Oncology

Results of a randomized phase III study of dysphagia-optimized intensity modulated radiotherapy (Do-IMRT) versus standard IMRT (S-IMRT) in head and neck cancer (2020)

Posted on by

Type of publication:
Conference abstract

Author(s):
Nutting C.; Rooney K.; Foran B.; *Pettit L.; Beasley M.; Finneran L.; Roe J.; Tyler J.; Roques T.; Cook A.; Petkar I.; Bhide S.; Srinivasan D.; Boon C.; De Winton E.; Frogley R.; Mertens K.; Emson M.; Hall E.

Citation:
Journal of Clinical Oncology; 2020; vol. 38 (no. 15)

Abstract:
Background: Most newly diagnosed oro-& hypopharngeal cancers (OPC, HPC) are treated with (chemo)RT with curative intent but at the consequence of adverse effects on quality of life. CRUK/14/014 investigated if using Do-IMRT to reduce RT dose to the dysphagia/aspiration related structures (DARS) improved swallowing function compared to S-IMRT. Method(s): Patients with T1-4, N0-3, M0 OPC/HPC were randomised 1:1 to S-IMRT (65 Gray (Gy)/30 fractions (f) to primary&nodal tumour; 54Gy/30f to remaining pharyngeal subsite&nodal areas at risk of microscopic disease) or Do-IMRT. The volume of the superior∣dle pharyngeal constrictor muscle (PCM) (OPC) or inferior PCM (HPC) lying outside the high-dose target volume was set a mandatory mean dose constraint in Do-IMRT. Treatment allocation was by minimisation balanced by centre, use of induction/concomitant chemotherapy, tumour site&AJCC stage. Primary endpoint was mean MD Anderson Dysphagia Inventory (MDADI) composite score 12 months after RT with 102 patients needed to detect a 10 point improvement (assuming S-IMRT score of 72, standard deviation (SD) 13.8; 90% power, 2-sided 5% alpha). Patients were blind to treatment allocation. Secondary endpoints included local control. Result(s): 112 patients (56 S-IMRT, 56 Do-IMRT) were randomised from 22 UK centres from 06/2016 to 04/2018. Mean age was 57 years; 80% were male; 97% had OPC; 90% had AJCC stage 3&4 disease; 86% had concomitant chemotherapy only, 4% induction&concomitant and 10% no chemotherapy. 111/112 had RT doses as prescribed (1 patient died before RT). Median of the mean inferior PCM dose was S-IMRT 49.8Gy (IQR 47.1-52.4) vs. Do-IMRT 28.4Gy (21.3-37.4), p < 0.0001; superior∣dle PCM dose was S-IMRT 57.2Gy (56.3-58.3) vs. Do-IMRT 49.7Gy (49.4-49.9), p < 0.0001. Do-IMRT had significantly higher MDADI scores: S-IMRT 70.3 (SD 17.3) vs. Do-IMRT 77.7 (16.1), p = 0.016. 3 local recurrences (1 S-IMRT, 2 Do-IMRT) have been reported. Conclusion(s): Do-IMRT reduced RT dose to the DARS and improved patient reported swallowing function compared with S-IMRT. This is the first randomised study to demonstrate functional benefit of swallow-sparing IMRT in OPC.

Link to full-text [no password required]

Ten-Year Results of FAST: A Randomized Controlled Trial of 5-Fraction Whole-Breast Radiotherapy for Early Breast Cancer (2020)

Posted on by

Type of publication:
Randomised controlled trial

Author(s):
Brunt A.M.; Haviland J.S.; Sydenham M.; Bliss J.M.; *Agrawal R.K.; Algurafi H.; Alhasso A.; Barrett-Lee P.; Passant H.; Bliss P.; Bloomfield D.; Tremlett J.; Bowen J.; Donovan E.; Goodman A.; Harnett A.; Hogg M.; Kumar S.; Quigley M.; Sherwin L.; Stewart A.; Syndikus I.; Tsang Y.; Venables K.; Wheatley D.; Yarnold J.R.

Citation:
Journal of Clinical Oncology; October 2020, 38, no. 28, 3261-3272.

