Long term trends at a comprehensive cancer center during the COVID-19 pandemic.

BACKGROUND: As the ongoing public health crisis from Coronavirus Disease 2019 (COVID-19) pandemic puts strains on current models of cancer care, many health care centers had to adapt to minimize the risk of exposure and infection. The effects of the COVID-19 pandemic in a comprehensive cancer center were determined. AIMS: To measure the impact of the COVID-19 pandemic on care delivery at a comprehensive cancer center. METHODS: The number of on-site and telehealth visits (TH) were obtained from scheduling software. Multiple factors including total visits, telehealth visits, screenings for cancer diagnosis, and cancer treatments were tracked from 2 years before the pandemic onset through 2022. The length of stay (LOS) and Case Mix Index (CMI) were calculated using hospital database. RESULTS: In the third quarter of FY 2020, telehealth visits (TH) represented a fifth of total patient encounters. Cancer treatments, such as chemotherapy, radiation therapy, and surgery, decreased during the pandemic with number of surgeries being most affected (23% decrease in 2020 compared to the previous fiscal year). The average length of stay (LOS) was also longer with less discharges per given time during the pandemic. The increased LOS was related to increased severity of patient illnesses since CMI was higher. Screening mammograms decreased to a nadir of 58% in 2021 as compared to those screened in pre-pandemic fiscal years. CONCLUSION: The COVID-19 pandemic impacted many aspects of care, such as treatment and screenings. Many of these factors had to be postponed due to the fear of acquiring COVID-19 and access to care. The findings presented implicate that the delays and changes in cancer care during the pandemic resulted in less screening and treatment of more advanced disease.

Using telemedicine to facilitate social distancing in otolaryngology: A systematic review.

OBJECTIVES: As the coronavirus 2019 pandemic puts strains on current models of otolaryngology practice, telemedicine is an attractive way for otolaryngologists to reduce in-person appointments while still addressing the health of their patients. This systematic review of the literature aims to identify the evidence basis for using telemedicine in otolaryngology practice to limit person-to-person interactions while achieving comparable quality to in-person services. METHODS: The authors gathered articles from three databases (Embase, PubMed and Web of Science), performed a comprehensive literature review of articles published on telemedicine since 2002, and selected articles for inclusion based on their relevance to otolaryngology and the potential of the intervention to improve patient social distancing. RESULTS: A total of 7153 articles were identified from the initial query. After review, 35 met the inclusion criteria. Of the included articles, 32 (91%), found their specific telemedicine intervention to be effective when compared to in-person services. Twenty articles (57%) were related to remote otoscopy. Other telemedical interventions included videoconferencing for peri-operative visits, diagnosis of peritonsillar abscess, telephone-based voice evaluations and evaluation of nasal fractures. CONCLUSIONS: Video-otoscopy is the most well-supported telemedical intervention which limits physical contact between otolaryngologists and their patients. Other interventions have also demonstrated efficacy but have yet to be as widely validated as video-otoscopy. Telehealth facilitators play a key role in providing high-quality telehealth services. More invasive procedures, such as laryngoscopy, require further evidence to demonstrate definite benefits in a telemedicine setting.

African American race as a risk factor associated with a second primary lung cancer after initial primary head and neck cancer.

BACKGROUND: Initial primary head and neck cancer (IPHNC) is associated with second primary lung cancer (SPLC). We studied this association in a population with a high proportion of African American (AA) patients. METHODS: Patients with IPHNC and SPLC treated between 2000 and 2017 were reviewed for demographic, disease, and treatment-related characteristics and compared to age-and-stage-matched controls without SPLC. Logistic and Cox regression models were used to analyze the relationship of these characteristics with the development of SPLC and overall survival (OS). RESULTS: Eighty-seven patients and controls were compared respectively. AA race was associated with a significantly higher risk of developing SPLC (OR 2.92, 95% CI 1.35-6.66). After correcting for immortal time bias, patients with SPLC had a significantly lower OS when compared with controls (HR 0.248, 95% CI 0.170-0.362). CONCLUSIONS: We show that AA race is associated with an increased risk of SPLC after IPHNC; reasons of this increased risk warrant further investigation.

Telemedicine trends at a comprehensive cancer center during the first wave of the COVID-19 pandemic.

