Net survival of men with localized prostate cancer after LDR brachytherapy.

OBJECTIVES: To compare survival of patients who received LDR prostate brachytherapy relative to that of peers in the general population of England, UK. PATIENTS AND METHODS: Net survival was estimated for 2472 cases treated between 2002 and 2016 using population-based analysis guidelines. Life tables adjusted for social deprivation in England from the Office for National Statistics were used to match patients by affluence based on their postcode. RESULTS: The median (range) age at time of brachytherapy was 66 (55-84) years, 84% resided in Southeast England, 51% under an index of deprivation quintile 5 (most affluent), 55% were clinical stage T1 and the remainder T2. Death from any cause occurred in 270 patients at a median (range) of 7 (1-17) years postimplant. Five and 10-year estimates (95% CI) of overall survival were 96% (95-97) and 90% (89-92), and net survival 103% (102-104) and 109% (107-110) respectively. The net survival remained above 100% in all age-at-treatment and clinical stage groups. CONCLUSION: Net survival above 100% indicates patients survive longer than the matched general population. The study shows for the first time the net survival of patients treated with a radical therapy for localized prostate cancer in England. The impact of treatment choice on the long-term net survival advantage requires further investigation.

BMI and HbA1c are metabolic markers for pancreatic cancer: Matched case-control study using a UK primary care database.

BACKGROUND: Weight loss, hyperglycaemia and diabetes are known features of pancreatic cancer. We quantified the timing and the amount of changes in body mass index (BMI) and glycated haemoglobin (HbA1c), and their association with pancreatic cancer from five years before diagnosis. METHODS: A matched case-control study was undertaken within 590 primary care practices in England, United Kingdom. 8,777 patients diagnosed with pancreatic cancer (cases) between 1st January 2007 and 31st August 2020 were matched to 34,979 controls by age, gender and diabetes. Longitudinal trends in BMI and HbA1c were visualised. Odds ratios adjusted for demographic and lifestyle factors (aOR) and 95% confidence intervals (CI) were calculated with conditional logistic regression. Subgroup analyses were undertaken according to the diabetes status. RESULTS: Changes in BMI and HbA1c observed for cases on longitudinal plots started one and two years (respectively) before diagnosis. In the year before diagnosis, a 1 kg/m2 decrease in BMI between cases and controls was associated with aOR for pancreatic cancer of 1.05 (95% CI 1.05 to 1.06), and a 1 mmol/mol increase in HbA1c was associated with aOR of 1.06 (1.06 to 1.07). ORs remained statistically significant (p < 0.001) for 2 years before pancreatic cancer diagnosis for BMI and 3 years for HbA1c. Subgroup analysis revealed that the decrease in BMI was associated with a higher pancreatic cancer risk for people with diabetes than for people without (aORs 1.08, 1.06 to 1.09 versus 1.04, 1.03 to 1.05), but the increase in HbA1c was associated with a higher risk for people without diabetes than for people with diabetes (aORs 1.09, 1.07 to 1.11 versus 1.04, 1.03 to 1.04). CONCLUSIONS: The statistically significant changes in weight and glycaemic control started three years before pancreatic cancer diagnosis but varied according to the diabetes status. The information from this study could be used to detect pancreatic cancer earlier than is currently achieved. However, regular BMI and HbA1c measurements are required to facilitate future research and implementation in clinical practice.

Is hemi-gland focal LDR brachytherapy as effective as whole-gland treatment for unilateral prostate cancer?

