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BACKGROUND: The radiation dose to dysphagia and aspiration-related structures (DARS) for patients undergoing transoral robotic surgery (TORS) and post-operative radiation therapy (PORT) for primary oropharyngeal carcinoma is unknown. METHODS: This prospective study measured swallowing using the MD Anderson Dysphagia Inventory at baseline and then 12-months after PORT. Dosimetric parameters were collected. RESULTS: 19 patients were recruited between 2017 and 2019. Worse swallow function at 12-months after PORT was associated with dose-parameters to the oesophageal inlet muscle, superior pharyngeal constrictor muscle and cervical oesophagus. Mean dose, V50Gy, and V60Gy to the base of tongue and pharyngeal constrictors was significantly lower in those receiving PORT to the neck alone. CONCLUSION: Dose to DARS was lower in patients who received PORT to the neck alone. In patients treated with TORS and PORT, poorer swallowing outcomes at 12 months post-treatment were associated with increased dose to oesophageal inlet muscle, superior constrictor muscle, and cervical oesophagus.
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STUDY DESIGN: Case report. Osteoradionecrosis (ORN) of the jaw is a potentially devastating consequence of head and neck irradiation. The progression of ORN can lead to loss of bone, teeth, soft tissue necrosis, pathologic fracture, and oro-cutaneous fistula. Reconstructive surgery has mostly been reserved for late-stage disease where segmental resections are frequently necessary. Evidence is emerging to support earlier treatment in the form of debridement in combination with soft tissue free flaps for intermediate-stage ORN. The authors present a case of a 76-year-old male with persistent Notani 2 ORN of the mandible, treated with surgical removal of all remaining mandibular teeth, transoral debridement of all necrotic mandibular bone, and bone coverage with a left medial femoral condyle (MFC) periosteal free flap based on the descending genicular artery. Treatment was uneventful both intraoperatively and postoperatively. Since surgery (15 mo) the patient has remained free from clinical and radiologic signs of ORN. The MFP periosteal free flap provided an excellent result with minimal surgical complexity and morbidity in this case. Such treatment at an intermediate stage likely results in a reduction in segmental resections, less donor site morbidity, less operative time, less overall treatment time, and possibly fewer postoperative complications compared with the status quo.
Subject(s)
Debridement , Free Tissue Flaps , Osteoradionecrosis , Humans , Male , Osteoradionecrosis/surgery , Aged , Femur/surgery , Mandibular Diseases/surgery , Periosteum/surgery , Plastic Surgery Procedures/methods , Tooth ExtractionABSTRACT
The long-standing divide in Australia between medicine and dentistry has left many with inequitable access to dental care. People with oral cancer, in particular, may have few options for dental rehabilitation after cancer treatment, even with private health insurance. However, 2024 could finally see health care reforms that address these inequities, with significant momentum building in Australia. In this Perspective, we argue for a national approach to reforms that incorporate aspects of preventive health, primary health care, Medicare Benefits Schedule item review, and the value of Private Health Insurance rebates for dental care.
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Squamous cell carcinoma is the most common head and neck malignancy arising from the oral mucosa and the skin. The histologic and immunohistochemical features of oral squamous cell carcinoma (OSCC) and head and neck cutaneous squamous cell carcinoma (HNcSCC) are similar, making it difficult to identify the primary site in cases of metastases. With the advent of immunotherapy, reliable distinction of OSCC and HNcSCC at metastatic sites has important treatment and prognostic implications. Here, we investigate and compare the genomic landscape of OSCC and HNcSCC to identify diagnostically useful biomarkers. Whole-genome sequencing data from 57 OSCC and 41 HNcSCC patients were obtained for tumor and matched normal samples. Tumor mutation burden (TMB), Catalogue of Somatic Mutations in Cancer (COSMIC) mutational signatures, frequent chromosomal alterations, somatic single nucleotide, and copy number variations were analyzed. The median TMB of 3.75 in primary OSCC was significantly lower (P < .001) than that of 147.51 mutations/Mb in primary HNcSCC. The COSMIC mutation signatures were significantly different (P < .001) between OSCC and HNcSCC. OSCC showed COSMIC single-base substitution (SBS) mutation signature 1 and AID/APOBEC activity-associated signature 2 and/or 13. All except 1 HNcSCC from hair-bearing scalp showed UV damage-associated COSMIC SBS mutation signature 7. Both OSCC and HNcSCC demonstrated a predominance of tumor suppressor gene mutations, predominantly TP53. The most frequently mutated oncogenes were PIK3CA and MUC4 in OSCC and HNcSCC, respectively. The metastases of OSCC and HNcSCC demonstrated TMB and COSMIC SBS mutation signatures similar to their primary counterparts. The combination of high TMB and UV signature in a metastatic keratinizing squamous cell carcinoma suggests HNcSCC as the primary site and may also facilitate decisions regarding immunotherapy. HNcSCC and OSCC show distinct genomic profiles despite histologic and immunohistochemical similarities. Their genomic characteristics may underlie differences in behavior and guide treatment decisions in recurrent and metastatic settings.