imatinib treatment in GIST patients

A regional survey on Merkel cell carcinoma: a plea for uniform patient journey modeling and diagnostic–therapeutic pathway

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine cancer that usually affects the elderly and immunosuppressed in sun-exposed areas. Due to its rarity, it is frequently unrecognized, and its management is not standardized across medical centers, despite the more recent availability of immunotherapy, with avelumab as first-line treatment improving the prognosis even in advanced stages of disease. We conducted a purpose-designed survey of a selected sample of physicians working in the Lazio region, in Italy, to assess their awareness and knowledge of MCC as well as their perspective on assisted diagnostic and therapeutic pathways. The Lazio region, and in particular Rome, is one of the most important academic and non- academic center in Italy dedicated to the diagnosis and treatment of skin cancer. A total of 368 doctors (including 100 general practitioners, 72 oncologists, 87 dermatologists, 59 surgeons, and 50 anatomopathologists) agreed to be part of this survey. Surgeons, oncologists, and dermatologists thought themselves significantly more updated on MCC than primary care physicians, but more than half of the interviewees are interested in CCM training courses and training with clearer and more standardized care pathways. Significant differences have been reported from survey participants in terms of multidisciplinary team set up for MCC management. The identification of specialized centers and the improvement of communication pathways among different specialties, as well as between patients and physicians, could be very beneficial in improving patients’ journey modeling and starting a uniform diagnostic and therapeutic pathway for MCC patients in the new era of immunotherapies

CT radiomics-based machine learning classification of atypical cartilaginous tumours and appendicular chondrosarcomas

Background Clinical management ranges from surveillance or curettage to wide resection for atypical to higher-grade cartilaginous tumours, respectively. Our aim was to investigate the performance of computed tomography (CT) radiomics-based machine learning for classification of atypical cartilaginous tumours and higher-grade chondrosarcomas of long bones. Methods One-hundred-twenty patients with histology-proven lesions were retrospectively included. The training cohort consisted of 84 CT scans from centre 1 (n=55 G1 or atypical cartilaginous tumours; n=29 G2-G4 chondrosarcomas). The external test cohort consisted of the CT component of 36 positron emission tomography-CT scans from centre 2 (n=16 G1 or atypical cartilaginous tumours; n=20 G2-G4 chondrosarcomas). Bidimensional segmentation was performed on preoperative CT. Radiomic features were extracted. After dimensionality reduction and class balancing in centre 1, the performance of a machine-learning classifier (LogitBoost) was assessed on the training cohort using 10-fold cross-validation and on the external test cohort. In centre 2, its performance was compared with preoperative biopsy and an experienced radiologist using McNemar's test. Findings The classifier had 81% (AUC=0.89) and 75% (AUC=0.78) accuracy in identifying the lesions in the training and external test cohorts, respectively. Specifically, its accuracy in classifying atypical cartilaginous tumours and higher-grade chondrosarcomas was 84% and 78% in the training cohort, and 81% and 70% in the external test cohort, respectively. Preoperative biopsy had 64% (AUC=0.66) accuracy (p=0.29). The radiologist had 81% accuracy (p=0.75). Interpretation Machine learning showed good accuracy in classifying atypical and higher-grade cartilaginous tumours of long bones based on preoperative CT radiomic features

3D vs. 2D MRI radiomics in skeletal Ewing sarcoma: Feature reproducibility and preliminary machine learning analysis on neoadjuvant chemotherapy response prediction