PURPOSE: The Hemi-Ablative Prostate Brachytherapy (HAPpy) trial evaluated hemi-gland (HG) low-dose-rate prostate brachytherapy (LDR-PB) as a focal approach to control unilateral localized prostate cancer and reduce treatment-related toxicity at 2-years postimplant. Herewith we present further outcomes with a minimum of 5 years post-implant follow-up. METHODS AND MATERIALS: Outcomes of 30 HG implants and 362 whole-gland (WG) brachytherapy controls were monitored with IPSS, urinary Quality-of-Life (QoLU), GI component of EORTC-PR25 (QoLB), and IIEF-5 instruments, and PSA values. The median (range) follow-up for HG and WG cases was 72 (60-96) months and 84 (24-144) months respectively. RESULTS: The IPSS was significantly reduced in HG relative to WG patients and trends indicating improved bowel QoL and erectile function were observed. The mean of change in PSA from baseline to last follow-up was -5.6 and -6.5 in HG and WG respectively (p = 0.1). The mean time to nadir was 4.2 and 4.8 years in HG and WG respectively (p = 0.06). Over time PSA in HG patients mirrored the sustained decline observed in WG cases but levels were higher by an average 0.5 ng/ml over WG controls (p < 0.001). Treatment failure occurred in 2 (6.7%) HG patients and in 20 (5.5%) WG cases. Five-year relapse-free survival was 97% in both groups (p = 0.7). CONCLUSIONS: At 5 years postimplant HG LDR-PB was as effective as WG treatment for control of unilateral localized prostate cancer with moderate improvement in treatment-related symptoms. Importantly, PSA is a valuable marker to assess disease control in this form of focal therapy.

Healthcare Professional and Patient Perceptions of Changes in Colorectal Cancer Care Delivery During the COVID-19 Pandemic and Impact on Health Inequalities.

BACKGROUND: The COVID-19 pandemic changed the way in which people were diagnosed and treated for cancer. We explored healthcare professional and patient perceptions of the main changes to colorectal cancer delivery during the COVID-19 pandemic and how they impacted on socioeconomic inequalities in care. METHODS: In 2020, using a qualitative approach, we interviewed patients (n = 15) who accessed primary care with colorectal cancer symptoms and were referred for further investigations. In 2021, we interviewed a wide range of healthcare professionals (n = 30) across the cancer care pathway and gathered national and local documents/guidelines regarding changes in colorectal cancer care. RESULTS: Changes with the potential to exacerbate inequalities in care, included: the move to remote consultations; changes in symptomatic triage, new COVID testing procedures/ways to access healthcare, changes in visitor policies and treatment (e.g., shorter course radiotherapy). Changes that improved patient access/convenience or the diagnostic process have the potential to reduce inequalities in care. DISCUSSION: Changes in healthcare delivery during the COVID-19 pandemic have the ongoing potential to exacerbate existing health inequalities due to changes in how patients are triaged, changes to diagnostic and disease management processes, reduced social support available to patients and potential over-reliance on digital first approaches. We provide several recommendations to help mitigate these harms, whilst harnessing the gains.

Socioeconomic differences in help seeking for colorectal cancer symptoms during COVID-19: a UK-wide qualitative interview study.

BACKGROUND: COVID-19 has led to rapid changes in healthcare delivery, raising concern that these changes may exacerbate existing inequalities in patient outcomes. AIM: To understand how patients' help-seeking experiences in primary care for colorectal cancer symptoms during COVID-19 were affected by their socioeconomic status (SES). DESIGN AND SETTING: Qualitative semi-structured interviews with males and females across the UK, recruited using purposive sampling by SES. METHOD: Interviews were carried out with 39 participants (20 higher SES; 19 lower SES) who contacted primary care about possible symptoms of colorectal cancer during COVID-19. Data were analysed using framework analysis followed by comparative thematic analysis to explore differences between groups. RESULTS: Three themes were identified with differences between SES groups: 1) how people decided to seek medical help through appraisal of symptoms; 2) how people navigated services; and 3) impact of COVID-19 on how patients interacted with healthcare professionals. The lower SES group expressed uncertainty appraising symptoms and navigating services (in terms of new processes resulting from COVID-19 and worries about infection). There was also potential for increased disparity in diagnosis and management, with other methods of getting in touch (for example, email or 111) taken up more readily by higher SES patients. CONCLUSION: The findings suggest that COVID-19 exacerbated disparities between higher and lower SES participants. This study raises awareness around challenges in help seeking in the context of the pandemic, which are likely to persist (post-COVID-19) as healthcare systems settle on new models of care (for example, digital). Recommendations are provided to reduce inequalities of care.

Long-term survival after low-dose-rate brachytherapy for prostate cancer: the Royal Surrey experience.