INTRODUCTION: This article reports on the effects of an early outbreak during the COVID-19 pandemic on visit volume and telehealth use by various specialists at a comprehensive cancer center. MATERIALS AND METHODS: The number of on-site and telehealth visits (THV) for medical and surgical specialties were obtained from scheduling software. RESULTS: Total visits were most drastically limited in April 2020 to a low point of 3139; THV made up 28% of all visits. For head and neck surgery, THV made up 54% and 30% of visits in April and May, respectively. Other specialties, such as psychiatry and palliative care, had higher levels of THV. For most specialties, the rebound in June through September did not make up for visits lost during the outbreak, and fiscal year  (FY) 2020 had a 9% loss from FY 2019 with 5786 fewer total annual visits across all specialties. CONCLUSIONS: While telemedicine was a helpful part of this cancer center's response to the initial COVID-19 surge, it was not able to replace the in-person services offered at the same center. The main strategy of physicians at this cancer center was to defer care, with telemedicine being an auxiliary response.

The role of immune checkpoint inhibitors in anaplastic thyroid cancer (Case Series).

Anaplastic thyroid carcinoma (ATC) is a rare type of thyroid neoplasm. However, it is one of the most aggressive forms of malignancy accounting for approximately 50% of mortality associated with all thyroid cancers. Here we report two cases of ATC treated with immune checkpoint inhibitors. Next generation sequencing identified BRAFV600E mutation in one of the patients who also derived benefit from BRAF targeted therapy. We here discuss these cases highlighting the importance of expert pathological review, utilizing molecular testing to identify the underlying genetic targets for personalized therapy, and the potential role of PD-1 inhibitors for the treatment of ATC.

Disulfiram (Antabuse) Activates ROS-Dependent ER Stress and Apoptosis in Oral Cavity Squamous Cell Carcinoma.

A paucity of advances in the development of novel therapeutic agents for squamous cell carcinomas of the head and neck, oral cavity (OSCC) and oropharynx, has stagnated disease free survival rates over the past two decades. Although immunotherapies targeted against checkpoint inhibitors such as PD-1 or CTLA-4 are just now entering the clinic for late stage disease with regularity the median improvement in overall survival is only about three months. There is an urgent unmet clinical need to identify new therapies that can be used alone or in combination with current approaches to increase survival by more than a few months. Activation of the apoptotic arm of the unfolded response (UPR) with small molecules and natural products has recently been demonstrated to be a productive approach in pre-clinical models of OSCC and several other cancers. The aim of current study was to perform a high throughput screen (HTS) with a diverse chemical library to identify compounds that could induce CHOP, a component of the apoptotic arm of the UPR. Disulfiram (DSF, also known as Antabuse) the well-known aversion therapy used to treat chronic alcoholism emerged as a hit that could generate reactive oxygen species, activate the UPR and apoptosis and reduce proliferation in OSCC cell cultures and xenografts. A panel of murine embryonic fibroblasts null for key UPR intermediates (e.g., Chop and Atf4) was resistant to DSF suggesting that an intact UPR is a key element of the mechanism regulating the antiproliferative effects of DSF.

Targeting the unfolded protein response in head and neck and oral cavity cancers.

Many FDA-approved anti-cancer therapies, targeted toward a wide array of molecular targets and signaling networks, have been demonstrated to activate the unfolded protein response (UPR). Despite a critical role for UPR signaling in the apoptotic execution of cancer cells by many of these compounds, the authors are currently unaware of any instance whereby a cancer drug was developed with the UPR as the intended target. With the essential role of the UPR as a driving force in the genesis and maintenance of the malignant phenotype, a great number of pre-clinical studies have surged into the medical literature describing the ability of dozens of compounds to induce UPR signaling in a myriad of cancer models. The focus of the current work is to review the literature and explore the role of the UPR as a mediator of chemotherapy-induced cell death in squamous cell carcinomas of the head and neck (HNSCC) and oral cavity (OCSCC), with an emphasis on preclinical studies.

Soy Isoflavone Supplementation Increases Long Interspersed Nucleotide Element-1 (LINE-1) Methylation in Head and Neck Squamous Cell Carcinoma.

