In a world in which charitable activities are increasingly crossing national borders, the Australian Government has had to reconsider its regulation of cross-border charity. Recent developments have ...resulted in a number of proposed regulatory reforms and a new tax ruling directly impacting Australian charities operating overseas. This article evaluates the government's existing and proposed measures to regulate Australian cross-border charity in a changing global landscape. In doing so, it examines whether the promised reforms will enable the government to fulfil its policy goals of reducing the administrative complexity for Australian charities operating overseas and safeguarding their charitable assets, while ensuring that public trust and confidence in these charities is preserved.
In a world in which charitable activities are increasingly crossing national borders, the Australian Government has had to reconsider its regulation of cross-border charity. Recent developments have ...resulted in a number of proposed regulatory reforms and a new tax ruling directly impacting Australian charities operating overseas. This article evaluates the government's existing and proposed measures to regulate Australian cross-border charity in a changing global landscape. In doing so, it examines whether the promised reforms will enable the government to fulfil its policy goals of reducing the administrative complexity for Australian charities operating overseas and safeguarding their charitable assets, while ensuring that public trust and confidence in these charities is preserved.
For many decades, surgery has been the primary treatment for malignant submandibular gland neoplasms. Nonetheless, due to the heterogeneity and rarity of submandibular gland malignant tumors and the ...high frequency of chronic benign processes in this region, management can be complex. Preoperative investigations, such as fine-needle aspiration and imaging, are critical to achieve the correct diagnosis so that appropriate surgery can be planned. In general, for malignant submandibular gland neoplasms, the minimal treatment necessary is excision of the submandibular gland with level I lymph node dissection. Salivary gland cancer in the submandibular gland is generally more aggressive than the same histologic type in the parotid gland. Neck dissection may be required and primarily depends on the stage and histological grade. Adjuvant therapy most frequently consists of radiation and can improve overall survival. Some factors that influence prognosis after surgical treatment include the histologic grade, stage at presentation, and positive surgical margins.
e15034 Background: Circulating tumor DNA (ctDNA) has emerged as a potential noninvasive biomarker to assess tumor burden throughout cancer treatment and to aid in clinical decision-making. However, ...data on the use of ctDNA in cutaneous squamous cell carcinoma (cSCC) is currently lacking. In this study, we report our first experience with ctDNA in patients with cSCC. Methods: In this IRB-approved study at a tertiary care center, an initial cohort of patients with intermediate to high-risk cSCC had tissue and plasma sent for ctDNA analysis using Natera®’s proprietary bioinformatics pipeline. This cohort included 21 patients treated from 2023 to the present. Initial tissue samples were obtained through biopsy (i.e., excisional, punch, or shave), Mohs surgery, or surgical resection. Some patients had additional plasma sample(s) drawn later during or after the treatment course. Patients either received a “positive,” “positive below analytical range,” or “negative” result or had ‘insufficient sample’ to receive a result based on Natera®’s analysis. All patients were treated curatively with surgical resection with or without adjuvant radiation as per the standard of care. The assessment of gross disease was determined based on whether the patient had disease present on imaging or physical exam at the time of the plasma draw. A comparison of ctDNA results and the presence of gross disease was done using Fisher’s exact test. Results: Of the samples submitted for Natera® ctDNA analysis, 18/21 had sufficient tissue for analysis of tumor DNA. All 3 tumors with insufficient tissue were from biopsies (6/9 sufficient), while 12/12 of those from Mohs or surgical resection had sufficient tissue. The average tumor volume in these patients with insufficient samples for tumor analysis was relatively low (0.35 cm 3 ) compared to those that resulted (17-30 cm 3 ). 7/9 (78%) patients with gross disease had a positive ctDNA result, which was significantly greater than those with no gross disease (1/9 patients, 11%) (p = 0.004). Three patients in our cohort with an initially positive ctDNA result had multiple plasma draws, with all having a later draw demonstrating a negative ctDNA result after having surgery and/or radiation. Conclusions: Circulating tumor DNA is a reliable marker for patients with cSCC with a high tumor burden and is feasible in those with adequate tissue. However, in patients where it is only possible to obtain a small volume of tumor tissue and/or low tumor burden, ctDNA may be a less reliable biomarker. Table: see text
