Understanding patient barriers and facilitators to uptake of lung screening using low dose computed tomography: a mixed methods scoping review of the current literature.

BACKGROUND: Targeted lung cancer screening is effective in reducing mortality by upwards of twenty percent. However, screening is not universally available and uptake is variable and socially patterned. Understanding screening behaviour is integral to designing a service that serves its population and promotes equitable uptake. We sought to review the literature to identify barriers and facilitators to screening to inform the development of a pilot lung screening study in Scotland. METHODS: We used Arksey and O'Malley's scoping review methodology and PRISMA-ScR framework to identify relevant literature to meet the study aims. Qualitative, quantitative and mixed methods primary studies published between January 2000 and May 2021 were identified and reviewed by two reviewers for inclusion, using a list of search terms developed by the study team and adapted for chosen databases. RESULTS: Twenty-one articles met the final inclusion criteria. Articles were published between 2003 and 2021 and came from high income countries. Following data extraction and synthesis, findings were organised into four categories: Awareness of lung screening, Enthusiasm for lung screening, Barriers to lung screening, and Facilitators or ways of promoting uptake of lung screening. Awareness of lung screening was low while enthusiasm was high. Barriers to screening included fear of a cancer diagnosis, low perceived risk of lung cancer as well as practical barriers of cost, travel and time off work. Being health conscious, provider endorsement and seeking reassurance were all identified as facilitators of screening participation. CONCLUSIONS: Understanding patient reported barriers and facilitators to lung screening can help inform the implementation of future lung screening pilots and national lung screening programmes.

Optimizing the implementation of lung cancer screening in Scotland: Focus group participant perspectives in the LUNGSCOT study.

INTRODUCTION: Targeted lung cancer screening is effective in reducing lung cancer and all-cause mortality according to major trials in the United Kingdom and Europe. However, the best ways of implementing screening in local communities requires an understanding of the population the programme will serve. We undertook a study to explore the views of those potentially eligible for, and to identify potential barriers and facilitators to taking part in, lung screening, to inform the development of a feasibility study. METHODS: Men and women aged 45-70, living in urban and rural Scotland, and either self-reported people who smoke or who recently quit, were invited to take part in the study via research agency Taylor McKenzie. Eleven men and 14 women took part in three virtual focus groups exploring their views on lung screening. Focus group transcripts were transcribed and analysed using thematic analysis, assisted by QSR NVivo. FINDINGS: Three overarching themes were identified: (1) Knowledge, awareness and acceptability of lung screening, (2) Barriers and facilitators to screening and (3) Promoting screening and implementation ideas. Participants were largely supportive of lung screening in principle and described the importance of the early detection of cancer. Emotional and psychological concerns as well as system-level and practical issues were discussed as posing barriers and facilitators to lung screening. CONCLUSIONS: Understanding the views of people potentially eligible for a lung health check can usefully inform the development of a further study to test the feasibility and acceptability of lung screening in Scotland. PATIENT OR PUBLIC CONTRIBUTION: The LUNGSCOT study has convened a patient advisory group to advise on all aspects of study development and implementation. Patient representatives commented on the focus group study design, study materials and ethics application, and two representatives read the focus group transcripts.

Resilience and ongoing quality care for cancer clinical trials during COVID-19: Experience from a tertiary hospital in Australia.

BACKGROUND: The COVID-19 pandemic has forced rapid system-wide changes to be implemented within cancer care at an alarming pace. Clinical trials are a key element of comprehensive cancer care. Ensuring the continuing safe conduct of cancer clinical trials in the context of a pandemic is challenging. METHODS: We aimed to describe the COVID-19 pandemic response of a Cancer Care Clinical Research Unit (CRU) of a tertiary hospital in Queensland, Australia. We used a mixed methods approach for this case study. Emailed directives from CRU managers to all CRU staff sharing were qualitatively analysed and mapped against our unit activities over longitudinal time points. Data from patient recruitment and protocol deviations were analysed using descriptive statistics. RESULTS: Mapping activity from 11 March to 30 September 2020 revealed rapid change during the first 2 weeks. Four key strategies to accommodate change were identified: supporting patients and families, introduction of telehealth, accessing investigational product, and social distancing. Early in the pandemic we recognised that our core key stakeholders were integral to our response. When compared to the previous 12 months, our recruitment numbers dropped markedly in early phases of the response but recovered over time, as we accommodated internal and external impacts. CONCLUSION: Our experience of agility as a necessity, adapting to support patients, and managing both clinical research activity and sponsors during the height of the pandemic response is presented here in order to inform future disaster response planning by clinical trial organisations.