ObjectiveThe extent of response to neoadjuvant chemotherapy predicts survival in Ewing sarcoma. This study focuses on MRI radiomics of skeletal Ewing sarcoma and aims to investigate feature reproducibility and machine learning prediction of response to neoadjuvant chemotherapy. Materials and methodsThis retrospective study included thirty patients with biopsy-proven skeletal Ewing sarcoma, who were treated with neoadjuvant chemotherapy before surgery at two tertiary sarcoma centres. 7 patients were poor responders and 23 were good responders based on pathological assessment of the surgical specimen. On pre-treatment T1-weighted and T2-weighted MRI, 2D and 3D tumour segmentations were manually performed. Features were extracted from original and wavelet-transformed images. Feature reproducibility was assessed through small geometrical transformations of the regions of interest mimicking multiple manual delineations, and intraclass correlation coefficient >0.75 defined feature reproducibility. Feature selection also consisted of collinearity and significance analysis. After class balancing in the training cohort, three machine learning classifiers were trained and tested on unseen data using hold-out cross-validation. Results1303 (77%) 3D and 620 (65%) 2D radiomic features were reproducible. 4 3D and 4 2D features passed feature selection. Logistic regression built upon 3D features achieved the best performance with 85% accuracy (AUC=0.9) in predicting response to neoadjuvant chemotherapy. ConclusionCompared to 2D approach, 3D MRI radiomics of Ewing sarcoma had superior reproducibility and higher accuracy in predicting response to neoadjuvant chemotherapy, particularly when using logistic regression classifier

SEMA6A/RhoA/YAP axis mediates tumor-stroma interactions and prevents response to dual BRAF/MEK inhibition in BRAF-mutant melanoma

Background: Despite the promise of dual BRAF/MEK inhibition as a therapy for BRAF-mutant (BRAF-mut) melanoma, heterogeneous responses have been observed in patients, thus predictors of benefit from therapy are needed. We have previously identified semaphorin 6A (SEMA6A) as a BRAF-mut-associated protein involved in actin cytoskeleton remodeling. The purpose of the present study is to dissect the role of SEMA6A in the biology of BRAF-mut melanoma, and to explore its predictive potential towards dual BRAF/MEK inhibition. Methods: SEMA6A expression was assessed by immunohistochemistry in melanoma cohort RECI1 (N = 112) and its prognostic potential was investigated in BRAF-mut melanoma patients from DFCI and TCGA datasets (N = 258). The molecular mechanisms regulated by SEMA6A to sustain tumor aggressiveness and targeted therapy resistance were investigated in vitro by using BRAF-mut and BRAF-wt melanoma cell lines, an inducible SEMA6A silencing cell model and a microenvironment-mimicking fibroblasts-coculturing model. Finally, SEMA6A prediction of benefit from dual BRAF/MEK inhibition was investigated in melanoma cohort RECI2 (N = 14). Results: Our results indicate higher protein expression of SEMA6A in BRAF-mut compared with BRAF-wt melanoma patients and show that SEMA6A is a prognostic indicator in BRAF-mut melanoma from TCGA and DFCI patients cohorts. In BRAF-mut melanoma cells, SEMA6A coordinates actin cytoskeleton remodeling by the RhoA-dependent activation of YAP and dual BRAF/MEK inhibition by dabrafenib+trametinib induces SEMA6A/RhoA/YAP axis. In microenvironment-mimicking co-culture condition, fibroblasts confer to melanoma cells a proliferative stimulus and protect them from targeted therapies, whereas SEMA6A depletion rescues the efficacy of dual BRAF/MEK inhibition. Finally, in BRAF-mut melanoma patients treated with dabrafenib+trametinib, high SEMA6A predicts shorter recurrence-free interval. Conclusions: Overall, our results indicate that SEMA6A contributes to microenvironment-coordinated evasion of melanoma cells from dual BRAF/MEK inhibition and it might be a good candidate predictor of short-term benefit from dual BRAF/MEK inhibition

PENGARUH HARGA DAN KUALITAS PELAYANAN TERHADAP KEPUASAN PELANGGAN SERTA DAMPAKNYA PADA LOYALITAS PELANGGAN GOJEK (Studi Pada Mahasiswa Kampus A Universitas Negeri Jakarta)