9585 Background: Neoadjuvant immunotherapy is a potential curative approach to patients with locally advanced cutaneous squamous cell carcinoma (cSCC) that offers an attractive alternative to ...traditional, often morbid surgery and/or radiation. In this study, we report our initial institutional experience treating patients with primary immunotherapy monotherapy (PRIMO) and reserving surgery or radiation for progression only. Methods: Patients with primary or recurrent locally advanced cSCC (AJCC 8 T3-4 or node positive or in-transit metastases) in whom surgical resection and/or definitive radiation were deemed excessively morbid or futile and were treated with PRIMO were included in an IRB-approved database. Patients were treated with IV cemiplimab (350mg q 3week) or pembrolizumab (200mg q3week or 400 q6week). Complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) was scored according to iRECIST criteria. Kaplan Meier analysis was used to estimate overall survival (OS) and progression free survival (PFS). Univariate analysis (UVA) for PD was performed using Chi square for categorical variables and Kruskal-Wallis for continuous variables. Results: This study included 36 patients treated between 2017-2023, with a median age of 80 (61-96), and a median follow up of 13.5 months (8-20.5). Most patients had lesions on the head and neck (32; 88.9%), recurrent disease (26; 72.2%), and T3/4N0 disease (20; 55.6%), while 18 patients (50.0%) had nodal disease or in-transit metastases. Cemiplimab was used in 31 patients (86.1%) while pembrolizumab was used for 5 patients (13.9%). Twelve patients (33.3%) stopped PRIMO due to an immune-related adverse event (irAE). 1 and 2yr OS and 1 and 2yr PFS were 76%, 64%, 72% and 51%, respectively. Best initial response to PRIMO was a CR in 15 (41.7%), PR in 14 (38.9%), SD in 3 (8.3%) and PD in 4 (11.1%) patients. All 3 lesions (100%) with SD and 3/14 lesions (21.4%) with PR ultimately progressed with a median duration of response of only 3 months (2.0-6.8), while all 15 lesions (100%) with a CR and 11/14 lesions with a PR (78.5%) remain controlled at last follow up with a median duration of response of 15.5 months (8.8 – 23.3) (p<0.001). The median duration of months of ongoing response after the completion of PRIMO was 11 (0-57). The median number of treatment cycles was 14 (2-36) in all patients, and 16 (2-36) in the 26 patients that did not progress. The only variable significantly associated with PD on UVA was the lack of irAE; 10/26 (38.5%) patients who did not have an irAE experienced PD, while 0/12 patients (0%) who had an irAE experienced PD (p=0.035). Conclusions: The use of PRIMO for locally advanced cSCC produces impressive response rates that appear durable without any additional therapy. This attractive alternative to the emerging neoadjuvant paradigm deserves prospective validation with longer term follow up.
•Reflex cough airflows are reduced vs to volitional cough airflows.•Cough airflows are reduced for aspirators vs non-aspirators.•Cough airflows are reduced for those recently s/p treatment vs long ...term survivors.
The aim of this study was to investigate differences in reflexive and volitional cough airflows in advanced stage head and neck cancer survivors as it relates to aspiration status and time since treatment. The hypothesis is that those who aspirate several years after treatment completion would demonstrate reduced airflows for all cough parameters compared to those recently status post treatment completion given the known progressive deterioration associated with radiotherapy.
Demographic and airflow data during both reflexive and volitional cough tasks and aspiration status as determined during fiberoptic endoscopic evaluation of swallow function were collected from 33 Head and Neck Cancer (HNC) survivors.
Omnibus MANOVA for dependent airflow variables and independent variables aspiration status, time since treatment and cough type (reflex or volitional) was significant (F(3,1) = 184, p < 0.000) indicating that peak expiratory flow rates (PEFR) were reduced under reflex (mean PEFR 1.88 SD 0.7) versus volitional (mean PEFR 2.3, SD 0.7) cough types; reduced for aspirators versus non-aspirators (F(2,1) = 4.1, p = 0.04) and reduced for those in the subacute versus chronic phase status post Intensity Modulated Radiotherapy (IMRT) (F(2,1) = 10.05, p = 0.002).
Findings of reduced reflexive compared to volitional cough airflows in head and neck cancer survivors are consistent with those from both healthy and other diseased populations. Additional findings that aspirators demonstrate reduced cough airflows compared to non-aspirators supports the hypothesis. Surprisingly, those recently status post treatment completion show worse cough airflows compared to those remotely status post treatment completion.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objectives/Hypothesis
Head and neck cancer pain is a prevalent problem, and the current opioid crisis has highlighted concerns raised in chronic pain management. This study assessed the ...characteristics of opioid use in patients undergoing treatment for oropharynx cancer and identified risk factors associated with chronic opioid use.
Study Design
Retrospective cohort study.
Methods
A study was conducted of 198 eligible patients who underwent radiotherapy as part of their treatment for oropharynx cancer at a single institution from 2012 to 2017. p16/human papillomavirus (HPV) status was determined by pathology report review. Opioid use was recorded. Statistical analysis was performed to assess risk factors for chronic opioid use and effect on overall survival.
Results
The average age was 62 years, and the mean follow‐up was 38 months. Eighty‐three percent of patients had stage III/IV disease, and 73% received chemoradiotherapy. Sixty‐nine percent were HPV/p16 positive. Fifty‐seven (29%) patients had preexisting chronic pain conditions. Chronic opioid use was observed in 53% of the patients. Age ≤ 62 years (P < .0001), history of depression (P = .0356), p16 negative status (P = .0097), opioid use at pretreatment visit (P = .0021), and presence of a preexisting chronic pain condition at time of diagnosis (P = .0181) were associated with chronic opioid use using univariate analysis. On multivariate analysis, T stage and anxiety/depression were associated with chronic opioid use. Overall survival was worse for patients who had chronic opioid use, but was not significant when recurrence was taken into consideration.