124I-PET/CT-Guided Diagnosis and Personalized Treatment of Metastatic Papillary Thyroid Cancer to the Pancreas.

ABSTRACT: Metastasis to the pancreas from differentiated thyroid carcinoma is rare. A new pancreatic lesion was identified on surveillance imaging of a man with metastatic papillary thyroid carcinoma 7 years after initial diagnosis. Imaging with 124I-PET/CT was performed to noninvasively confirm metastatic thyroid cancer and provide prospective dosimetry to guide selection of a safe and effective administered activity of 131I. This case demonstrates the emerging role of 124I-PET/CT as a useful diagnostic scan, pretherapy scan, and dosimetric tool to deliver personalized therapy for patients with metastatic thyroid cancer.

Volatile organic compound breath testing detects in-situ squamous cell carcinoma of bronchial and laryngeal regions and shows distinct profiles of each tumour.

Volatile organic compound (VOC) breath testing of lung and head and neck squamous cell carcinoma (SCC) has been widely studied, however little is known regarding VOC profiles of in-situ SCC. A prospective study of VOC in patients with histologically proven SCC, either in-situ or advanced, and controls. Breath samples were analysed using the E-nose Cyranose ®320 and by gas chromatography/mass spectroscopy. Predictive models were developed using bootstrap forest using all 32 sensors. Data from 55 participants was analysed: 42 SCC cases comprising 20 bronchial (10 in-situ, 10 advanced) and 22 laryngeal (12 in-situ, 10 advanced), and 13 controls. There were 32 (76%) male SCC cases with mean age 63.6 (SD = 9.5) compared with 11 (85%) male controls with mean age 61.9 (SD = 10.1). Predictive models for in situ cases had good sensitivity and specificity compared to controls (overall, 95% and 69%; laryngeal, 100% and 85%; bronchial, 77% and 80%). When distinguishing in-situ and advanced tumours, sensitivity and specificity 82% and 75% respectively. For different tumour types (bronchial versus advanced laryngeal) sensitivity and specificity were 100% and 80% respectively. VOCs isolated from in-situ cancers included some previously demonstrated in advanced cancers and some novel VOCs. In-situ bronchial and laryngeal cancer can be detected by VOC analysis. Distinction from normal controls and between the two tumour types could allow screening in high risk groups for these curable lesions.

Improving guideline sensitivity and specificity for the identification of proactive gastrostomy placement in patients with head and neck cancer.

BACKGROUND: Swallowing and nutrition guidelines for patients with head and neck cancer are available for identification of proactive gastrostomy placement in patients with high nutritional risk. The purpose of this study was to investigate improvements to the validity of these guidelines. METHODS: A multivariate analysis was fitted to the original dataset (n = 501) to examine the variables that may predict gastrostomy placement (eg, tumor site, treatment, sex, and age). Using these factors, the high risk category was modified and retrospectively validated in the same cohort to provide new measures of sensitivity and specificity. RESULTS: The following were positive predictors of gastrostomy placement: T3 (p = .01), T4 (p < .001), and chemoradiotherapy (p < .001). Laryngeal (p = .02) and skin cancer (p < .001) were negative predictors. Modification of the high risk definition improved sensitivity to 58% and maintained specificity at 92%. CONCLUSION: Minor modifications to the high risk definition in the guidelines have improved the guideline sensitivity for future use. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1163-E1171, 2016.

Cutaneous carcinoma of the head and neck with clinical features of perineural infiltration treated with radiotherapy.

AIMS: To review the outcome of patients with non-melanomatous carcinoma of the skin of the head and neck with perineural infiltration (PNI) with clinical features treated with radiotherapy. MATERIALS AND METHODS: Between 1991 and 2004, 56 patients with non-melanomatous skin carcinoma with PNI with clinical features were identified from the institution's oncology database. All patients had radiotherapy as either definitive or adjuvant treatment. The factors that affected outcome were analysed. The primary end point was the 5 year relapse-free survival (RFS) from the time of diagnosis of PNI. RESULTS: The overall 5 year RFS for the whole group was 48%. Squamous histology had a more unfavourable outcome than basal cell histology (5 year RFS: 39% versus 80%; P = 0.07). Tumours located in the distribution of the cranial nerves V1 and V2 had a worse outcome than tumours at other sites (5 year RFS: 33% versus 72%, P = 0.056). Those with multiple cranial nerve involvement did worse than those with single nerve involvement (27% versus 62%, P = 0.1). The pattern of relapse was predominantly local (87%), with a low rate (15%) of successful salvage. CONCLUSION: Radiotherapy with or without surgery is curative in about half head and neck cutaneous non-melanomatous carcinomas with clinical PNI. The frequent local failure suggests that improvements in local treatment are required.

