27-gene Immuno-Oncology (IO) Score is Associated With Efficacy of Checkpoint Immunotherapy in Advanced NSCLC: A Retrospective BC Cancer Study.

BACKGROUND: Immune checkpoint inhibitors (ICI) are standard of care in advanced non-small cell lung cancer (NSCLC). However, not all patients benefit, even among PD-L1 tumor proportional score (TPS) ≥50%, indicating an unmet need for additional biomarkers such as those assessing the tumor immune microenvironment (TIME). DetermaIO is a 27-gene assay that classifies TIME and has previously demonstrated association with ICI response. METHODS: FFPE samples were selected from BC Cancer and West Clinic Cancer Center patients with performance status (PS) ≤2 who received at least 2 cycles of ICI monotherapy in the first (1L) or second line (2L). IO scores were generated and analyzed for association with PFS and OS. RESULTS: In the entire cohort (N=147), IO score was significantly associated with OS (HR=0.68, 95%CI 0.47-0.99, P = .042) and PFS (HR=0.62, 95%CI 0.43-0.88, P = .0069). In 1L treated patients (PD-L1≥50%, N=78), IO score was significantly associated with PFS (HR=0.55, 95%CI 0.32-0.94, P = .028). In exploratory analyses, IO score was associated with benefit in 1L PS2 patients for OS (HR = 0.26, 95%CI 0.091-0.74, P = .012) and PFS (HR = 0.27, 95%CI 0.098-0.72, P = .0095) which was confirmed in PFS subgroup analysis in the independent West Cancer Center study (N=13 HR=0.14, 95%CI 0.027-0.76, P = .023). CONCLUSION: These data confirm the association of DetermaIO with ICI clinical benefit in NSCLC, and expand on previous studies by demonstrating that first line treated PD-L1≥50% patients can further be stratified by IO score to identify efficacy. Exploratory analysis suggested that the IO score identifies benefit in patients with poor PS.

Association of a novel 27-gene immuno-oncology assay with efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitor (ICI) therapies represent a major advance in treating a variety of advanced-stage malignancies. Nevertheless, only a subset of patients benefit, even when selected based on approved biomarkers such as PD-L1 and tumor mutational burden. New biomarkers are needed to maximize the therapeutic ratio of these therapies. METHODS: In this retrospective cohort, we assessed a 27-gene RT-qPCR immuno-oncology (IO) gene expression assay of the tumor immune microenvironment and determined its association with the efficacy of ICI therapy in 67 advanced-stage NSCLC patients. The 27-gene IO test score (IO score), programmed cell death ligand 1 immunohistochemistry tumor proportion score (PD-L1 TPS), and tumor mutational burden (TMB) were analyzed as continuous variables for response and as binary variables for one-year progression free survival. The threshold for the IO score was prospectively set based upon a previously described training cohort. Prognostic implications of the IO score were evaluated in a separate cohort of 104 advanced-stage NSCLC patients from The Cancer Genome Atlas (TCGA) who received non-ICI therapy. RESULTS: The IO score was significantly different between responders or non-responders (p = 0.007) and associated with progression-free survival (p = 0.001). Bivariate analysis established that the IO score was independent of PD-L1 TPS and TMB in identifying patients benefiting from ICI therapy. In a separate cohort of late-stage NSCLC patients from TCGA, the IO score was not prognostic of outcome from non-ICI-treated patients. CONCLUSIONS: This study is the first application of this 27-gene IO RT-qPCR assay in a clinical cohort with outcome data. IO scores were significantly associated with response to ICI therapy and prolonged progression-free survival. Together, these data suggest the IO score should be further studied to define its role in informing clinical decision-making for ICI treatment in NSCLC.

Renal Cell Carcinoma Presenting With Combined Cervical Lymphadenopathy and Cardiac Metastasis Without Inferior Vena Cava Involvement.

Renal cell cancer is the third most common urological malignancy following prostate and bladder malignancies. Cardiac metastases to the right side of the heart without inferior vena cava (IVC) involvement are exceedingly rare, with only a handful of cases described in the literature. Metastasis to the head and neck region is also rare, occurring in an estimated 1% of cases. Here we present a case of a patient with recurrent syncopal events secondary to renal cell carcinoma without IVC involvement, with metastases both to the right ventricle and cervical lymph nodes. To our knowledge, this is the first case that presents with both of these rare findings together and that highlights cancer screening in patients with high risk factors and new exam findings in patients with syncopal events having negative initial workup.

