Southwest Oncology Group S0826: A phase 2 trial of SCH 727965 (NSC 727135, dinaciclib) in patients with stage IV melanoma.

BACKGROUND: Cell cycle inhibition is an established therapeutic approach for some cancers. A multicenter, single-arm, phase 2 trial (ClinicalTrials.gov identifier NCT00937937) of the cyclin-dependent kinase inhibitor SCH 727965 (NSC 747135; dinaciclib) was conducted in patients with metastatic melanoma to determine its clinical activity. METHODS: Patients with metastatic melanoma of cutaneous or mucosal origin were eligible if they had zero to one previous treatments, a Zubrod performance status of 0-1, and adequate organ function. SCH 727965 50 mg/m2 was given intravenously every 3 weeks until progression. Co-primary end points were 1-year overall survival (OS) and 6-month progression-free survival (PFS). RESULTS: Seventy-two patients were enrolled from July 1, 2009, to November 1, 2010, at 24 institutions. Sixty-eight percent of patients had M1c disease, and 43% had elevated lactate dehydrogenase levels. Twenty-eight patients (39%) experienced grade 4 adverse events, including 20 cases of neutropenia. Sixty-seven patients were evaluable for response. There was a response in zero of 67 patients (95% confidence interval [CI], 0%-5%), and stable disease was observed in 21%. The estimated median PFS was 1.4 months (95% CI, 1.4-1.5 months), and the 6-month PFS rate was 6% (2%-13%). The median OS was 8.2 months (95% CI, 5.5-10.5 months), and the 1-year OS rate was 38% (95% CI, 26%-49%). CONCLUSIONS: This multicenter, US National Cancer Institute Cancer Therapy Evaluation Program-sponsored trial of SCH 727965 was conducted at a time when the current generation of effective therapies for melanoma were not available. Although the null hypothesis of 1-year OS was rejected, the minimal PFS impact and substantive toxicity indicated that this regimen lacks justification for further investigation as a single agent.

Upregulation of proto-oncogene ski by thyroid hormone in the intestine and tail during Xenopus metamorphosis.

Thyroid hormone (T3) is important for adult organ function and vertebrate development, particularly during the postembryonic period when many organs develop/mature into their adult forms. Amphibian metamorphosis is totally dependent on T3 and can be easily manipulated, thus offering a unique opportunity for studying how T3 controls postembryonic development in vertebrates. Numerous early studies have demonstrated that T3 affects frog metamorphosis through T3 receptor (TR)-mediated regulation of T3 response genes, where TR forms a heterodimer with RXR (9-cis retinoic acid receptor) and binds to T3 response elements (TREs) in T3 response genes to regulate their expression. We have previously identified many candidate direct T3 response genes in Xenopus tropicalis tadpole intestine. Among them is the proto-oncogene Ski, which encodes a nuclear protein with complex function in regulating cell fate. We show here that Ski is upregulated in the intestine and tail of premetamorphic tadpoles upon T3 treatment and its expression peaks at stage 62, the climax of metamorphosis. We have further discovered a putative TRE in the first exon that can bind to TR/RXR in vitro and mediate T3 regulation of the promoter in vivo. These data demonstrate that Ski is activated by T3 through TR binding to a TRE in the first exon during Xenopus tropicalis metamorphosis, implicating a role of Ski in regulating cell fate during metamorphosis.

Targeted Therapy and Traditional Chemotherapy in Melanoma and Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (cSCC) and melanoma encompass the majority of all malignant skin cancers. There has been an increase in their incidence globally in recent decades. In cases of high-risk, unresectable, or metastatic disease; or when patient factors or preferences limit the availability of conventional surgery or radiotherapy; or a systemic therapy is often warranted. Our improved understanding of the molecular and immune pathogenesis underlying tumor growth and development has been critical in advancing cancer therapeutics. Over the past several years, several new systemic agents have been approved for both diseases. The role of cytotoxic chemotherapy is gradually waning with the introduction of targeted therapy and immunotherapy. In this article, we review the current and relevant literature and evidence of cytotoxic chemotherapy, targeted therapy, and immune checkpoint inhibitors in the adjuvant and neoadjuvant settings for cSCC and melanoma. Additionally, we describe their role in the unresectable or metastatic disease setting.

Trousseau's Syndrome in Cholangiocarcinoma: The Risk of Making the Diagnosis.