Abstract:
PURPOSE: Previous studies of hypofractionated adjuvant whole-breast radiotherapy for early breast cancer established a 15- or 16-fraction (fr) regimen as standard. The FAST Trial (CRUKE/04/015) evaluated normal tissue effects (NTE) and disease outcomes after 5-fr regimens. Ten-year results are presented. METHOD(S): Women >= 50 years of age with low-risk invasive breast carcinoma (pT1-2 pN0) were randomly assigned to 50 Gy/25 fr (5 weeks) or 30 or 28.5 Gy in 5 fr of 6.0 or 5.7 Gy (1 week). The primary end point was change in photographic breast appearance at 2 and 5 years; secondary end points were physician assessments of NTE and local tumor control. Odds ratios (ORs) from longitudinal analyses compared regimens. RESULT(S): A total of 915 women were recruited from 18 UK centers (2004-2007). Five-year photographs were available for 615/862 (71%) eligible patients. ORs for change in photographic breast appearance were 1.64 (95% CI, 1.08 to 2.49; P = .019) for 30 Gy and 1.10 (95% CI, 0.70 to 1.71; P = .686) for 28.5 Gy versus 50 Gy. alpha/beta estimate for photographic end point was 2.7 Gy (95% CI, 1.5 to 3.9 Gy), giving a 5-fr schedule of 28 Gy (95% CI, 26 to 30 Gy) estimated to be isoeffective with 50 Gy/25 fr. ORs for any moderate/marked physician-assessed breast NTE (shrinkage, induration, telangiectasia, edema) were 2.12 (95% CI, 1.55 to 2.89; P < .001) for 30 Gy and 1.22 (95% CI, 0.87 to 1.72; P = .248) for 28.5 Gy versus 50 Gy. With 9.9 years median follow-up, 11 ipsilateral breast cancer events (50 Gy: 3; 30 Gy: 4; 28.5 Gy: 4) and 96 deaths (50 Gy: 30; 30 Gy: 33; 28.5 Gy: 33) have occurred. CONCLUSION(S): At 10 years, there was no significant difference in NTE rates after 28.5 Gy/5 fr compared with 50 Gy/25 fr, but NTE were higher after 30 Gy/5 fr. Results confirm the published 3-year findings that a once-weekly 5-fr schedule of whole-breast radiotherapy can be identified that appears to be radiobiologically comparable for NTE to a conventionally fractionated regimen.

Link to full-text [open access - no password required]

Altmetrics:

The triple effect of the magseed for localisation of impalpable breast cancer: Significant reduction in re-excision rate, cost saving by reducing further surgery and high patient satisfaction (2020)

Posted on by

Type of publication:
Conference abstract

Author(s):
*Lake B.; *Wilson M.; *Thomas G.; *Williams S.; *Usman T.

Citation:
European Journal of Surgical Oncology; Jun 2020; vol. 46 (no. 6); e12

Abstract:
Introduction: Traditionally impalpable breast cancers have been localised with image guided techniques of wire guidance or ultrasound marking. Magseed is a small magnetic seed which is changing practice of localisation of these cancers. The aim of this study was to see if the change of practice of localisation to Magseed affected patient outcome evaluated by re-excision rate, specimen weight and patient satisfaction. Method(s): A change of practice service evaluation was conducted at the Shrewsbury and Telford Hospital of all patients who had imaged guided wide local excision for impalpable breast cancer from July 2017 to August 2019. Data recorded included tumour demographics, localisation method, size of tumour and specimen weight. Evaluation of localisation methods included re-excision rates, type of further surgery, cost saving in reduction in re-excision, and patient satisfaction. Result(s): 2017/2018 226 Traditional guided WLE were performed. 2018/2019 90 traditional guided WLE, and 106 Magseed WLE were performed. Tumour demographics, size of tumour were similar for localisation methods. The introduction of Magseed in our practice has resulted in a significant reduction in overall re-excision rates from 22.4 to 12%, (z =2.6616 p.00782), and average specimen weight from 40 to 27g (t= -3.2364, P.000716). Cost saving analysis of further surgery showed a saving of 34,457 with 48% less further operations following change of practice. 98% of patients had a very good/excellent experience of Magseed. Conclusion(s): Magseed demonstrates a triple effect on patient outcome with significant reduction in re-excision rate, cost saving by reducing further surgery and high patient satisfaction.