Association Between Pesticide Use and Incidence of Diffuse Large B-Cell Lymphoma.

BACKGROUND/AIM: Exposure to pesticides has been reportedly associated with several types of cancer. MATERIALS AND METHODS: In this study, we used data from The United States Geological Survey (USGS), United States Census, and the Surveillance, Epidemiology, and End Results (SEER) database to analyze the association between the area density of specific agricultural pesticides and the county level annual incidence of diffuse large B-cell lymphoma (DLBCL). RESULTS: Incidence of DLBCL was significantly associated with an area density of 14 of the pesticides reported by USGS. CONCLUSION: This highlights the need for further investigation into the safety of the use of these pesticides. The importance of this study comes not only from the significant association it shows between pesticides and the incidence of cancer, but also from the fact that it included all compounds reported to USGS as being used in agriculture. This helps in prioritizing pesticides for further evaluation.

A Case Report of Disseminated Blastomycosis With Thyroid Involvement in a Pregnant Patient.

Blastomyces dermatitidis is the causal agent of blastomycosis, an invasive and often serious fungal infection. Blastomycosis typically presents as a pulmonary infection, but common extrapulmonary manifestations of blastomycosis include the skin, bones, and reticuloendothelial systems. Disseminated blastomycosis occurs more prominently in immunocompromised individuals, such as organ transplant recipients, HIV patients, and pregnant women. We report here a rare case of disseminated blastomycosis to the thyroid in a pregnant patient. This case emphasizes the unique challenges of diagnosing and treating disseminated fungal infections in pregnancy.

Usefulness of patient-reported outcomes to assess the effectiveness of topical hormonal therapy for gynecologic symptoms after antihormonal treatment for breast cancer.

The aim of this retrospective study was to assess the efficacy of topical hormonal therapy (THT) to relieve vaginal symptoms resulting from antihormonal therapy in women with hormone receptor-positive breast cancer. A total of 74 breast cancer patients who received THT for vaginal complaints were retrospectively identified and statistically matched with 74 control breast cancer patients with vaginal complaints with no documented use of THT. Symptom scores were recorded from the center's proprietary patient-reported outcomes database, Patient Care Monitor (ConcertoHealthAI, Boston). A baseline score was noted at the initiation of antihormonal therapy and was followed at 6 and 12 months. The median differences between baseline, 6-month, and 12-month scores were analyzed. Repeated measures analysis of variance assessed the impact of topical hormonal replacement. There was no statistically significant difference in score change between the two groups at 6 and 12 months. In the active THT group, there were no statistically significant differences in vaginal complaints or sexual problems over time: {F (2, 146) = 0.99, P = 0.369; and F (2, 146) = 1.56, P = 0.217}, respectively. In this study, the use of topical hormonal replacement was not effective in alleviating vaginal symptoms.

Hyperammonemic encephalopathy associated with 5-fluorouracil in a patient with previous orthotopic liver transplantation.

5-Fluorouracil (5-FU)-based chemotherapy is the most common regimen used to treat metastatic or advanced colon cancer. Neurotoxicity is a rare but serious adverse effect of 5-FU-based therapy. We report an unusual case of 5-FU-induced hyperammonemic encephalopathy in a patient with recurrent colon cancer that metastasized to the liver and lung. Two days after receiving the third dose of FOLFOX, he presented with altered mental status, agitation, abdominal pain, nausea, and vomiting. His total ammonia level was 434 µmol/L, for which he was treated with lactulose retention enema and lactulose via nasogastric tube. Over the next 24 hours, his condition improved significantly.

Unusual recurrent metastasizing benign breast papilloma: a case report.