AIM: Soy isoflavones have been suggested as epigenetic modulating agents with effects that could be important in carcinogenesis. Hypomethylation of LINE-1 has been associated with head and neck squamous cell carcinoma (HNSCC) development from oral premalignant lesions and with poor prognosis. To determine if neoadjuvant soy isoflavone supplementation could modulate LINE-1 methylation in HNSCC, we undertook a clinical trial. METHODS: Thirty-nine patients received 2-3 weeks of soy isoflavone supplements (300 mg/day) orally prior to surgery. Methylation of LINE-1, and 6 other genes was measured by pyrosequencing in biopsy, resection, and whole blood (WB) specimens. Changes in methylation were tested using paired t tests and ANOVA. Median follow up was 45 months. RESULTS: LINE-1 methylation increased significantly after soy isoflavone (P < 0.005). Amount of change correlated positively with days of isoflavone taken (P = 0.04). Similar changes were not seen in corresponding WB samples. No significant changes in tumor or blood methylation levels were seen in the other candidate genes. CONCLUSION: This is the first demonstration of in vivo increases in tissue-specific global methylation associated with soy isoflavone intake in patients with HNSCC. Prior associations of LINE-1 hypomethylation with genetic instability, carcinogenesis, and prognosis suggest that soy isoflavones maybe potential chemopreventive agents in HNSCC.

Recent trends in oropharyngeal cancer funding and public interest.

OBJECTIVES/HYPOTHESIS: The incidence of oropharyngeal cancer (OPC) has increased in the United States. This has been driven by an increase in human papillomavirus (HPV)-positive OPC. Our objective is to determine trends in National Institutes (NIH)-supported research funding and public interest in OPC. METHODS: The NIH Research Portfolio Online Reporting Tools database was evaluated for projects related to OPC between 2004 and 2015. Projects were evaluated for total funding, relation to HPV, principal investigator departmental affiliation and degree, and NIH agency or center responsible for grant. The Google Trends database was evaluated for relative Internet search popularity of oropharyngeal cancer and related search terms between 2004 and 2015. RESULTS: In terms of NIH funding, 100 OPC-related projects representing 242 grant years and $108.5 million were funded between 2004 and 2015. Total NIH funding for OPC projects increased from $167,406 in 2004 to $16.2 million in 2015. Funding for HPV-related OPC increased from less than $2 million yearly between 2004 and 2010 up to $12.7 million in 2015. Principal investigators related to radiation oncology ($41.8 million) and with doctor of medicine degrees ($52.8 million) received the largest share of total funding. Relative Internet search popularity for oropharyngeal cancer has increased from 2004 to 2015 compared to control cancer search terms. CONCLUSION: Increased public interest and NIH funding has paralleled the rising incidence of OPC. NIH funding has been driven by projects related to the role of HPV in OPC. LEVEL OF EVIDENCE: 2c. Laryngoscope, 127:1345-1350, 2017.

Tumor Differentiation as a Prognostic Factor for Major Salivary Gland Malignancies.

Objective The effect of tumor differentiation on prognosis of major salivary gland malignancies is controversial. The aim of this study was to determine the effect of tumor differentiation on prognosis by stage in patients with major salivary gland malignancies and to analyze which patient factors are associated with tumor differentiation. Study Design and Setting Cross-sectional analysis of Surveillance, Epidemiology, and End Results (SEER) database. Subjects and Methods In total, 9810 patients who had a major salivary gland malignancy from 2004 to 2012 were identified using the SEER database. Patients with no staging information or no information on histologic differentiation were excluded. A total of 5366 patients were included in the study. For analysis, patients were categorized by American Joint Committee on Cancer (AJCC) stage and subdivided by tumor differentiation. Multivariate analysis was used to analyze the impact of tumor differentiation on survival, tumor location (parotid, submandibular, sublingual), and sex within each AJCC stage of disease. Results Data analysis demonstrated a significant difference in histologic differentiation by stage, with P < .0001. Within stages II, III, and IV, tumor differentiation was significantly associated with a decrease in survival. There was no significant difference in tumor differentiation between the parotid and submandibular gland. Conclusion For patients with stage II, III, and IV disease, tumor differentiation was an independent predictor of survival. This information can be useful when discussing prognosis and can potentially influence management of disease.

Head and Neck Cancer.

