Use of a non-endoscopic immunocytological device (Cytosponge™) for post chemoradiotherapy surveillance in patients with oesophageal cancer in the UK (CYTOFLOC): A multicentre feasibility study.

Background: Effective surveillance strategies are required for patients diagnosed with oesophageal squamous cell carcinoma (OSCC) or adenocarcinoma (OAC) for whom chemoradiotherapy (CRT) is used as a potentially-curative, organ-sparing, alternative to surgery. In this study, we evaluated the safety, acceptability and tolerability of a non-endoscopic immunocytological device (the Cytosponge™) to assess treatment response following CRT. Methods: This multicentre, single-arm feasibility trial took place in 10 tertiary cancer centres in the UK. Patients aged at least 16 years diagnosed with OSCC or OAC, and who were within 4-16 weeks of completing definitive or neo-adjuvant CRT, were included. Participants were required to have a Mellow-Pinkas dysphagia score of 0-2 and be able to swallow tablets. All patients underwent a single Cytosponge™ assessment in addition to standard of care (which included post-treatment endoscopic evaluation with biopsy for patients undergoing definitive CRT; surgery for those who received neo-adjuvant CRT). The primary outcome was the proportion of consented, evaluable patients who successfully underwent Cytosponge™ assessment. Secondary and tertiary outcomes included safety, study consent rate, acceptance rate, the suitability of obtained samples for biomarker analysis, and the comparative efficacy of Cytosponge™ to standard histology (endoscopy and biopsy or post-resection specimen) in assessing for residual disease. The trial is registered with ClinicalTrials.gov, NCT03529669. Findings: Between 18th April 2018 and 16th January 2020, 41 (42.7%; 95% confidence interval (CI) 32.7-53.2) of 96 potentially eligible patients consented to participate. Thirty-nine (95.1%, 95% CI 83.5-99.4) successfully carried out the Cytosponge™ procedure. Of these, 37 (95%) would be prepared to repeat the procedure. There were only two grade 1 adverse events attributed to use of the Cytosponge™. Thirty-five (90%) of the completed Cytosponge™ samples were suitable for biomarker analysis; 29 (83%) of these were concordant with endoscopic biopsies, three (9%) had findings suggestive of residual cancer on Cytosponge™ not found on endoscopic biopsies, and three (9%) had residual cancer on endoscopic biopsies not detected by Cytosponge™. Interpretation: Use of the CytospongeTM is safe, tolerable, and acceptable for the assessment of treatment response following CRT in OAC and OSCC. Further evaluation of Cytosponge™ in this setting is warranted. Funding: Cancer Research UK, National Institute for Health Research, Medical Research Council.

Management of the axilla following neoadjuvant chemotherapy for breast cancer- A change in practice.

OBJECTIVES: Chemotherapy in the neo adjuvant setting has allowed downsizing of breast tumours thus allowing patients to benefit from breast conservation surgery. The effect of neoadjuvant chemotherapy (NAC) has also been observed in the axilla but most units are still treating the axilla with axillary lymph node dissection (ALND). MATERIALS AND METHODS: A prospective database of breast cancer patients receiving NAC between 2007 and 2016 at a single breast unit was reviewed. The management of the axilla and outcomes was studied. RESULTS: 165 patients received NAC, 123 (74.5%) were clinically/radiologically node positive and 42 were negative. Median age was 50 years. 26.7% had triple negative disease and 34.5% were HER2 positive. 56/123 (45.5%) patients with positive nodes at the outset responded completely to NAC. 40 patients with positive nodes pre-NAC had post NAC SLNB with 37 requiring adjuvant radiotherapy only. 83/123 went directly to ALND post NAC and of these 27 were node negative and therefore may be considered to have had an unnecessary ALND. Overall mortality was 20.6% (34), local recurrence in the breast or mastectomy scar was 3.6% (6) but there was no recurrence in the axilla (0/165) with a median follow up of 67 months. CONCLUSION: There is no clear evidence for management of the axilla post NAC. We have used best available evidence to change our practice over the years and our results should encourage others to de-escalate treatment of the axilla in line with the recently published multidisciplinary guidance on axillary surgery following neoadjuvant chemotherapy.

Dose Escalation Using Contact X-ray Brachytherapy After External Beam Radiotherapy as Nonsurgical Treatment Option for Rectal Cancer: Outcomes From a Single-Center Experience.