The impact of preradiation residual disease volume on time to locoregional failure in cutaneous Merkel cell carcinoma--a TROG substudy.

PURPOSE: This study evaluated the impact of margin status and gross residual disease in patients treated with chemoradiation therapy for high-risk stage I and II Merkel cell cancer (MCC). METHODS AND MATERIALS: Data were pooled from 3 prospective trials in which patients were treated with 50 Gy in 25 fractions to the primary lesion and draining lymph nodes and 2 schedules of carboplatin based chemotherapy. Time to locoregional failure was analyzed according to the burden of disease at the time of radiation therapy, comparing patients with negative margins, involved margins, or macroscopic disease. RESULTS: Analysis was performed on 88 patients, of whom 9 had microscopically positive resection margins and 26 had macroscopic residual disease. The majority of gross disease was confined to nodal regions. The 5-year time to locoregional failure, time to distant failure, time to progression, and disease-specific survival rates for the whole group were 73%, 69%, 62%, and 66% respectively. The hazard ratio for macroscopic disease at the primary site or the nodes was 1.25 (95% confidence interval 0.57-2.77), P=.58. CONCLUSIONS: No statistically significant differences in time to locoregional failure were identified between patients with negative margins and those with microscopic or gross residual disease. These results must, however, be interpreted with caution because of the limited sample size.

Primary chemoradiotherapy for oral cavity squamous cell carcinoma.

OBJECTIVES: To evaluate the survival of patients with oral cavity squamous cell carcinoma (SCC) treated with chemoradiotherapy (CRT) or radiotherapy (RT). To record the rate of osteoradionecrosis (ORN) and need for alternative feeding of patients with oral cavity cancer treated with CRT or RT. MATERIALS AND METHODS: All patients with first presentation of oral cavity SCC treated with CRT or RT only at the Royal Brisbane & Women's Hospital (RBWH) between 2000 and 2007 were included. Patient Demographics (age, sex), ACE-27 Co-morbidity index, Staging (TNM staging system), Type of Chemotherapy and Dose of RT, Overall Survival (OS) and Disease-Specific Survival (DSS), Attempt at Salvage, development of distant metastases, development of ORN and success of treatment for ORN and requirement for alternative feeding (PEG/NGT) were recorded. RESULTS: Fifty-four patients met the inclusion criteria. One patient died due to toxicity of treatment. The 5-year OS was 29%. The 5-year DSS was 30%. The rate of ORN amongst survivors was 36%. CONCLUSIONS: CRT is successful in a small number of patients with oral cavity SCC. When compared to the published literature, surgery with or without post-operative RT has better survival rates. Salvage surgery does not appear to be a viable option for management of recurrence post CRT. The consequences of treatment, namely ORN and need for alternative feeding, are high.

Perineural infiltration of cutaneous squamous cell carcinoma and basal cell carcinoma without clinical features.

PURPOSE: To review the factors that influence outcome and patterns of relapse in patients with cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with perineural infiltration (PNI) without clinical or radiologic features, treated with surgery and radiotherapy. METHODS AND MATERIALS: Between 1991 and 2004, 222 patients with SCC or BCC with PNI on pathologic examination but without clinical or radiologic PNI features were identified. Charts were reviewed retrospectively and relevant data collected. All patients were treated with curative intent; all had radiotherapy, and most had surgery. The primary endpoint was 5-year relapse-free survival from the time of diagnosis. RESULTS: Patients with SCC did significantly worse than those with BCC (5-year relapse-free survival, 78% vs. 91%; p < 0.01). Squamous cell carcinoma with PNI at recurrence did significantly worse than de novo in terms of 5-year local failure (40% vs. 19%; p < 0.01) and regional relapse (29% vs. 5%; p < 0.01). Depth of invasion was also a significant factor. Of the PNI-specific factors for SCC, focal PNI did significantly better than more-extensive PNI, but involved nerve diameter or presence of PNI at the periphery of the tumor were not significant factors. CONCLUSIONS: Radiotherapy in conjunction with surgery offers an acceptable outcome for cutaneous SCC and BCC with PNI. This study suggests that focal PNI is not an adverse feature.