BACKGROUND: Papillary breast lesions may be benign, atypical, and malignant lesions. Pathological and clinical differentiation of breast papillomas can be a challenge. Unlike malignant lesions, benign breast papillomas are not classically associated with lymph node and distant metastasis. We report a unique case of a recurrent, benign breast papilloma presenting as an aggressive malignant tumor. CASE PRESENTATION: Our patient was a 56-year-old postmenopausal African American woman who was followed in the breast clinic with a long history of multiple breast papillomas. She underwent multiple resections over the course of 7-9 years. After being lost to follow-up for 2 years, she once again presented with a slowly enlarging left breast mass. Subsequent imaging revealed a predominantly cystic mass in the left breast, as well as a suspicious hypermetabolic internal mammary node and a hypermetabolic nodule in the pretracheal space. Biopsy of the internal mammary node demonstrated papillary neoplasm with benign morphology and immunostains positive for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2/Neu. Due to the clinical picture concerning for malignancy, the patient was then started on endocrine therapy with palbociclib and letrozole before surgery. She then underwent simple mastectomy and sentinel lymph node dissection with negative nodes and pathology once again revealing benign papillary neoplasm. She underwent adjuvant chest wall radiation for 6 weeks and received letrozole following completion of her radiation therapy. She was without evidence of disease 30 months after surgery. CONCLUSIONS: We present an unusual case of multiple recurrent peripheral papillomas with entirely benign histologic features exhibiting malignant behavior over a protracted period of many years, with an invasion of pectoralis musculature and possibly internal mammary and mediastinal nodes. Her treatment course included multiple surgeries (ultimately mastectomy), radiation therapy, and endocrine therapy.

Oral potentially malignant disorders: clinical diagnosis and current screening aids: a narrative review.

Around 300 000 patients are estimated to have oral cancer worldwide annually, and the incidence is higher in South Asian countries. In 2005, at the Congress of WHO, the term potentially malignant disorder (PMD)/lesion was suggested as a replacement for premalignant oral lesions and conditions. PMDs are those lesions of the oral mucosa that are at an increased risk of malignant transformation compared with the healthy mucosa. PMDs consist of leukoplakia, erythroplakia, oral lichen planus, oral submucous fibrosis, and other miscellaneous lesions. A literature search was performed using PubMed, Scopus, and Web of Science without any language restrictions. There is no standardized method for identifying a site for biopsy and various methods such as toluidine blue stain, methylene blue, Lugol's iodine, and chemiluminescence have been proposed in the literature. Despite easy access to the oral cavity, there has been significant mortality associated with oral cancer as they are often diagnosed late because of the inability of healthcare professionals to identify them at early premalignant states. This article aims to provide healthcare professionals with the knowledge to identify potentially malignant disorders and to aid them in biopsy site identification.

Hypogonadism and prostate cancer detection on multiparametric MRI and mpMRI-TRUS fusion biopsy.

PURPOSE: Currently, there is a dearth of data concerning the impact of hypogonadism on prostate cancer detection by imaging. In this study, we evaluated the performance of multiparametric MRI (mpMRI) and mpMRI-TRUS fusion biopsy in hypogonadal patients. MATERIALS AND METHODS: Clinical and pathologic data from a prospectively maintained, single-institution database of patients who underwent 3T mpMRI and fusion biopsy between 2007 and 2016 were analyzed. Hypogonadism was defined by an institutional cutoff of serum testosterone ≤ 180 ng/dL; T2, DWI, and DCE scores were calculated from mpMRI. Cancer detection rates were compared by Chi-square tests. Multivariate logistic regression was undertaken to evaluate the impact of hypogonadism on clinically significant cancer detection by systematic and fusion biopsy. RESULTS: We included 522 patients in our study who had total testosterone levels measured within 90 days of mpMRI. Of these, 49 (9.4%) were hypogonadal. Median total testosterone was 148 ng/dL (IQR 41) in the hypogonadal group, and 304 ng/dL (IQR 132) in the normogonadal group (p < 0.001). Imaging results were comparable between the hypo and normogonadal groups. In the hypogonadal group, systematic biopsy detected clinically significant cancer in 28.6% of patients compared to 40.8% with fusion biopsy. In the normogonadal cohort, systematic and fusion biopsy detected 37.3% and 43.2% CS cancer, respectively. In the hypogonadal cohort, fusion biopsy detected 12.2% more CS cancers compared to systematic biopsy, while it detected only 5.9% more in the normogonadal cohort. On multivariate analysis, hypogonadism was found to be an independent predictor of decreased CS cancer detection on systematic (p = 0.048), but not on fusion biopsy (p = 0.170). CONCLUSIONS: Hypogonadism is an independent predictor of lower CS cancer detection on systematic biopsy. However, it fails to significantly impact CS detection on fusion biopsy with comparable cancer detection rates in both groups. Patients with hypogonadism may benefit more from fusion biopsy than normogonadal patients.

Role of Positron Emission Tomography Imaging in Metabolically Active Renal Cell Carcinoma.