OBJECTIVES: To assess the long-term treatment efficacy of low-dose-rate (LDR) brachytherapy for the treatment of localized prostate cancer. PATIENTS AND METHODS: Cause-of-death annotation in our prospective database was supplemented with death certificate information obtained via an internal audit of patients treated from 1999 to 2017 with LDR prostate brachytherapy as monotherapy or as combination with androgen deprivation therapy and/or external beam radiotherapy. Overall and disease-specific survival were the primary outcomes, estimated with Kaplan-Meier and competing risks multi-state models. Clinical variables influencing mortality were assessed with Cox proportional hazards regression in a sub-analysis of men to assess the predictive value of prostate-specific antigen (PSA) level at 48 months post implant. RESULTS: The audit process began in October 2017 and culminated in June 2020 with a curated series of 2936 patients. All-cause and prostate cancer-specific death prevalence were 11% and 2.9%, respectively. The median (range) follow-up time was 10 (3-21) years and the median (range) time to death from any cause was 9 (3-21) years. At 15 years post implant the overall and prostate cancer-specific survival probability were 81% and 95%, respectively. The 15-year cumulative incidence rates of death not due and due to prostate cancer were 14% and 5%, respectively. A greater risk of death due to prostate cancer was conferred by increasing age at therapy (hazard ratio [HR] 1.1, P < 0.001), advanced clinical stages relative to T1a-T2a (HR 1.9, P = 0.048 for T2b; HR 2.7, P = 0.023 for T2c-T3b) and a 48-month PSA level >1.0 ng/mL (HR 6.8, P < 0.001). CONCLUSION: This study constitutes the largest retrospective analyses of long-term mortality outcomes from prospectively collected prostate brachytherapy data and confirms the excellent treatment efficacy of LDR prostate brachytherapy for localized prostate cancer. T2 clinical stage subdivisions and 48-month PSA level >1.0 ng/mL appear to be strong indicators of prostate cancer-related survival.

Randomised controlled trial to investigate the effectiveness of the symptom management after radiotherapy (SMaRT) group intervention to ameliorate lower urinary tract symptoms in men treated for prostate cancer.

PURPOSE: To evaluate the effectiveness of the symptom management after radiotherapy (SMaRT) group intervention to improve urinary symptoms in men with prostate cancer. METHODS: The randomised controlled trial (RCT) recruited men from one radiotherapy centre in the UK after curative radiotherapy or brachytherapy and with moderate to severe urinary symptoms defined as scores ≥ 8 on the International Prostate Symptom Score (IPSS) questionnaire. Sixty-three men were randomised either; to SMaRT, a 10-week symptom-management intervention including group support, education, pelvic floor muscle exercises, or a care-as-usual group. The primary outcome was the IPSS at 6 months from baseline assessment. Secondary outcomes were IPSS at 3 months, and International Continence Society Male Short Form (ICS), European Organisation for Research and Treatment of Cancer Quality of Life prostate scale (EORTC QLQ-PR25), EORTC QLQ-30 and Self-Efficacy for Symptom Control Inventory (SESCI) at 3 and 6 months from baseline. Analysis of covariance (ANCOVA) was used to analyse the effect of the intervention. RESULTS: SMaRT group intervention did not improve urinary symptoms as measured by IPSS at 6-months. The adjusted difference was - 2.5 [95%CI - 5.0 to 0.0], p = 0.054. Significant differences were detected at 3 months in ICS voiding symptoms (- 1.1 [- 2.0 to - 0.2], p = 0.017), ICS urinary incontinence (- 1.0 [- 1.8 to - 0.1], p = 0.029) and SESCI managing symptoms domain (13.5 [2.5 to 24.4], p = 0.017). No differences were observed at 6 months. CONCLUSIONS: SMaRT group intervention provided short-term benefit in urinary voiding and continence and helped men manage symptoms but was not effective long term.

Vascular endothelial growth factor (VEGF) targeting therapy for persistent, recurrent, or metastatic cervical cancer.