Dosimetric effect of external beam planning preceding combined high-dose-rate brachytherapy of the prostate.

PURPOSE: The sequencing of external beam radiotherapy (EBRT) and a high-dose-rate brachytherapy (HDRB) boost is often interchangeable in clinical practice. When given before EBRT, HDRB could induce volume alterations in the prostate, which may have significant implications for EBRT dosimetry. We aimed to assess the influence of HDRB on prostate volume and, hence, prostate dosing via subsequent EBRT. METHODS AND MATERIALS: Fifteen men had both pre- and post-HDRB CT performed followed by EBRT. After deidentification, the clinical target volume (CTV) was defined on each CT by a single-blinded observer. Volumes were compared for the pre- and post-HDRB scans in each patient. Radiotherapy planning was performed using the prebrachytherapy volumes aiming for the planning target volume (PTV) to be covered by 43.7Gy. After soft-tissue coregistration, this plan was also applied to the postbrachytherapy volumes. RESULTS: Median volume increase was 35.4% for the CTV after HDRB. No patient experienced a decrease in CTV volume (range, 0-79% volume increase; p-value<0.001). Median volume increase was 26.1% for the PTVs, with no volume decrease observed (range, 8-56%; p<0.001). PTV proportion achieving dose target (V43.7Gy) decreased by median of 7% (range, 0-21.5%; p=0.004). The minimum dose to the PTV (D(100)%) decreased by a median of 6Gy (range, 0.5-16Gy; p<0.001). CONCLUSIONS: Insertion of HDRB catheters exerts substantial acute volumetric distortion on the prostate. EBRT planning performed on the basis of pre-HDRB imaging only inherently risks underdosing tumor. Planning adjustments based on repeat CT, or dedicated post-HDBT planning, is warranted for men managed with HDRB before EBRT.

Effect of radiotherapy dose and volume on relapse in Merkel cell cancer of the skin.

PURPOSE: To assess the effect of radiotherapy (RT) dose and volume on relapse patterns in patients with Stage I-III Merkel cell carcinoma (MCC). PATIENTS AND METHODS: This was a retrospective analysis of 112 patients diagnosed with MCC between January 2000 and December 2005 and treated with curative-intent RT. RESULTS: Of the 112 evaluable patients, 88% had RT to the site of primary disease for gross (11%) or subclinical (78%) disease. Eighty-nine percent of patients had RT to the regional lymph nodes; in most cases (71%) this was for subclinical disease in the adjuvant or elective setting, whereas 21 patients (19%) were treated with RT to gross nodal disease. With a median follow-up of 3.7 years, the 2-year and 5-year overall survival rates were 72% and 53%, respectively, and the 2-year locoregional control rate was 75%. The in-field relapse rate was 3% for primary disease, and relapse was significantly lower for patients receiving >or=50 Gy (hazard ratio [HR] = 0.22; 95% confidence interval [CI], 0.06-0.86). Surgical margins did not affect the local relapse rate. The in-field relapse rate was 11% for RT to the nodes, with dose being significant for nodal gross disease (HR = 0.24; 95% CI, 0.07-0.87). Patients who did not receive elective nodal RT had a much higher rate of nodal relapse compared with those who did (HR = 6.03; 95% CI, 1.34-27.10). CONCLUSION: This study indicates a dose-response for subclinical and gross MCC. Doses of >or=50 Gy for subclinical disease and >or=55 Gy for gross disease should be considered. The draining nodal basin should be treated in all patients.

Radiotherapy for perineural invasion in cutaneous head and neck carcinomas: toward a risk-adapted treatment approach.

BACKGROUND: We retrospectively reviewed outcomes in patients treated with radiotherapy (RT) for cutaneous head and neck carcinoma with perineural invasion (PNI), with the aim of developing risk-adapted treatment guidelines. METHODS: A total of 118 patients were treated with RT between April 1992 and July 2000. Ninety-seven patients had PNI discovered through histology (pPNI) and 21 patients had symptoms/signs of PNI (cPNI). All received RT (median dose, 55 Gy; range, 17-74): 114 postoperatively and 4 definitively. Median follow-up was 84 months (range, 4-201). RESULTS: The 5-year local control (LC) rates were 90% with pPNI and 57% with cPNI (p < .0001). The pPNI and cPNI groups also differed in relapse-free survival (76% vs 46%, p = .003), disease-specific survival (90% vs 76%, p = .002), and overall survival (69% vs 57%, p = .03). pPNI patients with BCC histology (n = 42) had better LC (97% vs 84%, p = .02) than pPNI SCC (n = 55). CONCLUSION: Surgery plus RT provides a high rate of LC in patients with pPNI, particularly those with BCC. Therapeutic improvements are needed for patients with cPNI.