PURPOSE OF REVIEW: The clinical role of fluorine-18 fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET) in renal cell carcinoma (RCC) is still evolving. Use of FDG PET in RCC is currently not a standard investigation in the diagnosis and staging of RCC due to its renal excretion. This review focuses on the clinical role and current status of FDG PET and PET/CT in RCC. RECENT FINDINGS: Studies investigating the role of FDG PET in localized RCC were largely disappointing. Several studies have demonstrated that the use of hybrid imaging PET/CT is feasible in evaluating the extra-renal disease. A current review of the literature determines PET/CT to be a valuable tool both in treatment decision-making and monitoring and in predicting the survival in recurrent and metastatic RCC. PET/CT might be a viable option in the evaluation of RCC, especially recurrent and metastatic disease. PET/CT has also shown to play a role in predicting survival and monitoring therapy response.

Index tumor volume on MRI as a predictor of clinical and pathologic outcomes following radical prostatectomy.

PURPOSE: Index tumor volume (ITV) measured on radical prostatectomy (RP) specimens has been shown to be associated with adverse pathologic and oncologic outcomes. We evaluate the value of ITV calculated from prostate multiparametric MRI (mpMRI) in predicting adverse clinical and pathologic outcomes. MATERIALS AND METHODS: Data from a prospectively maintained, single-institution database were analyzed for patients who underwent mpMRI prior to RP (2007-2016). Index tumor was defined as a T2-visible lesion with the longest diameter. Adverse pathologic outcomes were extraprostatic extension (EPE), lymph node invasion (LNI), seminal vesicle invasion (SVI), and positive margins (PM). Logistic and Cox proportional hazard regression were used to assess associations with adverse pathology and biochemical recurrence (BCR), respectively. RESULTS: Of the 455 patients included, EPE, LNI, SVI and PM were present in 23.5%, 6.2%, 5.5% and 15.7% patients, respectively. Patients with adverse pathologic outcomes had larger median ITV. ITV was found to be an independent predictor of EPE (OR 1.22, p = 0.010), LNI (OR 1.39, p = 0.001), and SVI (OR 1.28, p = 0.009), but not PM (OR 1.03, p = 0.522). Combination of ITV and PSA was found to have predictive ability comparable to that of modified Partin tables (EPE:ITV + PSAAUC = 0.71 vs. PartinAUC = 0.71; LNI:ITV + PSAAUC = 0.92 vs. PartinAUC = 0.90, SVI:ITV + PSAAUC = 0.78 vs. PartinAUC = 0.82). 5 year BCR-free survival (median follow-up 24.9 months) was higher for patients with ITV < 2 cc (84.1% vs. 58.5%, p = 0.001). However, ITV was not found to be an independent predictor of BCR (HR 1.69, p = 0.130). CONCLUSIONS: We demonstrate that ITV measured on mpMRI is a predictor of adverse pathologic and clinical outcomes and can aid in preoperative risk assessment.

Analyzing the current practice patterns and views among urologists regarding focal therapy for prostate cancer.

INTRODUCTION AND OBJECTIVE: Focal therapy (FT) for localized prostate cancer (CaP) has been shown to have encouraging short-term oncological outcomes, excellent preservation of functional outcomes and is increasing in popularity in urologic community. We aim to evaluate the preferences and practice trends among urologists regarding this treatment strategy. METHODS: A 20 item online questionnaire was designed to collect information on urologists' views and use of FT. The survey was sent to the members of the Endourological Society and the American Urological Association. Multivariate logistic regression analysis was done to determine predictors for utilization of FT. RESULTS: A total of 425 responses were received [American Urological Association: 319, Endourological Society: 106]. Mean age of respondents was 53(SD: 11.3) years. Although half of the respondents (50.8%) believed FT to be moderate to extremely beneficial in the treatment of CaP, only 24.2% (103) of the respondents currently utilize FT in their practice. Respondents who were fellowship trained in urologic oncology were more likely to consider FT to be at least moderately beneficial (P < 0.001). Surgeon's experience (greater than 15 years in urology practice) (P = 0.025) and seeing more than 10 patients with new CaP diagnosis per month (P = 0.002) were independent predictors of FT utilization for localized CaP. While the most common setting for utilization of FT was in patients with unilateral intermediate-risk (72.8%) CaP, a small percentage of respondents also used FT for patients with unilateral high-risk CaP and bilateral intermediate risk (21.4% and 10.7%, respectively). Most common reasons for not using FT were the lack of belief in 'index lesion theory' (63.2%), lack of experience (41.3%), lack of belief in FT's efficacy (41.1%), lack of infrastructure (35.8%), difficult salvage treatment in cases of recurrence (22.7%) and high cost (21.8%). About 57.6% would use FT more often in an office or outpatient setting if they had access to reliable and cost-effective options. CONCLUSIONS: Only a quarter of our respondents utilize FT in their practice with surgeon's experience being the important independent predictor for using FT. Majority of respondents though consider FT to be beneficial in CaP management, would use it more often if provided more reliable and cost-effective options. Over time, experience and accessibility to reliable methods to perform FT may lead to further utilization of this novel treatment strategy.