BACKGROUND: Cervical cancer ranks as the fourth leading cause of death from cancer in women. Historically, women with metastatic or recurrent cervical cancer have had limited treatment options. New anti-angiogenesis therapies, such as vascular endothelial growth factor (VEGF) targeting agents, offer an alternative strategy to conventional chemotherapy; they act by inhibiting the growth of new blood vessels, thereby restricting tumour growth by blocking the blood supply. OBJECTIVES: To assess the benefits and harms of VEGF targeting agents in the management of persistent, recurrent, or metastatic cervical cancer. SEARCH METHODS: We performed searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, online registers of clinical trials, and abstracts of scientific meetings up until 27 May 2020. SELECTION CRITERIA: We examined randomised controlled trials (RCTs) that evaluated the use of VEGF targeting agents alone or in combination with conventional chemotherapy or other VEGF targeting agents. DATA COLLECTION AND ANALYSIS: Three review authors independently screened the results of search strategies, extracted data, assessed risk of bias, and analysed data according to the standard methods expected by Cochrane. The certainty of evidence was assessed via the GRADE approach. MAIN RESULTS: A total of 1634 records were identified. From these, we identified four studies with a total of 808 participants for inclusion. We also identified two studies that were awaiting classification and nine ongoing studies. Bevacizumab plus chemotherapy versus chemotherapy Treatment with bevacizumab plus chemotherapy may result in lower risk of death compared to chemotherapy alone (hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.62 to 0.95; 1 study, 452 participants; low-certainty evidence). However, there are probably more specific adverse events when compared to chemotherapy alone, including gastrointestinal perforations or fistulae (risk ratio (RR) 18.00, 95% CI 2.42 to 133.67; 1 study, 440 participants; moderate-certainty evidence); serious thromboembolic events (RR 4.5, 95% CI 1.55 to 13.08; 1 study, 440 participants; moderate-certainty evidence); and hypertension (RR 13.75, 95% CI 5.07 to 37.29; 1 study, 440 participants; moderate-certainty evidence). There may also be a higher incidence of serious haemorrhage (RR 5.00, 95% CI 1.11 to 22.56; 1 study, 440 participants; low-certainty evidence). In addition, the incidence of serious adverse events is probably higher (RR 1.44, 95% CI 1.16 to 1.79; 1 study, 439 participants; moderate-certainty evidence). The incremental cost-effectiveness ratio was USD 295,164 per quality-adjusted life-year (1 study, 452 participants; low-certainty evidence). Cediranib plus chemotherapy versus chemotherapy Treatment with cediranib plus chemotherapy may or may not result in similar risk of death when compared to chemotherapy alone (HR 0.94, 95% CI 0.53 to 1.65; 1 study, 69 participants; low-certainty evidence). We found very uncertain results for the incidences of specific adverse events, including gastrointestinal perforations or fistulae (RR 3.27, 95% CI 0.14 to 77.57; 1 study, 67 participants; very low-certainty evidence); serious haemorrhage (RR 5.45, 95% CI 0.27 to 109.49; 1 study, 67 participants; very low-certainty evidence); serious thromboembolic events (RR 3.41, 95% CI 0.14 to 80.59; 1 study, 60 participants; very low-certainty evidence); and serious hypertension (RR 0.36, 95% CI 0.02 to 8.62; 1 study, 67 participants; very low-certainty evidence). In addition, there may or may not be a similar incidence of serious adverse events compared to chemotherapy alone (RR 1.15, 95% CI 0.75 to 1.78; 1 study, 67 participants; low-certainty evidence). Apatinib plus chemotherapy or chemotherapy/brachytherapy versus chemotherapy or chemotherapy/brachytherapy Treatment with apatinib plus chemotherapy or chemotherapy/brachytherapy may or may not result in similar risk of death compared to chemotherapy alone or chemotherapy/brachytherapy alone (HR 0.90, 95% CI 0.51 to 1.60; 1 study, 52 participants; low-certainty evidence). However, hypertension events may occur at a higher incidence as compared to chemotherapy alone or chemotherapy/brachytherapy alone (RR 5.14, 95% CI 1.28 to 20.73; 1 study, 52 participants; low-certainty evidence). Pazopanib plus lapatinib versus lapatinib Treatment with pazopanib plus lapatinib may result in higher risk of death compared to lapatinib alone (HR 2.71, 95% CI 1.16 to 6.31; 1 study, 117 participants; low-certainty evidence). We found very uncertain results for the incidences of specific adverse events, including gastrointestinal perforations or fistulae (RR 2.00, 95% CI 0.19 to 21.59; 1 study, 152 participants; very low-certainty evidence); haemorrhage (RR 2.00, 95% CI 0.72 to 5.58; 1 study, 152 participants; very low-certainty evidence); and thromboembolic events (RR 3.00, 95% CI 0.12 to 72.50; 1 study, 152 participants; very low-certainty evidence). In addition, the incidence of hypertension events is probably higher (RR 12.00, 95% CI 2.94 to 49.01; 1 study, 152 participants; moderate-certainty evidence). There may or may not be a similar incidence of serious adverse events as compared to lapatinib alone (RR 1.45, 95% CI 0.94 to 2.26; 1 study, 152 participants; low-certainty evidence). Pazopanib versus lapatinib Treatment with pazopanib may or may not result in similar risk of death as compared to lapatinib (HR 0.96, 95% CI 0.67 to 1.38; 1 study, 152 participants; low-certainty evidence). We found very uncertain results for the incidences of specific adverse events, including gastrointestinal perforations or fistulae (RR 1.03, 95% CI 0.07 to 16.12; 1 study, 150 participants; very low-certainty evidence); haemorrhage (RR 1.03, 95% CI 0.31 to 3.40; 1 study, 150 participants; very low-certainty evidence); and thromboembolic events (RR 3.08, 95% CI 0.13 to 74.42; 1 study, 150 participants; very low-certainty evidence). In addition, the incidence of hypertension events is probably higher (RR 11.81, 95% CI 2.89 to 48.33; 1 study, 150 participants; moderate-certainty evidence). The risk of serious adverse events may or may not be similar as compared to lapatinib (RR 1.31, 95% CI 0.83 to 2.07; 1 study, 150 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: We found low-certainty evidence in favour of the use of bevacizumab plus chemotherapy. However, bevacizumab probably increases specific adverse events (gastrointestinal perforations or fistulae, thromboembolic events, hypertension) and serious adverse events. We found low-certainty evidence that does not support the use of cediranib plus chemotherapy, apatinib plus chemotherapy, apatinib plus chemotherapy/brachytherapy, or pazopanib monotherapy. We found low-certainty evidence suggesting that pazopanib plus lapatinib worsens outcomes. The VEGF inhibitors apatinib and pazopanib may increase the probability of hypertension events.