Weekly carboplatin reduces toxicity during synchronous chemoradiotherapy for Merkel cell carcinoma of skin.

PURPOSE: The toxicity of radiotherapy (RT) combined with weekly carboplatin and adjuvant carboplatin and etoposide was prospectively assessed in a group of patients with high-risk Stage I and II Merkel cell carcinoma of the skin. This regimen was compared with the Trans-Tasman Radiation Oncology Group 96:07 study, which used identical eligibility criteria but carboplatin and etoposide every 3 weeks during RT. PATIENTS AND METHODS: Patients were eligible if they had disease localized to the primary site and lymph nodes, with high-risk features. RT was delivered to the primary site and lymph nodes to a dose of 50 Gy and weekly carboplatin (area under the curve of 2) was given during RT. This was followed by three cycles of carboplatin and etoposide. A total of 18 patients were entered into the study, and their data were compared with the data from 53 patients entered into the Trans-Tasman Radiation Oncology Group 96:07 study. RESULTS: Involved lymph nodes (Stage II) were present in 14 patients (77%). Treatment was completed as planned in 16 patients. The weekly carboplatin dose was delivered in 17 patients, and 15 were able to complete all three cycles of adjuvant carboplatin and etoposide. Grade 3 and 4 neutrophil toxicity occurred in 7 patients, but no cases of febrile neutropenia developed. Compared with the Trans-Tasman Radiation Oncology Group 96:07 protocol (19 of 53 cases of febrile neutropenia), the reduction in the febrile neutropenia rate (p = 0.003) and decrease in Grade 3 skin toxicity (p = 0.006) were highly statistically significant. CONCLUSION: The results of our study have shown that weekly carboplatin at this dosage is a safe way to deliver synchronous chemotherapy during RT for MCC and results in a marked reduction of febrile neutropenia and Grade 3 skin toxicity compared with the three weekly regimen.

Lymphoproliferative disease of the ocular adnexa: a clinical and pathologic study with statistical analysis of 69 patients.

PURPOSE: To evaluate the clinical features, treatment, and outcomes of a cohort of patients with ocular adnexal lymphoproliferative disease classified according to the World Health Organization modification of the Revised European-American Classification of Lymphoid neoplasms and to perform a robust statistical analysis of these data. METHODS: Sixty-nine cases of ocular adnexal lymphoproliferative disease, seen in a tertiary referral center from 1992 to 2003, were included in the study. Lesions were classified by using the World Health Organization modification of the Revised European-American Classification of Lymphoid neoplasms classification. Outcome variables included disease-specific survival, relapse-free survival, local control, and distant control. RESULTS: Stage IV disease at presentation, aggressive lymphoma histology, the presence of prior or concurrent systemic lymphoma at presentation, and bilateral adnexal disease were significant predictors for reduced disease-specific survival, local control, and distant control. Multivariate analysis found that aggressive histology and bilateral adnexal disease had significantly reduced disease-specific survival. CONCLUSIONS: The typical presentation of adnexal lymphoproliferative disease is with a painless mass, swelling, or proptosis; however, pain and inflammation occurred in 20% and 30% of patients, respectively. Stage at presentation, tumor histology, primary or secondary status, and whether the process was unilateral or bilateral were significant variables for disease outcome. In this study, distant spread of lymphoma was lower in patients who received greater than 20 Gy of orbital radiotherapy.

Effect of surgery on normal tissue toxicity in patients treated with accelerated radiotherapy.

The aim of this study was to assess the effect of surgery on normal tissue toxicity in head and neck cancer patients treated with accelerated radiotherapy. Toxicity data from two trials of accelerated radiotherapy were compared. The first group was taken from a phase III trial of definitive radiotherapy and the second group from a phase II trial of postoperative radiotherapy. The general eligibility criteria (apart from surgery), data collection and radiotherapy details for both trials were similar. The definitive group included 172 eligible patients and the postoperative group 52 eligible patients. At 3 weeks into treatment, by which time the dose and rate of dose accumulation were identical, there was no difference in acute toxicity. Analysis of late toxicity showed greater subcutaneous fibrosis in the postoperative group.