Abhishek Bhattacharya

Background: Tumor invasion and malignant transformation are spatiotemporally coordinated processes that shape clinical behavior, diagnostic classification, and treatment response. Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive tumors that can arise sporadically or in people with neurofibromatosis type 1 (NF-1), yet how distinct spatial niches underlie MPNST intratumor heterogeneity, local invasion, or malignant transformation from benign precursors is not fully understood. Methods: We integrate spatial analysis of 50,896 transcriptomes from 15 human MPNSTs with deep learning image analysis to define the interplay between genetic alterations, the immune microenvironment, and epigenetic cell fate regulation in MPNST invasion and transformation. Results: Spatial transcriptomics reveal distinct infiltrating immune cells and immunomodulatory spatial clusters in sporadic compared to NF-1–associated MPNSTs. Local invasion is marked by spatially defined immunomodulatory and dedifferentiation programs. Analysis of 2 NF-1–associated MPNSTs with contiguous morphologically defined neurofibroma and MPNST components demonstrates that NF-1–associated tumors exhibit a similar malignant transformation process associated with dynamic immune infiltration, chromosome 9p loss, and dedifferentiation concomitant with increased cell proliferation. Finally, deep learning morphology encoders were trained on spatial transcriptomic data to predict spatial transcriptomic cluster identity and chromosome 9p loss from hematoxylin and eosin–stained images although the generalizability of such encoders remains a challenge. Conclusions: Our data provide a spatial framework for peripheral nerve sheath tumor transformation although the limited sample size of the present cohort will require additional validation of the proposed model.

Smoking cessation following a cancer diagnosis is associated with improved outcomes, including reduced overall mortality. We searched the websites of 64 NCI-designated cancer centers that provide clinical cancer care to adults for webpages about smoking cessation and assessed the quality of the available content. Thirty-five of 64 (55%) websites hosted smoking cessation–focused webpages. Of those 35 webpages, 20 (57%) explicitly stated that smoking cessation decreases overall mortality, 8 (23%) included information about smoking cessation medications, 9 (26%) offered behavioral counseling tips such as setting a quit date or advising on habit replacement, and 11 (31%) described the risks and benefits of e-cigarette use. Links to other established smoking cessation organizations were evaluated; 15 (43%) webpages linked to smokefree.gov, 20 (57%) listed the phone numbers for state or national quitlines, and 5 (14%) described the Cancer Center Cessation Initiative. The average estimated reading level of the webpages was 10.5. These findings suggest that cancer center websites, which patients may access for trustworthy online medical information, often lack actionable and/or comprehensible information to help patients with cancer quit smoking. There is an opportunity to strengthen online communication to patients about effective smoking cessation strategies, which may help patients live longer and healthier lives.Prevention Relevance:Smoking cessation is paramount to preventing the onset of cancer, and in those who have a cancer diagnosis, quitting smoking will improve outcomes and also help reduce the risk of developing a second cancer.

Supplementary Material 1: Links to websites used for data collection

Smoking cessation following a cancer diagnosis is associated with improved outcomes, including reduced overall mortality. We searched the websites of 64 NCI-designated cancer centers that provide clinical cancer care to adults for webpages about smoking cessation and assessed the quality of the available content. Thirty-five of 64 (55%) websites hosted smoking cessation–focused webpages. Of those 35 webpages, 20 (57%) explicitly stated that smoking cessation decreases overall mortality, 8 (23%) included information about smoking cessation medications, 9 (26%) offered behavioral counseling tips such as setting a quit date or advising on habit replacement, and 11 (31%) described the risks and benefits of e-cigarette use. Links to other established smoking cessation organizations were evaluated; 15 (43%) webpages linked to smokefree.gov, 20 (57%) listed the phone numbers for state or national quitlines, and 5 (14%) described the Cancer Center Cessation Initiative. The average estimated reading level of the webpages was 10.5. These findings suggest that cancer center websites, which patients may access for trustworthy online medical information, often lack actionable and/or comprehensible information to help patients with cancer quit smoking. There is an opportunity to strengthen online communication to patients about effective smoking cessation strategies, which may help patients live longer and healthier lives. Prevention Relevance: Smoking cessation is paramount to preventing the onset of cancer, and in those who have a cancer diagnosis, quitting smoking will improve outcomes and also help reduce the risk of developing a second cancer.

Melanoma will affect an estimated 73,000 new cases this year and result in 9,000 deaths, yet precise diagnosis remains a serious problem. Without early detection and preventative care, melanoma can quickly spread to become fatal (Stage IV 5-year survival rate is 20-10%) from a once localized skin lesion (Stage IA 5- year survival rate is 97%). There is no biomarker for melanoma in clinical use, and the current diagnostic criteria for skin lesions remains subjective and imprecise. Accurate diagnosis of melanoma relies on a histopathologic gold standard; thus, aggressive excision of melanocytic skin lesions has been the mainstay of treatment. It is estimated that 36 biopsies are performed for every melanoma confirmed by pathology among excised lesions. There is significant morbidity in misdiagnosing melanoma such as progression of the disease for a false negative prediction vs the risks of unnecessary surgery for a false positive prediction. Every year, poor diagnostic precision adds an estimated $673 million in overall cost to manage the disease.