The histopathological correlation of magnetic resonance imaging-identified additional lesions detected in 2nd read breast MRIS (2020)

Posted on by

Type of publication:
Conference abstract

Author(s):
*Aksoy U.; *Barlow E.; *Williams S.; *Lake B.; *Metelko M

Citation:
European Journal of Surgical Oncology; Jun 2020; vol. 46 (no. 6), p. e19

Abstract:
Introduction: Magnetic resonance imaging-identified additional lesions (MRALs) in breast cancer have always been a diagnostic dilemma as they may result in significant delay in management plans and sometimes cause overtreatment. Clinical guidelines for the management of breast cancer in the UK recommend second read MRIs in at least 50% of patients. In this audit project, our aim is to correlate the MRALs reported in 2nd read breast MRIs (2bMRI) with the histopathological outcomes.
Method(s): The patients who were referred to 2bMRIs between July 2018 and August 2019 were retrieved from the archives. 86 consecutive patients (mean age: 54) were included in the audit. First read MRIs were correlated with 2bMRI results and noted as; agreed, a larger lesion (>1cm) or additional foci reported, a smaller lesion or fewer number of additional foci reported. According to histopathology reports MRALs were classified as; proved malignant, benign or not applicable.
Result(s): In 80% (69/86) of the patients the 2bMRI reports agreed with the first and the management did not change. In 20% there was disagreement. Five true positive cases benefited from more extensive surgery. Eight false positive cases ended up with more extensive surgery.
Conclusion(s): Referral indications were in accordance with the guidelines and 5.8% of the patients benefited from the 2bMRIs. However, a significant number of the patients did not benefit from the 2bMRIs. Larger studies are needed to see the true benefit of 2bMRIs as they have the potential to delay the patient pathway and increase anxiety levels of breast cancer patients.

Routine Use of Swallowing Outcome Measures Following Head and Neck Cancer in a Multidisciplinary Clinic Setting (2021)

Posted on by

Type of publication:
Journal article

Author(s):
*Annette C. Zuydam, Simon N. Rogers, Kate Grayson, *Clare F. Probert

Citation:
International Archives of Otorhinolaryngology, 2021; 25(02): e185-e192

Abstract:
Introduction: Chemoradiotherapy treatment for head and neck cancer (HNC) can have a major impact on swallowing function and health-related quality of life. The use of outcome measures in early detection of patients with swallowing problems provides the opportunity for targeting speech and language therapy (SLT) interventions to aid adaption and promote better clinical outcomes.
Objective: The purpose of the present study was to assess relationships between four outcomes measures over time, in a cohort of HNC patients, treated by (chemo-) radiotherapy.
Methods: Data were collected at 3 months and 12 months, on 49 consecutive patients with primary squamous cell cancer of the oropharynx, nasopharynx or hypopharynx stage T1–4, N0–2b, M0 disease.
Results: Out of 49 eligible patients, 45 completed assessment at 3 months and 20 at 12 months. The 3-month outcomes gave a strong indication of performance at 1 year. There were several strong correlations found between measures. The strongest was between the 3-month Performance Status Scale for Head and Neck Cancer (PSSHN) and the 12-month PSSHN (rs ¼ 0.761, n ¼ 17), the 12-month PSSHN and the 12-month
Functional Oral Intake Scale (FOIS) (rs ¼ 0.823, n ¼ 20), and the 12-month University of Washington Head and Neck Quality of Life (UWQoL) swallow and the 12-month Water Swallow Test (WST) capacity (rs ¼ 0.759, n ¼ 17).
Conclusion: The UW-QoL swallow item and WST are easy to incorporate into routine care and should be used as part of a standard assessment of swallow outcome. These measures can serve to help screen patients for dysfunction and focus allocation of resources for those who would benefit from more comprehensive assessment and intervention by SLT.

Link to full-text [open access - no password required]

Transanal endoscopic microsurgery for early rectal cancer-can it be done safely with good outcomes at a in a UK district general hospital (2019)

Posted on by

Type of publication:
Conference abstract

Author(s):
*Vidyasankar V.; *Chakrabarthy A.; *McCloud J.; *Clarke R.