Despite a considerable expansion in our therapeutic repertoire for management of other malignancies, mortality from head and neck cancer (HNC) has not significantly improved in recent decades. Upon normalizing National Institutes of Health-awarded R01 and R01-equivalent grants by incidence, thyroid cancer ($214) and HNC ($1329) received the fewest funding dollars. Upon adjusting funding totals by mortality, HNC was 7th out of 9 cancers evaluated ($6138). These findings highlight HNC as an underfunded disease versus other cancers. As data detailing grant applications (including unsuccessful grants) are not publicly available, it is not clear if these disparities stem from fewer applications or fewer opportunities. Our hope is that this commentary will spur further investigation into strategies to increase HNC inquiry and funding for trainees as well as early-stage and established investigators.

Outcomes of nonsurgical management of locally advanced carcinomas of the sinonasal cavity.

OBJECTIVE: To determine the outcome of definitive concurrent chemoradiation with platinum for locally advanced sinonasal carcinomas. STUDY DESIGN: Retrospective cohort. METHODS: Twenty-three nonsurgically and definitively treated patients diagnosed between July 1998 and February 2009 were analyzed. Patients with adenoid cystic carcinoma or adenocarcinoma were treated with photons and neutrons; the other histologies received photons alone. The vast majority received chemotherapy. Descriptive statistics were utilized, and Kaplan-Meier estimates were computed. RESULTS: Female (57%) and Caucasian (74%) preponderance were observed. Eighty-seven percent were unresectable; the maxillary and nasoethmoid sites were equally prevalent. Intensity-modulated radiation therapy (IMRT) and photons alone were utilized in 74% and 70%, respectively. Platinum agents were given in 95% of chemotherapy patients. Complete response was observed in 64% of patients. Median progression-free survival (PFS) and overall survival (OS) were 28.8 and 65.3 months, respectively. Three-year PFS and OS rates were 44% and 72%, respectively; 5-year PFS and OS rates were 30% and 60%, respectively. Intensity-modulated radiation therapy and a maxillary site of origin showed a trend toward superior PFS; higher-dose regimens were associated with somewhat shorter PFS. Relapse was observed in 59% of patients, predominantly local. There were few unanticipated adverse effects, and no grade IV/V events were reported. CONCLUSION: Advanced sinonasal carcinomas are chemoradiosensitive tumors, albeit with a high propensity for local relapse. There is a definite indication for IMRT and a potential curative role of platinum-based chemoradiation regimens. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:855-861, 2017.

PD1/PD-L1 inhibition as a potential radiosensitizer in head and neck squamous cell carcinoma: a case report.

BACKGROUND: Immunotherapy targeting the checkpoint PD1 (programmed cell death protein 1) or PDL1 (programmed death ligand 1) has led to advances in the treatment of melanoma and non-small cell lung cancer (NSCLC). The use of such therapies has also been introduced into the treatment of other malignancies, including head and neck cancer. The combined effects of checkpoint inhibitors and anti-PD1(L1) antibodies and radiation therapy have not yet been sufficiently investigated. CASE PRESENTATION: We report a case of locally relapsed non-resectable oral cavity squamous cell carcinoma, with excellent local control after pembrolizumab (MK3475) followed by radiotherapy. CONCLUSION: T cell activation induced by checkpoint inhibition may dramatically improve tumor response to radiation. More data are needed to identify the toxicity and efficacy of sequential or concurrent checkpoint inhibitors and radiotherapy.

Pretreatment computed tomographic gross tumor volume as predictor of persistence of tracheostomy and percutaneous endoscopic gastrostomy tube in patients undergoing larynx preservation.

BACKGROUND: Although larynx preservation affords patients improvements in laryngectomy-free survival, little has been reported regarding the functional outcomes after larynx preservation. The purpose of this study was to report the predictive value of pretreatment CT-gross tumor volume (GTV) for persistence of tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube in larynx preservation patients. METHODS: Each patient had a CT scan before initiation of therapy and the GTV was contoured. RESULTS: Using recursive partitioning analysis (RPA), threshold GTVs of 27.16 cc and 12 cc were identified for association of time with tracheostomy and PEG tube, respectively. Median (95% confidence interval [CI]) times above and below these thresholds were 1.84 (1.06-not reached [NR]) and 0.75 (0.63-1.26) years, respectively (p = .03) for time with tracheostomy and 1.75 (1.34-NR) and 0.84 (0.46-NR) years, respectively (p = 0.10) for time with PEG tube. CONCLUSION: This study demonstrates that pretreatment CT-GTV is predictive of an approximately 2.5-fold and approximately 2-fold, respectively, increase in time with tracheostomy and PEG tube. © 2016 Wiley Periodicals, Inc. Head Neck 38: First-1458, 2016.