We report a case of Trousseau's syndrome with cholangiocarcinoma complicated by a fatal pulmonary embolism after liver biopsy. A 69-year-old man who presented with right upper quadrant pain was found to have portal vein thrombosis and nonspecific liver hypodensities after imaging by computerized tomography. Following four days of anticoagulation, heparin was held for percutaneous liver biopsy. After the biopsy, he developed acute hepatic failure, acute kidney injury, lactic acidemia, and expired. Autopsy revealed intrahepatic cholangiocarcinoma and a pulmonary embolism. Trousseau's syndrome with cholangiocarcinoma is rarely reported and has a poor prognosis. This case highlights a fundamental challenge in the diagnosis and early management of intrahepatic cholangiocarcinoma with hypercoagulability. Diagnostic biopsy creates an imperative to reduce post-operative bleeding risk, but this conflicts with the need to reduce thrombotic risk in a hypercoagulable state. Considering the risk of withholding anticoagulation in patients with proven or suspected cholangiocarcinoma complicated by portal vein thrombosis, physicians should consider biopsy procedures with lesser bleeding risks, such as transjugular liver biopsy or plugged percutaneous liver biopsy, to minimize interruption of anticoagulation.

Characterization of Arabidopsis NEET reveals an ancient role for NEET proteins in iron metabolism.

The NEET family is a newly discovered group of proteins involved in a diverse array of biological processes, including autophagy, apoptosis, aging, diabetes, and reactive oxygen homeostasis. They form a novel structure, the NEET fold, in which two protomers intertwine to form a two-domain motif, a cap, and a unique redox-active labile 2Fe-2S cluster binding domain. To accelerate the functional study of NEET proteins, as well as to examine whether they have an evolutionarily conserved role, we identified and characterized a plant NEET protein. Here, we show that the Arabidopsis thaliana At5g51720 protein (At-NEET) displays biochemical, structural, and biophysical characteristics of a NEET protein. Phenotypic characterization of At-NEET revealed a key role for this protein in plant development, senescence, reactive oxygen homeostasis, and Fe metabolism. A role in Fe metabolism was further supported by biochemical and cell biology studies of At-NEET in plant and mammalian cells, as well as mutational analysis of its cluster binding domain. Our findings support the hypothesis that NEET proteins have an ancient role in cells associated with Fe metabolism.

Incidence, prevalence, costs, and impact on disability of common conditions requiring rehabilitation in the United States: stroke, spinal cord injury, traumatic brain injury, multiple sclerosis, osteoarthritis, rheumatoid arthritis, limb loss, and back pain.

OBJECTIVE: To determine the relative incidence, prevalence, costs, and impact on disability of 8 common conditions treated by rehabilitation professionals. DATA SOURCES: Comprehensive bibliographic searches using MEDLINE, Google Scholar, and UpToDate, (June, 2013). DATA EXTRACTION: Two review authors independently screened the search results and performed data extraction. Eighty-two articles were identified that had relevant data on the following conditions: Stroke, Spinal Cord Injury, Traumatic Brain Injury, Multiple Sclerosis, Osteoarthritis, Rheumatoid Arthritis, Limb Loss, and Back Pain. DATA SYNTHESIS: Back pain and arthritis (osteoarthritis, rheumatoid arthritis) are the most common and costly conditions we analyzed, affecting more than 100 million individuals and costing greater than $200 billion per year. Traumatic brain injury, while less common than arthritis and back pain, carries enormous per capita direct and indirect costs, mostly because of the young age of those involved and the severe disability that it may cause. Finally, stroke, which is often listed as the most common cause of disability, is likely second to both arthritis and back pain in its impact on functional limitations. CONCLUSIONS: Of the common rehabilitation diagnoses we studied, musculoskeletal conditions such as back pain and arthritis likely have the most impact on the health care system because of their high prevalence and impact on disability.

Rapid Life-Saving Response to Anti-PD-1 in a Solid Organ Transplant Recipient With Metastatic Cutaneous Squamous Cell Carcinoma: A Case Report and Review.