Citation:
Colorectal Disease; Sep 2019; vol. 21, S3, p. 54

Abstract:
Aim: Randomised controlled trials have demonstrated advantages of Transanal endoscopic microsurgery (TEMS) for early rectal cancer resections. The aim of our study was to assess the safety and outcome of TEMS for early rectal cancer at a U.K district general hospital. Method(s): Between July 2011 to January 2017, 27 patients, 13 men and 14 women, Mean age 77 years, underwent TEMS. Mean lesion diameter was 49 mm. Patient selection was based on multidisciplinary decision. Follow up included colonoscopy, MRI and CT according to standard protocol. Patients were admitted for overnight observation and discharged the following day. Result(s): Mean operative time was 60 minutes. Average hospital stay was 24 hours. One patient (3.7%) had bleeding, three (11%) developed perforation, which were identified and repaired immediately. Two (7.4%) developed pyrexia, One patient (3.7%) developed minor stricture. One (3.7%) developed a recto-vaginal fistula. R0 resection was achieved in 81% and R1 resection was achieved in 19% of cancer cases. One patient (3.7%) developed local recurrence. No mortality. Conclusion(s): Our study demonstrates that TEMS for early rectal cancer can be safely performed in selected patients at a district general hospital, with outcomes comparable with international data.

Link to full-text [no password required]

Magseed for Localisation of Impalpable Breast Cancer is associated with High Patient Satisfaction and Lower Re-excision Rates (2019)

Posted on by

Type of publication:
Poster presentation

Author(s):
*L.Deane, *B.Lake, *M.Wilson, *S.Williams, *M.Metelko, *G.Thomas, *S.Lewis, *L.Norwood, *T.Usman

Citation:
Poster presented at the International Cambridge Conference on Breast Cancer Imaging, July 2019

Link to poster [PDF]

Elevated BMI Significantly increases recurrence rate of Breast Cancer; a district general hospital experience (2019)

Posted on by

Type of publication:
Poster presentation

Author(s):
*Blossom Lake, *Albert Mansoor, *Donna Appleton

Citation:
British Journal Surgery; September 2019; Vol 106(S5), p.20 (Poster presentation at Association of Surgeons of Great Britain May 2019)

Abstract:
Aims: Excess body weight has been shown to be a risk factor for breast cancer recurrence. The aim of this study was to evaluate the effect of BMI on recurrence rate of Breast cancer in Shropshire.
Methods: Retrospective analysis of Somerset Database of all new breast cancers diagnosed from January 2012 to December 2012 at the Shrewsbury & Telford NHS Trust. Clinical portal and pre-op database were used to obtain patient demographics including BMI and recurrence rate. Excluded patients from analysis: no surgery performed, or operated at another hospital. Overall recurrence rate, local recurrence, distant metastasis rate and 5 year disease free survival (DFS) were compared for 3 groups: BMI< 25, overweight; 25.1-29.9,and obese; >30.
Results: 498 new breast cancers were diagnosed in 2012, of these 132 were excluded as per criteria. 366 records were analysed; 40 patients had recurrent breast cancer 10.9%. 97.5% of recurrent patients had one or more prognostic factor, size> 3cm, node positive or Grade 3, with no significant difference between BMI groups for adverse prognostic factors. Overall Recurrence rate for BMI <25 was 5.9%, this was significantly higher in BMI> 25, 13.3% p<0.05.BMI Overall Recurrence rate Local recurrence Distant Metastasis rate 5 year DFS<25 5.9% 0.8% 5.9% 94.1% Overweight 14.4% 4.2% 10.2% 85.6% Obese 12.3% 2.3% 11.5% 87.7%
Conclusion: Our experience suggests a significant increase in Breast Cancer recurrence with increasing BMI. Further studies are needed to clarify this and whether methods of reducing BMI may improve disease free survival

Link to full-text [no password required]

Optimizing chemotherapy for frail and/or elderly patient with advanced gastroesophageal cancer (AGOAC): the GO2 phase III trial (2019)

Posted on by

Type of publication:
Conference abstract

Author(s):
Swinson D.E.; Hall P.; Seymour M.; Lord S.; Marshall H.; Ruddock S.; Cairns D.; Waters J.; Wadsley J.; Falk S.; Roy R.; Joseph M.; Nicoll J.; Vellios Kamposioras K.; Tillett T.; Cummins S.; Grumett S.; Stokes Z.; Waddell T.; *Chatterjee A.; Garcia A.; Allmark C.; Khan M.; Petty R.