Lymph node dissection during radical cystectomy following prior radiation therapy: results from the SEER database.

PURPOSE: Population studies of patients undergoing radical cystectomy (RC) for bladder cancer (BC) suggest that a more extended lymph node dissection (LND) increases survival. However, information regarding LNDs of patients undergoing RC with a history of radiation therapy for BC is largely unknown. This study aims to define the lymph node yield (LNY) in patients undergoing RC for BC following radiation of the bladder using the surveillance epidemiology and end results (SEER) database. METHODS: Data were collected using SEER 18 registries from 1988 to 2013 to identify patients undergoing RC for BC. Data on extent and yield of LND were obtained. Logistic regression and multivariate Cox proportional hazard regression were done to identify predictors of adequate LND and all-cause mortality, respectively. RESULTS: In total, 27,451 patients were identified, of which, 27,362 (99.7%) were radiation naïve and 89 (0.3%) had prior radiation therapy for BC. The average LNY in radiation naïve patients (15, SD [13.5]) was slightly higher than the LNY in patients with prior radiation (12.3 SD [9.2], p = 0.157). Prior radiation was not an independent predictor of overall mortality (HR = 1.3, 95% CI [0.98-1.7]; p = 0.076). CONCLUSIONS: A lower proportion of patients with a history of radiation underwent a LND. The LNYs of radiation naïve patients, and those with a history of radiation, were not statistically different; however, the proportion of irradiated patients was small. Further investigation will be required to elucidate the patient and provider characteristics that contribute to the similar LNYs.

Risk of Upgrading from Prostate Biopsy to Radical Prostatectomy Pathology-Does Saturation Biopsy of Index Lesion during Multiparametric Magnetic Resonance Imaging-Transrectal Ultrasound Fusion Biopsy Help?

PURPOSE: We sought to determine whether saturation of the index lesion during magnetic resonance imaging-transrectal ultrasound fusion guided biopsy would decrease the rate of pathological upgrading from biopsy to radical prostatectomy. MATERIALS AND METHODS: We analyzed a prospectively maintained, single institution database for patients who underwent fusion and systematic biopsy followed by radical prostatectomy in 2010 to 2016. Index lesion was defined as the lesion with largest diameter on T2-weighted magnetic resonance imaging. In patients with a saturated index lesion transrectal fusion biopsy targets were obtained at 6 mm intervals along the long axis of the index lesion. In patients with a nonsaturated index lesion only 1 target was obtained from the lesion. Gleason 6, 7 and 8-10 were defined as low, intermediate and high risk, respectively. RESULTS: Included in the study were 208 consecutive patients, including 86 with a saturated and 122 with a nonsaturated lesion. Median patient age was 62.0 years (IQR 10.0) and median prostate specific antigen was 7.1 ng/ml (IQR 8.0). The median number of biopsy cores per index lesion was higher in the saturated lesion group (4 vs 2, p <0.001). The risk category upgrade rate from systematic only, fusion only, and combined fusion and systematic biopsy results to prostatectomy was 40.9%, 23.6% and 13.8%, respectively. The risk category upgrade from combined fusion and systematic biopsy results was lower in the saturated than in the nonsaturated lesion group (7% vs 18%, p = 0.021). There was no difference in the upgrade rate based on systematic biopsy between the 2 groups. However, fusion biopsy results were significantly less upgraded in the saturated lesion group (Gleason upgrade 20.9% vs 36.9%, p = 0.014 and risk category upgrade 14% vs 30.3%, p = 0.006). CONCLUSIONS: Our results demonstrate that saturation of the index lesion significantly decreases the risk of upgrading on radical prostatectomy by minimizing the impact of tumor heterogeneity.