SUMMARY: Anti-programmed cell death protein 1 (PD-1) therapy is considered effective in the treatment of metastatic or locally advanced cutaneous squamous cell carcinoma but the use of these agents in solid organ transplant recipients (SOTRs) is often taken with caution. While anti-tumor effects without graft rejection have been reported, studies have shown high rates of fatal graft rejection with immune checkpoint therapy. In this case report, we present an SOTR patient with life-threatening, acute hypoxic respiratory failure due to rapidly progressive metastatic cutaneous squamous cell carcinoma with lung and pleural involvement. Modification of their immunosuppressive regimen and treatment with front-line anti-PD-1 inhibitor, pembrolizumab, led to rapid clinical response with near complete resolution of metastatic pulmonary disease and no long-term evidence of graft rejection. Our case report shows that front-line treatment with PD-1 inhibitors can be safely administered in SOTR patients with rapid metastatic disease control.

Review of recent advances in managing periocular skin malignancies.

Management of cutaneous malignancies can be particularly challenging when they are located in the periocular region. The standard of care for localized disease is complete surgical excision, but this may not be possible without significant disruption to visual structures and facial appearance. Definitive radiation may be an option for some patients who cannot or do not wish to undergo surgery. Advances in systemic treatment options for locally advanced and metastatic skin cancers in the past 10 years have prompted investigation into neoadjuvant treatment of periocular cancers. The use of chemotherapy, immune checkpoint inhibitors, and targeted therapies have all been reported with varying degrees of success. For many patients, targeted therapies or immune checkpoint inhibitors should be considered depending on the cancer type, symptoms, and goals with the input of a multidisciplinary cancer care team. In this article, we systematically review the latest updates in surgical, radiotherapeutic, and medical management of periocular malignancies.

Successful Treatment of Metastatic Primary Cutaneous Adnexal Carcinoma With a PD-1 Inhibitor.

SUMMARY: Standard of care treatment for metastatic cutaneous adnexal carcinomas is not well established. In this case report, we highlight the successful use of anti-programmed cell death protein 1 (anti-PD-1) therapy in treating a patient with low tumor mutation burden, microsatellite stable, high programmed death-ligand 1 (PD-L1) gene expression, metastatic primary cutaneous adnexal carcinoma with significant radiographic, and circulating tumor DNA response with durable benefit. Immune checkpoint inhibitors hold promise as a future treatment option in rare instances of metastatic disease from primary skin adnexal carcinoma. Further studies are needed to identify better immune checkpoint inhibitor predictive biomarkers for rare, advanced-stage non-melanoma skin cancers.

Using single antigen specificity magnetic beads for the isolation of specific antibodies against HLA antigens.

The presence of multiple donor-specific antibodies (DSAs) targeting HLA antigens poses a challenge to transplantation. Various techniques, including the use of recombinant cell lines and crossmatch cells have been developed to isolate DSAs. To simplify the extraction of HLA-specific DSAs from complex sera, we introduced magnetic beads with single HLA specificity (MagSort). Sera were treated with MagSort, allowing HLA-specific antibodies to bind to the beads, and these specific antibodies were subsequently eluted. MagSort beads, coated with 59 different HLA variants, underwent testing through 1329 adsorption/elution processes, demonstrating their effectiveness and specificity in adsorbing and eluting HLA-specific antibodies. The MagSort method proves comparable to the cell method, showing similar isolated antibody binding patterns. The isolated antibody binding patterns from MagSort reveal both known eplets and unknown patterns, suggesting its utility for eplet discovery. Additionally, MagSort proved effective in extracting signals for flow cytometry cross-matching, offering a means to assess the binding capability of isolated antibodies against specific donor cells.

Clinical cell-surface targets in metastatic and primary solid cancers.

Therapies against cell-surface targets (CSTs) represent an emerging treatment class in solid malignancies. However, high-throughput investigations of CST expression across cancer types have been reliant on data sets of mostly primary tumors, despite therapeutic use most commonly in metastatic disease. We identified a total of 818 clinical trials of CST therapies with 78 CSTs. We assembled a data set spanning RNA-seq and microarrays in 7,927 benign samples, 16,866 primary tumor samples, and 6,124 metastatic tumor samples. We also utilized single-cell RNA-seq data from 36 benign tissues and 558 primary and metastatic tumor samples, and matched RNA versus protein expression in 29 benign tissue samples, 1,075 tumor samples, and 942 cell lines. High RNA expression accurately predicted high protein expression across CST therapies in benign tissues, tumor samples, and cell lines. We compared metastatic versus primary tumor expression, identified potential opportunities for repositioning, and matched cell lines to tumor types based on CST and global RNA expression. We evaluated single-cell heterogeneity across tumors, and identified rare normal cell subpopulations that may contribute to toxicity. Finally, we identified combinations of CST therapies for which bispecific approaches could improve tumor specificity. This study helps better define the landscape of CST expression in metastatic and primary cancers.