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Skin Neoplasms , Humans , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Squamous Cell Carcinoma of Head and Neck/genetics , DNA Copy Number Variations , Mouth Neoplasms/pathology , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Head and Neck Neoplasms/genetics , Mutation , Genomics , Biomarkers, Tumor/geneticsABSTRACT
PURPOSE: The human papillomavirus (HPV) is well recognised as a factor in developing oropharyngeal cancer (OPC). A booklet for HPV-OPC patients aimed to deliver evidence-based messages in everyday language, in a way to minimise negative psychological impacts on patients. Our study explored the suitability of the booklet for use. METHODS: Participants were recruited through social media and interviewed via Zoom. Participants were shown the booklet and a think-aloud method elicited real-time reactions to the content. Responses were analysed for each section and coded as either for or against for content, with other responses thematically analysed using NVivo. RESULTS: The sample comprised 24 participants: patients (n = 19) who completed treatment for HPV-OPC and partners of survivors of HPV-OPC (n = 5). All participants found the booklet useful, and most wished the resource had been available previously. Some indicated the information was new to them. The majority agreed the booklet would be best delivered by their specialist at point of diagnosis and would be a useful resource for friends and family. Most participants gave feedback on improvements to the booklet in terms of comprehension and design. Overall, participants found the content easy to understand. Most participants found that it helped to reduce shame and stigma associated with HPV as a sexually transmitted infection. CONCLUSION: An evidence-based booklet for HPV-OPC patients and their partners is acceptable. Implementation may be feasible in routine clinical practice, specifically at time of diagnosis. Adapting the content will help optimise the efficacy of the booklet in facilitating communication between all stakeholders.
Subject(s)
Oropharyngeal Neoplasms , Papillomavirus Infections , Humans , Human Papillomavirus Viruses , Papillomavirus Infections/complications , Oropharyngeal Neoplasms/therapy , Oropharyngeal Neoplasms/psychologyABSTRACT
The workflow for a prefabricated prelaminated fibula free flap has been almost entirely digitized. One of the last 2 remaining steps is the impression making in stage 1 surgery. This article describes a novel computed-tomography based digital scanning technique with an assessment of the resultant accuracy.
Subject(s)
Free Tissue Flaps , Workflow , Fibula/diagnostic imaging , Fibula/surgery , Maxilla/surgery , Dental Impression TechniqueABSTRACT
BACKGROUND: Substantial variation exists in how well health care is integrated, even across similarly structured organizations, yet research about what physician organizations (POs) do that enables or inhibits integrated care is limited. PURPOSE: The aim of this study was to explore the dynamics that enable POs to integrate care. METHODOLOGY/APPROACH: We ranked a stratified sample of POs according to patient perceptions of integrated care, as measured in a survey. We interviewed professionals, patients, and family members in 10 higher and 3 lower ranked POs about the process of caring for patients with complex conditions. We derived integration-related themes from the interview data and quantified their prevalence. Using a quasi-statistical approach, we explored relationships among themes and their associations with patient perceptions of integrated care. RESULTS: From 6,104 coded references, we derived a set of themes representing integration perspectives, integration engagement mechanisms, and integration failures. POs experienced frequent integration failures. Higher ranked POs experienced these failures less often because of a combination of functional, interpersonal, and stakeholder engagement mechanisms, which appear to complement one another. Integration perspectives, including both people-oriented and systems-oriented mindsets, appear to play a role in generating these integration dynamics. CONCLUSION: Delivering integrated care depends on a PO's ability to limit integration failures, keeping provider attention focused on patients. Building on the attention-based view, we present a framework suggesting that this ability is a function of both integration perspectives and integration engagement mechanisms. PRACTICE IMPLICATIONS: POs interested in delivering more integrated care should employ a variety of complementary integration engagement mechanisms and facilitate these efforts by nurturing both people-oriented and system-oriented mindsets among PO decision-makers.
