Body mass index and adiposity influence responses to immune checkpoint inhibition in endometrial cancer.

BACKGROUND: Obesity is the foremost risk factor in the development of endometrial cancer (EC). However, the impact of obesity on the response to immune checkpoint inhibitors (ICI) in EC remains poorly understood. This retrospective study investigates the association between body mass index (BMI), body fat distribution, and clinical and molecular characteristics of EC patients treated with ICI. METHODS: We analyzed progression-free survival (PFS) and overall survival (OS) in EC patients treated with ICI, categorized by BMI, fat mass distribution, and molecular subtypes. Incidence of immune-related adverse events (irAE) after ICI was also assessed based on BMI status. RESULTS: 524 EC patients were included in the study. Overweight and obese patients exhibited a significantly prolonged PFS and OS compared to normal BMI patients after treatment with ICI. Multivariable Cox regression analysis confirmed the independent association of overweight and obesity with improved PFS and OS. Elevated visceral adipose tissue (VAT) was identified as a strong independent predictor for improved PFS to ICI. Associations between obesity and OS/PFS were particularly significant in the copy number-high/TP53abnormal (CN-H/TP53abn) EC molecular subtype. Finally, obese patients demonstrated a higher irAE rate compared to normal BMI individuals. CONCLUSION: Obesity is associated with improved outcomes to ICI in EC patients and a higher rate of irAEs. This association is more pronounced in the CN-H/TP53abn EC molecular subtype. FUNDING: NIH/NCI Cancer Center Support Grant P30CA008748 (MSK). K08CA266740 and MSK Gerstner Physician Scholars Program (J.C.O). RUCCTS Grant #UL1 TR001866 (N.G-B and C.S.J). Cycle for survival and Breast Cancer Research Foundation grants (B.W).

Clinical utility of radiomics at baseline rectal MRI to predict complete response of rectal cancer after chemoradiation therapy.

PURPOSE: To investigate the value of T2-radiomics combined with anatomical MRI staging criteria from pre-treatment rectal MRI in predicting complete response to neoadjuvant chemoradiation therapy (CRT). METHODS: This retrospective study included patients with locally advanced rectal cancer who underwent rectal MRI before neoadjuvant CRT from October 2011 to January 2015 and then surgery. Surgical histopathologic analysis was used as the reference standard for pathologic complete response. Anatomical MRI staging criteria were extracted from our institutional standardized radiology report. In radiomics analysis, one radiologist manually segmented the primary tumor on T2-weighted images for all 102 patients (i.e., training set); two different radiologists independently segmented 66/102 patients (i.e., validation set). 108 radiomics features were extracted. Then, scanner-independent features were identified and least absolute shrinkage operator analysis was used to extract a radiomics score. Finally, a support vector machine model combining the radiomics score and anatomical MRI staging criteria was compared against both anatomical MRI-only and radiomics-only models using the deLong test. RESULTS: The study included 102 patients (42 women; median age = 61 years).The radiomics score produced an area under the curve (AUC) of 0.75. Comparable results were found using the validation set (AUCs = 0.75 and 0.71 for each radiologist, respectively). The anatomical MRI-only model had an accuracy of 67% (sensitivity 42%, specificity 72%); when adding the radiomics score, the accuracy increased to 74% (sensitivity 58%, specificity 77%). CONCLUSION: Combining T2-radiomics and anatomical MRI staging criteria from pre-treatment rectal MRI may help to stratify patients based on the prediction of treatment response to neoadjuvant therapy.

A rectal cancer organoid platform to study individual responses to chemoradiation.

Rectal cancer (RC) is a challenging disease to treat that requires chemotherapy, radiation and surgery to optimize outcomes for individual patients. No accurate model of RC exists to answer fundamental research questions relevant to patients. We established a biorepository of 65 patient-derived RC organoid cultures (tumoroids) from patients with primary, metastatic or recurrent disease. RC tumoroids retained molecular features of the tumors from which they were derived, and their ex vivo responses to clinically relevant chemotherapy and radiation treatment correlated with the clinical responses noted in individual patients' tumors. Upon engraftment into murine rectal mucosa, human RC tumoroids gave rise to invasive RC followed by metastasis to lung and liver. Importantly, engrafted tumors displayed the heterogenous sensitivity to chemotherapy observed clinically. Thus, the biology and drug sensitivity of RC clinical isolates can be efficiently interrogated using an organoid-based, ex vivo platform coupled with in vivo endoluminal propagation in animals.

Osteoid osteoma of the spine: CT-guided monopolar radiofrequency ablation.

CT-guided percutaneous radiofrequency ablation and laser photocoagulation have become the methods of choice for the treatment of all osteoid osteomas except those in contact with neural structures. We report 10 patients with spinal osteoid osteoma adjacent to the neural elements treated with 12 sessions of CT-guided monopolar radiofrequency ablation. The size range of the lesion was 3-14 mm (mean, 7.5 mm) and the distance between the nidus and the adjacent spinal cord or nerve root was 2-12 mm (mean, 5 mm). No intact cortex between the tumor and the spinal cord or nerve roots constituted an exclusion criterion because of a higher risk of undesirable neurotoxic effects. Patients were under general anesthesia. After location of the lesion, a 11G-bone biopsy was introduced into the nidus. The radiofrequency electrode was inserted through the biopsy needle and heated at 90 degrees C for 4 min. Primary success was obtained in eight patients. At follow-up (mean, 19.5 months; range, 6-24 months), pain persisted in two patients after 2 months. Both of them were re-treated. All patients are currently pain-free and complications were not detected. In our opinion, radiofrequency ablation can also be considered the treatment of choice for spinal osteoid osteoma.

Pathologic fractures in children.

Fractures through bone tumors are often difficult to treat. We reviewed our combined experience with this problem in children, as well as the existing literature, to formulate management guidelines. For this study, prospective databases (1987 to 2002) from three referral centers were screened for pathologic fractures occurring under the age of 14 years. One hundred five patients presented with fracture through unicameral bone cyst, nonossifying fibroma, fibrous dysplasia, aneurysmal bone cyst and osteosarcoma. Seventeen patients were excluded. The most common primary locations were the proximal humerus and proximal femur. Pathologic fracture through nonossifying fibroma had the best outcome; union occurred with nonsurgical treatment in all cases. Unicameral bone cyst required surgical treatment to avoid persistence of the cyst and refracture. However fracture healing was predictable without surgical treatment. Proximal femoral lesions tended to heal in malunion if not fixed surgically. Aneurysmal bone cyst required surgical treatment for the lesion to heal and to allow the fracture to heal as well. Percutaneous sclerotherapy may be the treatment of choice for many of these lesions. Fibrous dysplasia allows fracture healing with nonoperative therapy. Progressive deformity requires followup and surgical correction. Malignant lesions presenting a pathologic fracture are best managed by initial nonoperative therapy during investigation and neoadjuvant therapy when possible, followed by definitive treatment.