Linking genes of unknown function with abiotic stress responses by high-throughput phenotype screening.

Over 13% of all genes in the Arabidopsis thaliana genome encode for proteins classified as having a completely unknown function, with the function of >30% of the Arabidopsis proteome poorly characterized. Although empirical data in the form of mRNA and proteome profiling experiments suggest that many of these proteins play an important role in different biological processes, their functional characterization remains one of the major challenges in modern biology. To expand the annotation of genes with unknown function involved in the response of Arabidopsis to different environmental stress conditions, we selected 1007 such genes and tested the response of their corresponding homozygous T-DNA insertional mutants to salinity, oxidative, osmotic, heat, cold and hypoxia stresses. Depending on the specific abiotic stresses tested, 12-31% of mutants had an altered stress-response phenotype. Interestingly, 832 out of 1007 mutants showed tolerance or sensitivity to more than one abiotic stress treatment, suggesting that genes of unknown function could play an important role in abiotic stress-response signaling, or general acclimation mechanisms. Further analysis of multiple stress-response phenotypes within different populations of mutants revealed interesting links between acclimation to heat, cold and oxidative stresses, as well as between sensitivity to ABA, osmotic, salinity, oxidative and hypoxia stresses. Our findings provide a significant contribution to the biological characterization of genes with unknown function in Arabidopsis and demonstrate that many of these genes play a key role in the response of plants to abiotic stresses.

The impact of type 2 diabetes on numeric pain score reduction following cervical transforaminal epidural steroid injections.

OBJECTIVE: This study aimed to determine whether the presence of type 2 diabetes impairs the therapeutic response to transforaminal cervical epidural steroid injections (TF-CESI) in the treatment of pain due to cervical radiculopathy. DESIGN: This is a retrospective cohort study of patients with cervical radiculopathy who underwent TF-CESI performed by a single physician. SETTING: Single community-based multidisciplinary pain clinic and ambulatory surgery center. INTERVENTIONS: Patients underwent from one to three TF-CESI with dexamethasone or triamcinolone. MAIN OUTCOME MEASURES: Change in self-reported numerical pain score. RESULTS: Out of 387 charts reviewed, complete data were available for 329 subjects who underwent TF-CESI from February 2006 through January 2010. The injections consisted of either 40 mg triamcinolone or 15 mg dexamethasone. Of the 329 total subjects, 35 had type 2 diabetes and 294 did not. The diabetic group had a mean age of 58.1 years with standard deviation (SD) of 11.2, mean body mass index (BMI) of 33.1 (SD 7.1), mean pre-procedure pain score of 6.7 (SD 2.2) and mean reduction in pain score of 2.5 (SD 2.4). The non-diabetic group had a mean age of 52.8 (SD 12.4), mean BMI of 28.2 (SD 5.4), mean pre-procedure pain score of 6.7 (SD 1.8), and mean reduction in pain score of 2.4 (SD 2.2). A two-sample t test with equivalent variance showed no statistically significant difference in the mean reduction in pain score between the diabetic and non-diabetic groups. The patients in the diabetic group were typically older and had higher BMIs. CONCLUSIONS: The efficacy of TF-CESI for treating cervical radicular pain in this set of 329 patients was independent of the presence of type 2 diabetes.

Evaluation of the Prognostic Role of Liver Metastases on Patient Outcomes: Systematic Review and Meta-analysis.

ABSTRACT: The liver is a common site of metastasis for many primary malignancies, but the quantitative impact on survival is unknown. We performed a systematic review and meta-analysis of 83 studies (604,853 patients) assessing the overall hazard associated with liver metastases by primary tumor type and treatment regimen. The pooled overall survival hazard ratio (HR) for all included studies was 1.77 (95% confidence interval [CI], 1.62-1.93). Patients with breast cancer primaries fared the worst (HR, 2.37; 95% CI, 1.64-3.44), as did patients treated with immunotherapies (HR, 1.86; 95% CI, 1.42-2.42). Liver metastases negatively impact survival, necessitating new approaches to disease management.