Conclusions
More than 50% of the patients treated for oropharynx squamous cell carcinoma in this cohort were chronic opioid users after treatment. Identifying patients at greatest risk for chronic opioid use prior to treatment may help with long‐term pain management in this patient population.
Level of Evidence
4
Laryngoscope, 129:2087–2093, 2019
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objectives/Hypothesis:
To evaluate the population characteristics of mucosal melanoma of the nasal cavity and paranasal sinuses and determine the impact of the new staging classification.
Study ...Design:
Analysis of a national database.
Methods:
Patients were identified from the Surveillance, Epidemiology, and End Results tumor registry data with mucosal melanoma of the nasal cavity and paranasal sinuses between 2000 and 2007. Tumors were classified using the American Joint Committee on Cancer (AJCC) 6th edition site‐specific staging as well as 7th edition staging for head and neck mucosal melanoma (HNMM). Incidence rates and descriptive statistics were calculated, and multivariate analysis was performed to examine the impact of demographic factors and staging on survival.
Results:
A total of 304 patients were identified. The incidence rate was 0.05 per 100,000. Fifty‐six percent were female, 92% were >50 years old, and more than 90% were Caucasian; 81.6% of patients were treated with surgery, and 38.5% of patients received postoperative radiation. Overall, the 5‐year survival rate was 24.2%. Significant differences in survival were observed for surgery with radiation (P = .005) and surgery alone (P = .04) compared with radiation alone. TNM staging using the AJCC 6th and 7th edition classification schemes yielded similar survival curves. However, the new classification for HNMM allows for better delineation of stage IV disease, revealing slightly improved survival for stage IVA disease.
Conclusions:
HNMM is a rare disease with a poor prognosis. Surgery remains the treatment of choice, with some role for adjuvant therapy. The new staging classification for HNMM appears to more efficiently stage this disease. Demographics and therapeutic findings are discussed.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Objectives: Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide with a poor prognosis of ~40% at 5 years for HPV-negative disease. Recently, immune ...checkpoint inhibitors (specifically, anti-PD-1 checkpoint inhibitors that block the PD-L1/PD-1 immunosuppressive axis) have been approved as a treatment for patients with recurrent/metastatic HNSCC. However, most patients (>80%) fail to respond to checkpoint inhibitors. PD-L1 expression on tumors plays an important role in immune evasion and can also influence response to checkpoint inhibitors. Tumor PD-L1 expression has been shown to correlate with checkpoint response. Factors that might affect PDL1 expression in HNSCC remain unclear. In this study, we explored the effect of periodontal bacteria, which has been associated with oral cancer, on PD-L1 expression in oral cancer cells.
Materials and Methods: 303 HNSCC were compared to 37 adjacent control tissues in the TCGA mRNA expression database (RNASeq V2); the analysis was done based on tumor types. RT-PCR and flow cytometry were used to measure the base line expression of PD-L1 in seven head and neck cancer cell lines and human oral tissues. OQ01, an oral cancer cell line, was infected with four periodontal bacteria (Tanneralla forsynthia, Treponema denticola, Porphyromonas gingivalis, and Fusobacterium nucleatum). OQ01 and RPMI2650 cells were infected with two different strains of Fusobacteria (F. periodonticum, F. vincentii). The relative changes in expression of PLD1 was measured using RT-PCR in cell lysate after RNA isolation. PD-L1 protein level on the cell surface was measured using flow cytometry.
Results: TCGA data analysis revealed that PDL1 was significantly (P< 0.0005) elevated in total cancer tissues compared to total controls. In the same data analysis, PDL1 expression was significantly (P< 0.05) elevated in oral cavity tumor compared to normal control. Expression of PD-L1 was variable among head and neck cancer patients and cell lines. Both F. nucleatum and P. gingivalis were able to enhance PD-L1 expression in OQ01 cells (10 and 15 fold, respectively). Two strains of Fusobacteria tested (F. periodonticum, F. vincentii) were also able to induce PD-L1 both at the mRNA (P< 0.005 and P< 0.05 respectively) and protein level in OQ01 and RPMI 2650 cells. Interestingly, the same strains of Fusobacteria enhanced MYC expression in OQ01 and RPMI 2650 cells. As a transcription factor MYC has been reported to regulate PDL1 transcription. These data along with our results suggest that Fusobacterial upregulation of PD-L1 expression might be through MYC enhanced expression.
Conclusions: This study revealed that Fusobacteria enhance PD-L1 expression on HNSCC cancer cell lines, possibly through upregulation of MYC. This may have implications on cancer cell immune evasion and checkpoint inhibitor treatment response.
Note: This abstract was not presented at the conference.
Citation Format: Amani Harrandah, Rekha Rani Grag, Yuk Pheel Park, Sasanka S. Chukkapalli, Nikhita Yadlapalli, Edward K. L. Chan, Natalie Silver. Fusobacteria upregulates PD-L1 in head and neck cancer cell lines: Potential mechanism for immune evasion abstract. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A10.
PDF