Subject(s)
Delivery of Health Care, Integrated , Physicians , HumansABSTRACT
INTRODUCTION: Oral squamous cell carcinoma (OSCC) in the young (<50 years), without known carcinogenic risk factors, is on the rise globally. Whole genome duplication (WGD) has been shown to occur at higher rates in cancers without an identifiable carcinogenic agent. We aimed to evaluate the prevalence of WGD in a cohort of OSCC patients under the age of 50 years. METHODS: Whole genome sequencing (WGS) was performed on 28 OSCC patients from the Sydney Head and Neck Cancer Institute (SHNCI) biobank. An additional nine cases were obtained from The Cancer Genome Atlas (TCGA). RESULTS: WGD was seen in 27 of 37 (73%) cases. Non-synonymous, somatic TP53 mutations occurred in 25 of 27 (93%) cases of WGD and were predicted to precede WGD in 21 (77%). WGD was significantly associated with larger tumor size (p = 0.01) and was frequent in patients with recurrences (87%, p = 0.36). Overall survival was significantly worse in those with WGD (p = 0.05). CONCLUSIONS: Our data, based on one of the largest WGS datasets of young patients with OSCC, demonstrates a high frequency of WGD and its association with adverse pathologic characteristics and clinical outcomes. TP53 mutations also preceded WGD, as has been described in other tumors without a clear mutagenic driver.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Carcinoma, Squamous Cell/genetics , Gene Duplication , Head and Neck Neoplasms/genetics , Humans , Middle Aged , Mouth Neoplasms/genetics , Squamous Cell Carcinoma of Head and Neck/geneticsABSTRACT
INTRODUCTION: Centralisation of head and neck surgical services means that patients in regional and remote Australia need to travel long distances for treatment and follow-up, imparting a significant financial burden on patients and the health system. OBJECTIVE: To estimate costs of travel to local outreach clinics and determine potential cost savings to patients and the health system by avoiding patient travel to major cities for head and neck surgical care. DESIGN: Retrospective audit of three head and neck surgery outreach clinics in New South Wales, Australia over 4 years (2017-2020). Direct costs of travel from a patient's residence to their local outreach clinic were estimated. Costs of travel and accommodation to Sydney for an appointment were calculated for different travel modes. Estimated reimbursements for travel through government support schemes were calculated based on published rates. FINDINGS: Some 657 patients attended the three clinics, accounting for 1981 appointments. Depending on mode of travel, the estimated median cost of return travel (including accommodation) to Sydney was $379 to $739 per patient per trip and the median government reimbursement ranged from $182 to $279 per trip. In comparison, the cost of return travel by car to local outreach clinics ranged from $28 to $163 per appointment. Outreach clinics were estimated to save patients a median of $285 per trip and avoided government reimbursements of $215 per trip. DISCUSSION: Despite uptake in telehealth, outreach medical services remain an important asset for people living in regional areas to address inequities in access. However, the cost benefits are likely to be underestimated as our approach did not account for indirect costs associated with travel. CONCLUSION: Outreach head and neck surgical services located in regional areas can reduce the financial burden on both patients and the healthcare system. Greater investment in outreach clinics could ensure sustainability of services to promote equitable access to specialised surgical services.