Clinical EEG slowing induced by electroconvulsive therapy is better described by increased frontal aperiodic activity.

Electroconvulsive therapy (ECT) is one of the most efficacious interventions for treatment-resistant depression. Despite its efficacy, ECT's neural mechanism of action remains unknown. Although ECT has been associated with "slowing" in the electroencephalogram (EEG), how this change relates to clinical improvement is unresolved. Until now, increases in slow-frequency power have been assumed to indicate increases in slow oscillations, without considering the contribution of aperiodic activity, a process with a different physiological mechanism. In this exploratory study of nine MDD patients, we show that aperiodic activity, indexed by the aperiodic exponent, increases with ECT treatment. This increase better explains EEG "slowing" when compared to power in oscillatory peaks in the delta (1-3 Hz) range and is correlated to clinical improvement. In accordance with computational models of excitation-inhibition balance, these increases in aperiodic exponent are linked to increasing levels of inhibitory activity, suggesting that ECT might ameliorate depressive symptoms by restoring healthy levels of inhibition in frontal cortices.

Neutrophil-to-eosinophil ratio as a biomarker for clinical outcomes in advanced stage melanoma patients treated with anti-PD-1 therapy.

Neutrophil-to-lymphocyte ratios (NLR) and eosinophil counts are associated with improved survival in melanoma patients treated with immune checkpoint inhibitors, but no study has investigated neutrophil-to-eosinophil ratios (NER) as a predictive indicator in this population. In this retrospective study evaluating anti-PD-1 treated patients with advanced melanoma, progression-free survival (PFS), overall survival (OS), objective response rates (ORR), and risk of high-grade (grade ≥3) immune-related adverse events (irAEs) were compared between groups defined by median pretreatment NLR and NER as well as median NLR and NER at 1-month post-treatment. Lower baseline NLR and NER were associated with improved OS [HR: 0.504, 95% CI: 0.328-0.773, p = .002 and HR: 0.442, 95% CI: 0.288-0.681, p < .001, respectively] on univariate testing. After accounting for multiple covariates, our multivariate analysis found that lower pretreatment NER was associated with better ORR (by irRECIST) (OR: 2.199, 95% CI: 1.071-4.582, p = .033) and improved OS (HR: 0.480, 95% CI: 0.296-0.777, p = .003). Baseline NLR, 1-month NLR, and 1-month NER were not associated with ORR, PFS, or OS outcomes; but 1-month NER correlated with lower risk of grade ≥3 irAEs (OR: 0.392, 95% CI: 0.165-0.895, p = .029). Our findings suggest baseline NER merits additional investigation as a novel prognostic marker for advanced melanoma patients receiving anti-PD-1-based regimens.

Successful use of secukinumab in two melanoma patients with immune checkpoint inhibitor-induced inflammatory arthropathy.

Immune-related adverse events (irAEs) are a major concern when treating cancer patients with immune checkpoint inhibitor (ICI) therapy. Selecting the most appropriate management of irAEs remains an ongoing challenge because prolonged use of glucocorticoids come with their own side effects and may counteract the antineoplastic effects from immunotherapy. In this case report, we present two patients with metastatic melanoma who developed symptoms of inflammatory arthritis attributed to ICI therapy. We found that treatment with secukinumab, an anti-IL-17A inhibitor, effectively managed their symptoms and did not lead to tumor progression. Our study suggests that secukinumab can be a safe and effective treatment option for ICI-induced inflammatory arthropathy.

Immune-related adverse events (irAEs) are unwanted side effects commonly seen in cancer patients treated with immunotherapy. A frequently underreported irAE is inflammation of the joints (ankles, knees, shoulders, etc.), which is known as inflammatory arthropathy. Inflammatory arthropathy is frequently treated with steroids, but there is concern that it may counteract the anticancer effect from immunotherapy. Alternative treatments are needed to better treat this irAE without compromising the benefit of immunotherapy. In this case report, we present two patients with stage 4 melanoma who developed immunotherapy-induced inflammatory arthropathy and were successfully treated with secukinumab. We found that treating the inflammatory arthropathy was safe, effective, and did not lead to cancer progression in either patient.

Early Response Assessment in Advanced Stage Melanoma Treated with Combination Ipilimumab/Nivolumab.