The purpose of this research are: 1) Knowing the influence of price to customer loyalty of bread product of Gojek brand in Kampus A UNJ. 2) To know the influence of service quality on customer loyalty of bread product of Gojek brand in Kampus A UNJ. The analysis done in this research is descriptive and explanatory analysis. The research was conducted with 200 customers of Gojek bread brand, while data collection technique was done by distributing questionnaires, which then processed using SPSS 21. The result of analysis showed that: 1) Price has a positive influence on consumer brand loyalty. bread products of Gojek brand. 2) Service quality has a positive influence on brand Loyalty of Gojek brand bakery products. All three variables have a positive relationship indicating the improvement of one other variable to be better too

Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial

No prospective data were available prior to 2021 to inform selection between combination BRAF and MEK inhibition versus dual blockade of programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) as first-line treatment options for BRAFV600-mutant melanoma. SECOMBIT (NCT02631447) was a randomized, three-arm, noncomparative phase II trial in which patients were randomized to one of two sequences with immunotherapy or targeted therapy first, with a third arm in which an 8-week induction course of targeted therapy followed by a planned switch to immunotherapy was the first treatment. BRAF/MEK inhibitors were encorafenib plus binimetinib and checkpoint inhibitors ipilimumab plus nivolumab. Primary outcome of overall survival was previously reported, demonstrating improved survival with immunotherapy administered until progression and followed by BRAF/MEK inhibition. Here we report 4-year survival outcomes, confirming long-term benefit with first-line immunotherapy. We also describe preliminary results of predefined biomarkers analyses that identify a trend toward improved 4-year overall survival and total progression-free survival in patients with loss-of-function mutations affecting JAK or low baseline levels of serum interferon gamma (IFNy). These long-term survival outcomes confirm immunotherapy as the preferred first-line treatment approach for most patients with BRAFV600-mutant metastatic melanoma, and the biomarker analyses are hypothesis-generating for future investigations of predictors of durable benefit with dual checkpoint blockade and targeted therapy

Quality of life and emotional distress in sarcoma patients diagnosed during COVID-19 pandemic: a supplementary analysis from the SarCorD study

BackgroundThe COVID-19 outbreak had a negative psychological impact on cancer patients. In this study, we analyzed emotional distress and quality of life in patients diagnosed with sarcoma during the first year of the pandemic compared to the previous year.MethodsWe retrospectively enrolled patients with soft tissue, bone sarcoma, and aggressive benign musculoskeletal diseases diagnosed during the pandemic (COVID group) or the year before (control group) at the IRCCS Regina Elena National Cancer Institute in Rome. Patients who had undergone a psychological assessment with the EORTC QLQ-C30 and the Distress Thermometer at diagnosis were included in the final analysis. We analyzed whether there is a difference in the various domains of quality of life between the two groups and whether there are changes over time in each group.ResultsWe enrolled 114 patients (72 control group; 42 COVID group), affected by soft tissue (64%), bone sarcoma (29%), and aggressive benign musculoskeletal diseases (7%). We did not observe significant differences in the health-related quality of life domains in the control and COVID groups, except for the financial domain (p = 0.039), with 9.7% vs. 23.8% of patients with a score > 0 in the control and COVID groups, respectively. We observed emotional distress at diagnosis in 48.6% of patients in the control group vs. 69.0% in the COVID group (p = 0.034). In the control group, we observed an improvement in physical function (p = 0.043) and in QoL (p = 0.022), while in the COVID group, we observed a deterioration in role function (p = 0.044) during follow-up. In the COVID group, 22.2% of patients were concerned about COVID-19, 61.1% by tumor, 91.1% stated that the pandemic worsened their subjective perception of cancer, and 19.4% perceived that their quality of care had worsened.ConclusionWe observed a higher level of distress among patients diagnosed during the pandemic compared to the year before, probably due to the increased concern for both infection and cancer, the worsened perception of health status, and the perception of a poorer quality of health care