Primary Care Prostate Cancer Case Ascertainment.

Although routine healthcare data are not collected for research, they are increasingly used in epidemiology and are key real-world evidence for improving healthcare. This study presents a method to identify prostate cancer cases from a large English primary care database. 19,619 (1.3%) men had a code for prostate cancer diagnosis. Codes for medium and high Gleason grading enabled identification of additional 94 (0.5%) cases. Many studies do not report codes used to identify patients, and if published, the lists of codes differ from study to study. This can lead to poor research reproducibility and hinder validation. This work demonstrates that carefully developed comprehensive lists of clinical codes can be used to identify prostate cancer; and that approaches that do not solely rely on clinical codes such as ontologies or data linkage should also be considered.

Modern Brachytherapy.

Brachytherapy involves the placement of radioactive sources within or very close to the tumor. This placement allows a high dose of radiotherapy to be delivered to the tumor while sparing the surrounding normal tissue. The delivery of brachytherapy has changed markedly over the years, with newer radioactive sources making delivery safer, image guidance techniques allowing more accurate placement of sources, and advanced planning systems allowing brachytherapy to be truly adaptive. This article explores the most modern techniques and current uses of brachytherapy in the treatment of gynecological, prostate, breast, rectal, and skin cancers.

Improving dose delivery by adding interstitial catheters to fixed geometry applicators in high-dose-rate brachytherapy for cervical cancer.