Borrelidin Induces the Unfolded Protein Response in Oral Cancer Cells and Chop-Dependent Apoptosis.

Oral squamous cell carcinoma (OSCC) is the most common cancer affecting the oral cavity, and US clinics will register about 30,000 new patients in 2015. Current treatment modalities include chemotherapy, surgery, and radiotherapy, which often result in astonishing disfigurement. Cancers of the head and neck display enhanced levels of glucose-regulated proteins and translation initiation factors associated with endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). Previous work demonstrated that chemically enforced UPR could overwhelm these adaptive features and selectively kill malignant cells. The threonyl-tRNA synthetase (ThRS) inhibitor borrelidin and two congeners were discovered in a cell-based chemical genomic screen. Borrelidin increased XBP1 splicing and led to accumulation of phosphorylated eIF2α and UPR-associated genes, prior to death in panel of OSCC cells. Murine embryonic fibroblasts (MEFs) null for GCN2 and PERK were less able to accumulate UPR markers and were resistant to borrelidin. This study demonstrates that UPR induction is a feature of ThRS inhibition and adds to a growing body of literature suggesting ThRS inhibitors might selectively target cancer cells.

Understanding the Risk Factors and Long-Term Consequences of Cisplatin-Associated Acute Kidney Injury: An Observational Cohort Study.

Acute kidney injury (AKI) is a well-known complication of cisplatin-based chemotherapy; however, its impact on long-term patient survival is unclear. We sought to determine the incidence and risk factors for development of cisplatin-associated AKI and its impact on long-term renal function and patient survival. We identified 233 patients who received 629 cycles of high-dose cisplatin (99±9mg/m2) for treatment of head and neck cancer between 2005 and 2011. These subjects were reviewed for development of AKI. Cisplatin nephrotoxicity (CN) was defined as persistent rise in serum creatinine, with a concomitant decline in serum magnesium and potassium, in absence of use of nephrotoxic agents and not reversed with hydration. All patients were hydrated per protocol and none had baseline glomerular filtration rate (GFR) via CKD-EPI<60mL/min/1.73m2. The patients were grouped based on development of AKI and were staged for levels of injury, per KDIGO-AKI definition. Renal function was assessed via serum creatinine and estimated glomerular filtration rate (eGFR) via CKD-EPI at baseline, 6- and 12-months. Patients with AKI were screened for the absence of nephrotoxic medication use and a temporal decline in serum potassium and magnesium levels. Logistic regression models were constructed to determine risk factors for cisplatin-associated AKI. Twelve-month renal function was compared among groups using ANOVA. Kaplan-Maier curves and Cox proportional hazard models were constructed to study its impact on patient survival. Of 233 patients, 158(68%) developed AKI; 77 (49%) developed stage I, 55 (35%) developed stage II, and 26 (16%) developed stage III AKI. Their serum potassium and magnesium levels correlated negatively with level of injury (p<0.05). African American race was a significant risk factor for cisplatin-associated AKI, OR 2.8 (95% CI 1.3 to 6.3) and 2.8 (95% CI 1.2 to 6.7) patients with stage III AKI had the lowest eGFR value at 12 months (p = 0.05) and long-term patient survival (HR 2.1; p<0.01) than patients with no or lower grades of AKI. Most common causes of death were recurrent cancer (44%) or secondary malignancy elsewhere (40%). Cisplatin-associated severe AKI occurs in 20% of the patients and has a negative impact on long-term renal function and patient survival. PEG tube placement may be protective and should be considered in high risk-patients.

Biweekly gemcitabine and paclitaxel in patients with relapsed or metastatic squamous cell carcinoma of the head and neck.