Subject(s)
Health Services Accessibility , Travel , Humans , New South Wales , Cost Savings , Retrospective Studies , AustraliaABSTRACT
BACKGROUND: pT3/4 head and neck cutaneous squamous cell carcinomas (HNcSCCs) are associated with poor outcomes, including local recurrence, metastasis and death. Whilst surgery remains the standard treatment for advanced HNcSCC, novel systemic therapies, such as immunotherapy, are being used earlier in the treatment paradigm. It is imperative that the clinical outcomes of surgery are clearly described so that conventional and emerging treatment modalities can be better integrated and sequenced in the management of pT3/4 HNcSCC. METHODS: Patients with confirmed pT3/4 HNcSCC undergoing curative surgical resection between 2014-2020 were identified retrospectively from a prospectively maintained research database. The primary outcomes of interest were locoregional control (LRC), disease-specific survival (DSS), and overall survival (OS). The secondary outcome was surgical complication rate. RESULTS: A total of 104 patients (median age 74, range 41-94 years) were included, 90% of which had pT3 tumors; 36.5% received adjuvant radiotherapy. Median follow-up was 24.3 (range 1.0-84.3) months. LRC at 5 years was 62.0%, DSS at 5 years was 83.7%, and OS at 5 years was 71.9%. Median time to recurrence was 8.4 months. LRC was reduced in the presence of margin involvement and previous treatment (radiotherapy/surgery). The major surgical complication rate was 9.6%. CONCLUSIONS: More than 60% of patients treated surgically for pT3/4 head and neck cSCC were alive and free of disease at 5 years posttreatment. High-risk features such as margin involvement and having had previous treatment (radiotherapy/surgery) should be used to guide adjuvant therapy.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Skin Neoplasms , Adult , Aged , Aged, 80 and over , Benchmarking , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Disease-Free Survival , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/surgery , Humans , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Retrospective Studies , Skin Neoplasms/pathology , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/surgeryABSTRACT
BACKGROUND: The order of significance of clinicopathologic characteristics for the prognosis of patients with regional metastases from head and neck cutaneous squamous cell carcinoma (HNcSCC) is not well characterized. This study aimed to understand the impact of the known characteristics, including the presence of immunosuppression, number of deposits, largest deposit size, location and laterality of deposits, and presence of extranodal extension (ENE) on overall survival (OS) and disease-specific survival (DSS). METHODS: A retrospective study of 366 patients treated with curative intent for HNcSCC with regional metastatic disease was undertaken using recursive partitioning analysis (RPA). RESULTS: Using RPA modeling, the study determined that number of metastatic deposits carried the highest impact for both OS and DSS, followed by largest deposit size. The presence of ENE and immunosuppression was less significant. CONCLUSIONS: The results from this study provide new evidence for identifying and stratifying high-risk patients with metastatic HNcSCC. This information will be valuable in determining future HNcSCC staging systems.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Skin Neoplasms , Carcinoma, Squamous Cell/pathology , Extranodal Extension , Head and Neck Neoplasms/therapy , Humans , Lymphatic Metastasis , Retrospective Studies , Skin Neoplasms/pathology , Squamous Cell Carcinoma of Head and NeckABSTRACT
OBJECTIVE: The objective of this study to explore experiences of patients and carers of the pathway to diagnosis and treatment of head and neck cancer (HNC), focusing on differences based on remoteness of residence. METHODS: Patients ≥6 months post-treatment completion, and their carers, were recruited. Semi-structured interviews, guided by the Model of Pathways to Treatment as the theoretical framework, were conducted to examine pathways to treatment of HNC and facilitators and barriers to early diagnosis and treatment. Thematic analysis with an iterative and data-driven approach was used to identify themes. RESULTS: A total of 39 patients and 17 carers participated in the interviews. Facilitators of timely diagnosis and treatment included a sense of urgency from health care professionals (HCPs), advocacy by the HCP or carers, and leveraging social capital. Distance to services, financial costs, and a perceived lack of emotional investment by HCPs arose as barriers to timely diagnosis and treatment. Participants were often able to rationalise that not all delays were negative, depending causes and expected impact on cancer management. CONCLUSION: The findings highlight the complex nature of factors facilitating and impeding early HNC diagnosis and treatment that may be targeted in interventions to support patients and meet important benchmarks for high-quality cancer care.