PURPOSE: Image-guided brachytherapy (IGBT) is an essential component of the treatment of locally advanced cervical cancer. Interstitial (IS) catheters are being increasingly used for bulkier tumors. We have retrospectively assessed the dosimetric impact of IS catheters. METHODS AND MATERIALS: All patients who received IGBT for cervical cancer between August 2014 and February 2017 were identified. Clinical and dosimetric data were collected. Patients were grouped into the intracavitary (IC) cohort or the IC and IS implant (IC/IS) cohort. Ten patients who had been treated with IS catheters (IC/IS plan) had their brachytherapy replanned without IS catheters (IC plan). The total D90% received by the high-risk clinical target volume (CTVHR) and the D2cm3 (minimum dose received by the most irradiated 2 cm3) to the bladder, bowel, sigmoid, and rectum were compared. RESULTS: Forty-two patients received IGBT in this period. Seventy-four percent of patients were treated with IS catheters. Sixty-one percent of patients in the IC/IS cohort had CTVHR volumes ≥30 cm3 at Fraction 1 compared to 18% in the IC cohort (p = 0.014). There was no difference in cumulative D90% to CTVHR between the IC/IS cohort and the IC cohort. The replanned brachytherapy showed that the cumulative CTVHRD90% was on average 5.8 Gy higher when IS catheters were used (mean CTVHRD90% 86.1 compared to 80.3 Gy, p < 0.001). The D2cm3 to the organs at risk was not significantly increased. CONCLUSIONS: IS catheters allow the dose to the CTVHR to be escalated significantly without increasing the dose to the bladder, bowel, sigmoid, and rectum in patients with bulky tumors.

Improving the efficiency of image guided brachytherapy in cervical cancer.

Brachytherapy is an essential component of the treatment of locally advanced cervical cancers. It enables the dose to the tumor to be boosted whilst allowing relative sparing of the normal tissues. Traditionally, cervical brachytherapy was prescribed to point A but since the GEC-ESTRO guidelines were published in 2005, there has been a move towards prescribing the dose to a 3D volume. Image guided brachytherapy has been shown to reduce local recurrence, and improve survival and is optimally predicated on magnetic resonance imaging. Radiological studies, patient workflow, operative parameters, and intensive therapy planning can represent a challenge to clinical resources. This article explores the ways, in which 3D conformal brachytherapy can be implemented and draws findings from recent literature and a well-developed hospital practice in order to suggest ways to improve the efficiency and efficacy of a brachytherapy service. Finally, we discuss relatively underexploited translational research opportunities.

Evaluation of the Risk of Grade 3 Oral and Pharyngeal Dysphagia Using Atlas-Based Method and Multivariate Analyses of Individual Patient Dose Distributions.

PURPOSE: The study aimed to apply the atlas of complication incidence (ACI) method to patients receiving radical treatment for head and neck squamous cell carcinomas (HNSCC), to generate constraints based on dose-volume histograms (DVHs), and to identify clinical and dosimetric parameters that predict the risk of grade 3 oral mucositis (g3OM) and pharyngeal dysphagia (g3PD). METHODS AND MATERIALS: Oral and pharyngeal mucosal DVHs were generated for 253 patients who received radiation (RT) or chemoradiation (CRT). They were used to produce ACI for g3OM and g3PD. Multivariate analysis (MVA) of the effect of dosimetry, clinical, and patient-related variables was performed using logistic regression and bootstrapping. Receiver operating curve (ROC) analysis was also performed, and the Youden index was used to find volume constraints that discriminated between volumes that predicted for toxicity. RESULTS: We derived statistically significant dose-volume constraints for g3OM over the range v28 to v70. Only 3 statistically significant constraints were derived for g3PD v67, v68, and v69. On MVA, mean dose to the oral mucosa predicted for g3OM and concomitant chemotherapy and mean dose to the inferior constrictor (IC) predicted for g3PD. CONCLUSIONS: We have used the ACI method to evaluate incidences of g3OM and g3PD and ROC analysis to generate constraints to predict g3OM and g3PD derived from entire individual patient DVHs. On MVA, the strongest predictors were radiation dose (for g3OM) and concomitant chemotherapy (for g3PD).

Outcomes following adjuvant therapy for HER2-positive early breast cancer in the elderly.

A third of breast cancer diagnoses are made in women aged 70 years or over. Historically, older women have been regarded as presenting with tumors that are low grade and hormone sensitive and that are likely to have a good prognosis. However, in those older women whose tumors overexpress the HER2 oncogene, the prognosis is likely to be worse. Under these circumstances, due consideration should be given to adjuvant systemic therapy, including chemotherapy and targeted treatments, in order to minimize risks of disease recurrence. In this article we discuss the evidence base for the role of adjuvant systemic therapy in older women with HER2-positive early breast cancer.