PURPOSE: We conducted a Phase II, clinical trial to evaluate the efficacy and safety of a biweekly gemcitabine and paclitaxel (GEMTAX) regimen as second-line treatment in patients with recurrent or metastatic unresectable, squamous cell carcinoma of the head and neck (SCCHN). The primary endpoint was response rate. PATIENTS AND METHODS: Patients with recurrent unresectable or metastatic platinum refractory SCCHN, who had performance status ≤2 and adequate organ function, were eligible. Gemcitabine (3000 mg/m(2) intravenous) and paclitaxel (150 mg/m(2) intravenous) was given on days 1 and 15of 4 weeks cycle, until patients had disease progression or unacceptable toxicity. RESULTS: Disease control (partial response [PR] + complete response [CR] + stable disease [SD]) was noted in 19 patients (54%) and overall response (CR + PR) was noted in 8 patients (23%). However, the most frequent response outcomes were progressive disease in 16 patients (46%) and SD in 11 patients (31%). The most frequent Grade 3-4 adverse events were lymphopenia in 38 patients (75%), anemia in 20 patients (39%), and infection in 16 patients (31%). Median progression-free survival was 3.6 months; median overall survival was 6.3 months. CONCLUSION: The biweekly GEMTAX regimen has statistically significant grade 3 and 4 adverse events and has meaningful clinical activity as a second-line treatment in patients with recurrent or metastatic SCCHN who have received prior chemotherapy. This regimen may particularly be a useful treatment option in patients who progressed in less than 6 months of concurrent chemoradiotherapy with high-dose cisplatin and/or have recurrent/metastatic platinum refractory SCCHN.

Transoral robotic surgery for treatment of obstructive sleep apnea: factors predicting surgical response.

OBJECTIVES/HYPOTHESIS: We reviewed our experience with the use of transoral robotic surgery (TORS) for base of tongue (BOT) reduction either alone or as part of multilevel strategy in the treatment of obstructive sleep apnea/hypopnea syndrome (OSAHS) in order to identify clinical characteristics that may be associated with surgical response. STUDY DESIGN: Case series. METHODS: Between June 2010 and May 2014, BOT reduction via TORS ± partial epiglottectomy ± uvulopalatopharyngoplasty were performed on 72 patients with OSAHS. Thirty-nine patients (15 females and 24 males) with complete preoperative and postoperative clinical information including polysomnograms were included in this study. RESULTS: Mean apnea-hypopnea index (AHI) was 43.9 ± 32.3 preoperatively and 21.9 ± 23.5 postoperatively and reflected a statistically significant (P < 0.001) AHI reduction of 50.9% ± 38.1%. Statistical significant reduction in daytime somnolence, as measured by Epworth Sleepiness Scale (15.6 ± 5.4 preoperatively vs. 5.7 ± 4.3 postoperatively; P < 0.001), was also achieved. No statistical significant difference was found between preoperative and postoperative body mass index (BMI) (32.9 ± 7.0 vs. 32.4 ± 7.3; P = 0.270). Surgical response, as defined by > 50% reduction in AHI and final AHI < 15 with resolution of daytime somnolence, was achieved in 21 patients (53.8%). Clinical characteristics found to be significantly different between the responders and nonresponders were BMI, AHI, and lateral velopharyngeal collapse. Patients with BMI < 30, AHI < 60, or absence of lateral velopharyngeal collapse have excellent surgical response rate of 88.2%, 67.9%, or 66.7%, respectively. CONCLUSIONS: We identified three clinical characteristics associated with increased surgical response rate. This finding may be useful for patient selection and counseling prior to surgery.

Risk stratification based on thyroid cytology: can we rely on national data?

PURPOSE: Determine correlation of malignancy rates between fine needle aspiration (FNA) biopsy and surgical specimen in an urban academic environment. METHODS: Retrospective review at an academic medical center of fine needle aspiration biopsies and surgical specimens in a head and neck otolaryngology practice between 2000 and 2012. RESULTS: Of the 74 biopsies diagnosed as follicular lesion, 34 (45.9%) were malignant. Of the 45 biopsies diagnosed as follicular neoplasm, 22 (48.9%) were malignant. These results are significantly higher than the average risk of malignancy cited by the American Thyroid Association of 5%-10% and 20%-30% for follicular lesions and neoplasms respectively. CONCLUSIONS: The rate of malignancy based on a FNA diagnosis of indeterminate cytology (follicular lesion or follicular neoplasm) can vary greatly among different institutions. Thyroid surgeons should be aware of their local pathology practices to better guide therapy and counsel patients.