Subject(s)
Caregivers , Head and Neck Neoplasms , Humans , Caregivers/psychology , Early Detection of Cancer , Health Personnel/psychology , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/therapy , Qualitative ResearchABSTRACT
INTRODUCTION: General practitioners (GPs) play a crucial role in cancer care and GPs are often the first doctor that patients with symptoms suggestive of cancer will encounter. Head and neck cancer (HNC) is a relatively uncommon presentation in primary care, and evidence suggests that times to diagnosis and treatment of HNC vary based on geographical location of patients. This may be due to barriers to referral faced by regional or rural GPs as compared to those in metropolitan cities in Australia. OBJECTIVE: To investigate the effect of geographical location of GPs on management of patients with symptoms suggestive of HNC. DESIGN: This was a descriptive, analytical, cross-sectional survey. Surveys were sent to GPs at practices in two primary health care networks in New South Wales, Australia (Mid North Coast Primary Healthcare Network and the Central and Eastern Sydney Primary Healthcare Network) between February and May 2020. Main outcome measures were perceived time from referral to specialist appointment, factors affecting timeliness of patient help-seeking, and awareness and use of clinical guidelines. FINDINGS: A total of 1803 GPs were sampled, of which 196 responded (45 regional GPs and 151 metropolitan GPs). Less than half (48%) of regional GPs reported patients could expect to be seen by a specialist within 2 weeks of referral, compared to 70% of metropolitan GPs (p = 0.001). Most metropolitan GPs stated they would refer a patient with suspected HNC to a surgeon subspecialising in HNC. Regional GPs were split between ear, nose, and throat (ENT) and general surgeons. Availability of services was the most common factor influencing referral practices for regional GPs, whereas for metropolitan GPs, this was the patient's symptoms. Awareness of government resources for cancer referrals was generally low. DISCUSSION: Regional GPs report patients with HNC are less likely to be seen by a specialist within optimal time frames compared to metropolitan GPs. Respondents reported different barriers to early referral of patients with suspected HNC, with regional GPs more often citing system-level factors while metropolitan GPs more often cited patient-level factors. CONCLUSION: Evaluating service provision and uptake with respect to community need, and addressing of barriers to implementation, may minimise unwarranted clinical variation.
Subject(s)
General Practitioners , Neoplasms , Australia , Cross-Sectional Studies , Humans , Referral and Consultation , Surveys and QuestionnairesABSTRACT
BACKGROUND: The vermilion lip is a unique anatomical junction between cutaneous and mucosal surfaces. Squamous cell carcinoma (SCC) of the vermilion lip (vlSCC) was previously classified as oral SCC (oSCC) under the American Joint Committee on Cancer (AJCC) 7th edition (AJCC7), but has been recategorized as a cutaneous SCC of the head and neck (HNcSCC) in the AJCC 8th edition (AJCC8). We investigated the locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) for the various pathological T categories and disease stages of vlSCC as per AJCC8. METHODS: We performed a retrospective cohort study of 297 patients diagnosed with vlSCC between January 2004 and February 2019. For this study, vlSCC cases were staged according to both AJCC7 and AJCC8. Kaplan-Meier survival curves and Cox regression models were used to analyze differences in LRC, DFS, and OS between each pT category and disease stage, and log-rank tests were performed for subgroup analysis. RESULTS: Restaging of vlSCC using the AJCC8 resulted in 19% of patients being upstaged to pT3, and 16% being upstaged to stage III. No patients were downstaged in pT stage or overall stage. CONCLUSIONS: Our study shows that when the AJCC8 HNcSCC staging system is applied to vlSCC, there are important aberrations leading to unwarranted upstaging of pT1 and redundancy of pT2. Understanding of these limitations are important in considering treatment escalation.
Subject(s)
Carcinoma, Squamous Cell , Lip , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Humans , Lip/pathology , Neoplasm Staging , Prognosis , Retrospective Studies , United StatesABSTRACT
BACKGROUND AND OBJECTIVES: We performed a critical analysis of the 8th edition American Joint Committee on Cancer (AJCC) staging for head and neck cutaneous squamous cell carcinoma (HNcSCC) with nodal metastases and compared the performance to the N1S3 and ITEM systems. METHODS: Multicenter study of 990 patients with metastatic HNcSCC treated with curative intent. The end points of interest were disease-specific (DSS) and overall survival (OS). Model fit was evaluated using Harrell's Concordance Index (C-index), proportion of variation explained (PVE), Akaike information criterion, and Bayesian information criterion. RESULTS: N1S3 and ITEM demonstrated good distribution into risk categories in contrast to the AJCC system, which classified the majority (90.6%) of patients as N2-3 and Stage IV due to the high rate of extranodal extension. The N2c and N3a categories appeared redundant. There was considerable discordance between systems in risk allocation on an individual patient basis. N1S3 was the best performed (DSS: C-index 0.62, PVE 10.9%; OS: C-index 0.59, PVE 4.5%), albeit with relatively poor predictive value. CONCLUSIONS: The AJCC N category and tumor node metastasis stage have poor patient distribution and predictive performance in HNcSCC. The AJCC stage, N1S3, and ITEM score all provide limited prognostic information based on objective measures highlighting the need to develop a staging system specific to HNcSCC.