Background: Standard combination ipilimumab/nivolumab (I/N) is given as 4 induction doses for advanced stage melanoma followed by nivolumab single-agent maintenance therapy. While many patients receive less than 4 doses due to immune-related toxicities, it is unclear if fewer doses of I/N may still provide long term clinical benefit. Our aim is to determine if response assessment after 1 or 2 doses of I/N can predict long-term survival and assess if fewer doses of I/N can lead to similar survival outcomes. Methods: We performed a retrospective analysis on a cohort of patients with advanced melanoma who w0ere treated with standard I/N. Cox regression of progression-free survival (PFS) and overall survival (OS) models were performed to assess the relationship between response after 1 or 2 doses of I/N and risk of progression and/or death. Clinical benefit response (CBR) was assessed, defined as SD (stable disease) + PR (partial response) + CR (complete response) by imaging. Among patients who achieved a CBR after 1 or 2 doses of I/N, a multivariable Cox regression of survival was used to compare 1 or 2 vs 3 or 4 doses of I/N adjusted by known prognostic variables in advanced melanoma. Results: 199 patients were evaluated. Patients with CBR after 1 dose of I/N had improved PFS (HR: 0.16, 95% CI 0.08-0.33; p<0.001) and OS (HR: 0.12, 0.05-0.32; p<0.001) compared to progressive disease (PD). Patients with CBR (vs PD) after 2 doses of I/N also had improved PFS (HR: 0.09, 0.05-0.16; p<0.001) and OS (HR: 0.07, 0.03-0.14; p<0.001). There was no survival risk difference comparing 1 or 2 vs 3 or 4 doses of I/N for PFS (HR: 0.95, 0.37-2.48; p=0.921) and OS (HR: 1.04, 0.22-4.78; p=0.965). Conclusions: Early interval imaging with response during induction with I/N may be predictive of long-term survival in advanced stage melanoma. CBR after 1 or 2 doses of I/N is associated with favorable survival outcomes, even in the setting of fewer I/N doses received. Further studies are warranted to evaluate if electively administering fewer combination I/N doses despite tolerance in select patients may balance the benefits of therapy while decreasing toxicities.

Viral Status Predicts the Patterns of Genome Methylation and Decitabine Response in Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma that is classified as Merkel cell polyomavirus-positive (virus positive [VP]) or Merkel cell polyomavirus-negative (virus negative [VN]). Epigenetic changes, such as DNA methylation, can alter gene expression and influence cancer progression. However, patterns of DNA methylation and the therapeutic efficacy of hypomethylating agents have not been fully explored in MCC. We characterized genome-wide DNA methylation in 16 MCC cell lines from both molecular subclasses in comparison with other cancer types and found that the overall profile of MCC is similar to that of small-cell lung carcinoma. Comparison of VP MCC with VN MCC revealed 2,260 differentially methylated positions. The hypomethylating agent decitabine upregulated the expression of antigen-presenting machinery in MCC cell lines and stimulated membrane expression of HLA-A in VP and VN MCC xenograft tumors. Decitabine also induced prominent caspase- and large T antigen‒independent cell death in VP MCC, whereas VN MCC cell lines displayed decreased proliferation without increased cell death. In mouse xenografts, decitabine significantly decreased the size of VP tumors but not that of VN tumors. Our findings indicate that viral status predicts genomic methylation patterns in MCC and that decitabine may be therapeutically effective against MCC through antiproliferative effects, cell death, and increased immune recognition.

The Importance of Patient-Centered Care in Colon Cancer Patients With Severe Mental Illness.

There is an abundance of literature that highlights the importance of patient-centered communication with cancer patients requiring surgical intervention. While the need for communication for patients requiring surgery is well understood, less attention is brought to patients with severe mental illnesses. More literature is needed to highlight the importance and application of patient-centered care for patients suffering from both severe mental illness and cancer requiring surgical intervention. It is unclear if poor communication between patients and cancer-care specialists is part of the reason for the underlying discrepancy. Efforts to reduce this discrepancy may be worth considering as a priority for health care systems. We present a case of a 63-year-old man with schizophrenia who received a late cancer diagnosis after a missed screening, resulting in an extensive surgical resection for colon cancer. We explore the possibility of careful communication between the treating physician, patient, and patient's caretakers potentially preventing the delay in his cancer diagnosis. Effective communication is especially important with mental health patients because of its effect on long-term physical and mental outcomes. We hope to further the discussion on how to better cater to this specific population of patients undergoing cancer surgery.