Citation:
Journal of Geriatric Oncology; Nov 2019; vol. 10 (no. 6), Supplement 1, S8

Abstract:
Introduction: aGOAC patients are frequently elderly and/or frail.
Objective(s): (i) find the optimum dose of oxaliplatin capecitabine (OCap) for this population; (ii) explore the use of an objective geriatric assessment to individualize dose for maximum overall treatment utility (OTU), a composite of clinical benefit, tolerability, quality of life (QL) and patient value.
Method(s): Patients with aGOAC were eligible if there was uncertainty of the appropriate dose of chemotherapy. Baseline assessment included global QL; symptoms; functional scales; comorbidity; frailty. Randomization was 1:1:1 to dose Level A (Ox 130 mg/m2 d1, Cap 625 mg/m2 bd d1-21, q21d), B (80% Level A) or C (60% Level A). At 9 weeks, patients were scored for OTU. Non-inferiority (vs A) was assessed using PFS, censored at 12 months, with upper boundary HR 1.34 (based on patients' and clinicians' discussions), needing 284 PFS events per two-way comparison. In a separate sub-study, when there was uncertainty regarding the use of chemotherapy, patients were randomized between level C and supportive care alone (SCA).
Results and Conclusion(s): 512 patients were randomized, 2014-2017, at 61 UK centers. Age, performance status and frailty were similar in all arms. Non-inferiority of PFS is confirmed for Level B vs A (HR 1.09, CI 0.89-1.32) and for Level C vs A (HR 1.10, CI 0.90-1.33). Level C patients had the least toxicity and best OTU outcomes. When analyzed by baseline age, frailty and PS no group was identified who benefit more from higher treatment doses. A further 46 patients were randomized between chemotherapy and SCA. A non-significant trend to improved survival was observed (HR=0.69, CI 0.32-1.48) and QL deteriorated less with chemotherapy. This is the largest RCT specifically investigating frail and/or elderly aGOAC patients, and should guide future treatment. The lowest dose tested was non-inferior in terms of PFS, produced less toxicity and better overall treatment utility.

Will Weekly Win for Taxol in the UK: Comparison of Outcomes in Metastatic and locally advanced breast cancer with weekly vs. 3 weekly administration of paclitaxel: A randomised two-arm, prospective, multi-centre, open-label phase III trial comparing the activity and safety of a weekly versus a three-weekly paclitaxel treatment schedule in patients with advanced or metastatic breast cancer (2019)

Posted on by

Type of publication:
Randomised controlled trial

Author(s):
Cameron, D. and Verrill, M.

35 patients from Shrewsbury and Telford Hospital NHS Trust were involved in this trial.

Citation:
Unpublished final report

Abstract:
Background: Paclitaxel has significant anti-tumour activity in patients with metastatic breast cancer who either relapse after, or are resistant, to anthracycline based treatment. In this setting, paclitaxel was routinely given as a 3-hour IV infusion at a dose of 175 mg/m2 every 3 weeks. With the aim of optimising dose and schedule of paclitaxel for patients with metastatic breast cancer, a weekly, dose-dense regimen was developed and used in various settings.
Patients and Methods: A total of 569 patients were recruited into the trial – the first and last patients were randomised on 16 September 2002 and 31 July 2006 respectively. The 2 arms were well balanced for sites of metastases, extent of prior radiotherapy and chemotherapy. The median follow up at May 2012 (when the final analysis was performed) was 94 months = 7 years, 10 months.
Results: Response rates for the weekly regimen were significantly higher than the 3-weekly arm (chi-squared test of association: p = 0.002; responses were weekly CR 3.2%, PR 18.3% vs. 3-weekly CR 1.7% and PR 11.3%). There was no significant difference in either time to progression (log rank test: p = 0.127) or overall survival (log rank test: p = 0.193) between the 2 arms.
Conclusions: In this randomised controlled trial of best scheduling, weekly paclitaxel showed a statistically higher objective response activity compared to 3-weekly schedule but no survival benefit was seen.