Subject(s)
Head and Neck Neoplasms/pathology , Skin Neoplasms/pathology , Squamous Cell Carcinoma of Head and Neck/pathology , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Survival RateABSTRACT
BACKGROUND: Health care scholars have recognized the important role leaders play in the improvement of health care delivery systems, yet few have explored the kind of leaders who make a difference or the conditions under which certain health care executives thrive. Recent work in the hospital industry suggests that the role of chief executive officer (CEO) gender may be particularly salient in the context of patient experience (Galstian, Hearld, O'Connor, & Borkowski, 2018). PURPOSE: In this article, we bring an explicit theoretical and empirical lens to the issue of CEO gender in the context of patient experience. Our framework provides an explanation of both why (differences between men and women in their tendency for relational orientation) and under what circumstances (the degree of complexity in the executive job environment) CEO gender is most influential. METHODOLOGY/APPROACH: We test these relationships using data on patient experience in 391 nonrural U.S. hospitals between 2007 and 2011. Our study relies on both archival (e.g., Hospital Consumer Assessment of Healthcare Providers and Systems survey) and collected (e.g., CEO characteristics) data. Fixed-effects regression models are used to estimate the relationship between CEO gender and the interpersonal care experience. RESULTS: We find evidence that female CEOs improve the interpersonal care experience faster than male CEOs, particularly in the most complex executive job environments, that is, in the most populous urban environments, and in the largest hospital facilities. CONCLUSION: Our results not only support the notion that executives tend to rely on personal values and preferences but also that women have an apparent propensity for transforming health care organizations in the direction of patient centeredness, particularly in the most demanding circumstances. PRACTICE IMPLICATIONS: Hospital boards seeking to improve the patient experience should give careful attention to promoting women to the role of CEO and consider how their own policies may be constraining both the promotion of female executives and the creation of more patient-centered health care organizations.
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Salivary duct carcinoma (SDCa) is a rare cancer with high rate of metastases and poor survival despite aggressive multimodality treatment. This study analyzes the genetic changes in SDCa, their impact on cancer pathways, and evaluates whether molecular patterns can identify subgroups with distinct clinical characteristics and outcome. Clinicopathologic details and tissue samples from 66 patients (48 males, 18 females) treated between 1995 and 2018 were obtained from multiple institutions. Androgen receptor (AR) was assessed by immunohistochemistry, and the Illumina TruSight 170 gene panel was used for DNA sequencing. Male gender, lympho-vascular invasion, lymph node metastasis, and smoking were significant predictors of disease-free survival. AR was present in 79%. Frequently encountered alterations were mutations in TP53 (51%), PIK3CA (32%) and HRAS (22%), as well as amplifications of CDK4/6 (22%), ERBB2 (21%), MYC (16%), and deletions of CDKN2A (13%). TP53 mutation and MYC amplifications were associated with decreased disease-free survival. Analysis of cancer pathways revealed that the PI3K pathway was most commonly affected. Alterations in the cell cycle pathway were associated with impaired disease-free survival (HR 2.6, P = 0.038). Three subgroups based on AR and ERBB2 status were identified, which featured distinct molecular patterns and outcome. Among AR positive SDCa, HRAS mutations were restricted to AR positive tumors without ERBB2 amplification and HRAS mutations featured high co-occurrence with PIK3CA alterations, which seems specific to SDCa. AR negative SDCa were associated with poor disease-free survival in multivariate analysis (HR 4.5, P = 0.010) and none of these tumors exhibited ERBB2 amplification or HRAS mutations. AR and ERBB2 status in SDCa thus classifies tumors with distinct molecular profiles relevant to future targeted therapy. Furthermore, clinical factors such as smoking and molecular features such as MYC amplification may serve as markers of poor prognosis of SDCa.
Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Ductal/genetics , Salivary Gland Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , PrognosisABSTRACT
BACKGROUND: The treatment of advanced cutaneous head and neck cutaneous squamous cell carcinomas (HNcSCC) results in significant morbidity. Recently, immune checkpoint inhibitor treatment has been approved for DNA mismatch repair (MMR) deficient patients in a histology-agnostic manner. This study aims to evaluate the incidence of MMR deficiency in advanced HNcSCC and its association with clinicopathologic factors. METHODS: The cohort included 176 consecutive HNcSCC cases treated with curative intent. Immunohistochemistry for MMR proteins (hMLH1, hMSH2, hMSH6, and hPMS2) was performed. Clinicopathological and survival data was collected prospectively. RESULTS: The incidence of MMR protein deficiency was 9.1%. There was no association between age, incidence of metachronous malignancies, clinicopathological factors, or survival outcomes. CONCLUSION: A higher incidence of MMR deficiency was observed in this cohort of advanced HNcSCC. The lack of association with young age at onset or increased incidence of metachronous malignancies suggests that MMR deficiency is likely to be sporadic in HNcSCC.
Subject(s)
Biomarkers, Tumor/metabolism , Brain Neoplasms/epidemiology , Colorectal Neoplasms/epidemiology , DNA Mismatch Repair , DNA Repair Enzymes/metabolism , Neoplastic Syndromes, Hereditary/epidemiology , Skin Neoplasms/complications , Squamous Cell Carcinoma of Head and Neck/complications , Aged , Australia/epidemiology , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Female , Follow-Up Studies , Humans , Incidence , Male , Neoplastic Syndromes, Hereditary/metabolism , Neoplastic Syndromes, Hereditary/pathology , Prognosis , Prospective Studies , Retrospective Studies , Survival RateABSTRACT
BACKGROUND: Regional nodal metastases from cutaneous squamous cell carcinoma (cSCC) is strongly associated with a poor prognosis, but these metastases are difficult to predict clinically. Sentinel node biopsy (SNB) has been used for a wide range of malignancies to assess for regional nodal metastasis, but is not widely used for cSCC. METHODS: Patients presenting with high-risk cSCC of the head and neck with clinically N0 necks were offered SNB at the time of primary cSCC excision or secondary wide local excision. Patients with positive sentinel nodes were offered completion lymph node dissection, and all the patients were followed up at regular intervals for up to 5 years. RESULTS: In this study, 105 lesions underwent SNB, and 10 sentinel nodes (9.5%) were positive. In an additional five patients, regional recurrence developed after a negative sentinel node, with a total subclinical nodal metastasis rate of 14.3%. Nodal metastases were significantly associated with reduced disease-specific survival. The significant predictors of metastasis were four or more high-risk features or tumors with a concurrent invasion deeper than 5 mm and PNI. CONCLUSION: For high-risk cSCC, SNB is a safe and feasible staging technique. The total number of high risk features and certain combinations of high-risk features predicted metastasis better than individual high-risk features.
Subject(s)
Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/surgery , Sentinel Lymph Node Biopsy , Adult , Aged , Aged, 80 and over , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Prognosis , Prospective StudiesABSTRACT
BACKGROUND: Scholars have noted a disconnect between the level at which structure is typically examined (the organization) and the level at which the relevant coordination takes place (service delivery). Accordingly, our understanding of the role structure plays in care coordination is limited. PURPOSE: In this article, we explore service line structure, with an aim of advancing our understanding of the role service line structure plays in producing coordinated, patient-centered care. We do so by giving special attention to the cognitive roots of patient-centeredness. METHODOLOGY/APPROACH: Our exploratory study relied on comparative case studies of the breast cancer service lines in three health systems. Nonprobability discriminative snowball sampling was used to identify the final sample of key informants. We employed a grounded approach to analyzing and interpreting the data. RESULTS: We found substantial variation across the three service lines in terms of their structure. We also found corresponding variation across the three case sites in terms of where informant attention was primarily focused in the process of coordinating care. Drawing on the attention-based view of the firm, our results draw a clear connection between structural characteristics and the dominant focus of attention (operational tactics, provider roles and relationships, or patient needs and engagement) in health care service lines. CONCLUSION: Our exploratory results suggest that service line structures influence attention in two ways: (a) by regulating the type and intensity of the problems facing service line participants and (b) by encouraging (or discouraging) a shared purpose around patient needs. PRACTICE IMPLICATIONS: Patient-centered attention-a precursor to coordinated, patient-centered care-depends on the internal choices organizations make around service line structure. Moreover, a key task for organizational and service line leaders is to structure service lines to create a context that minimizes distractions and enables care providers to focus their attention on the needs of their patients.