PURPOSE: To review the outcomes of rectal cancer patients treated with a nonsurgical approach using contact x-ray brachytherapy (CXB) when suspicious residual disease (≤3 cm) was present after external beam chemoradiation therapy/radiation therapy (EBCRT/EBRT). METHODS AND MATERIALS: Outcome data for rectal cancer patients referred to our institution from 2003 to 2012 were retrieved from an institutional database. These patients were referred after initial local multidisciplinary team discussion because they were not suitable for, or had refused, surgery. All selected patients received a CXB boost after EBCRT/EBRT. Most patients received a total of 90 Gy of CXB delivered in 3 fractions over 4 weeks. RESULTS: The median follow-up period was 2.5 years (range 1.2-8.3). Of 345 consecutive patients with rectal cancer referred to us, 83 with suspicious residual disease (≤3 cm) after EBCRT/EBRT were identified for a CXB boost. Their median age was 72 years (range 36-87), and 58 (69.9%) were men. The initial tumor stages were cT2 (n = 28) and cT3 (n = 55), and 54.2% were node positive. A clinical complete response (cCR) was achieved in 53 patients (63.8%) after the CXB boost that followed EBCRT/EBRT. Of these 53 patients, 7 (13.2%) developed a relapse after achieving a cCR, and the 6 patients (11.6%) with nonmetastatic regrowth underwent salvage surgery (100%). At the end of the study period, 69 of 83 patients (83.1%) were cancer free. CONCLUSIONS: Our data suggest that a CXB boost for selected patients with suspicious residual disease (≤3 cm) after EBCRT/EBRT can be offered as an alternative to radical surgery. In our series, patients with a sustained cCR had a low rate of local regrowth, and those with nonmetastatic regrowth could be salvaged successfully. This approach could provide an alternative treatment option for elderly or comorbid patients who are not suitable for surgery and those with rectal cancer who wish to avoid surgery.

Dose escalation using contact X-ray brachytherapy (Papillon) for rectal cancer: does it improve the chance of organ preservation?

OBJECTIVE: A watch and wait policy for patients with a clinical complete response (cCR) after external beam chemoradiotherapy (EBCRT) for rectal cancer is an attractive option. However, approximately one-third of tumours will regrow, which requires surgical salvage for cure. We assessed whether contact X-ray brachytherapy (CXB) can improve organ preservation by avoiding surgery for local regrowth. METHODS: From our institutional database, we identified 200 of 573 patients treated by CXB from 2003 to 2012. Median age was 74 years (range 32-94), and 134 (67%) patients were males. Histology was confirmed in all patients and was staged using CT scan, MRI or endorectal ultrasound. All patients received combined CXB and EBCRT, except 17 (8.5%) who had CXB alone. RESULTS: Initial cCR was achieved in 144/200 (72%) patients. 38/56 (68%) patients who had residual tumour received immediate salvage surgery. 16/144 (11%) patients developed local relapse after cCR, and 124/144 (86%) maintained cCR. At median follow up of 2.7 years, 161 (80.5%) patients were free of cancer. The main late toxicity was bleeding (28%). Organ preservation was achieved in 124/200 (62%) patients. CONCLUSION: Our data suggest that CXB can reduce local regrowth to 11% compared with around 30% after EBCRT alone. Organ preservation of 62% achieved was higher than reported in most published watch and wait studies. Advances in knowledge: CXB is a promising treatment option to avoid salvage surgery for local regrowth, which can improve the chance of organ preservation in patients who are not suitable for or refuse surgery.

Skin lesion in axilla: an unusual presentation of invasive lobular carcinoma of breast.

Invasive lobular carcinoma (ILC) of breast is known to present with atypical clinical findings in the breast, making it difficult to diagnose. It is also known to have unusual sites of metastases arising de novo or in patients treated for known ILC. Skin lesion in axilla could be a cutaneous metastasis from ILC or ILC in ectopic breast tissue (EBT). We present two cases with skin lesion in axillas which after excision were surprisingly reported as ILC. On further investigations these were found to be primary in EBT. Though such cases are reported, carcinoma arising from EBT is a very rare presentation and one should be aware of this, when dealing with a skin lesion.

Rectal motion can reduce CTV coverage and increase rectal dose during prostate radiotherapy: A daily cone-beam CT study.

BACKGROUND AND PURPOSE: Daily on-treatment verification cone-beam CT (CBCT) was used to study the effect of rectal motion on clinical target volume (CTV) coverage during prostate radiotherapy. MATERIAL AND METHODS: CBCT scans were acquired from 15 patients immediately after daily treatment. From these images, the rectum was contoured allowing the analysis of rectal volume cross-sectional area (CSA) and the determination of rectal dose. Rectal wall motion was quantified as a surrogate measure of prostate displacement and CTV coverage was subjectively assessed. RESULTS: Rectal volume decreased over the treatment course in 13 patients (P<0.001). Rectal wall regions corresponding to the prostate base displayed the greatest motion; larger displacements were seen in patients with larger rectal planning volumes. CTV coverage was inadequate, at the prostate base only, in 38% of the fractions delivered to 4/7 patients with a large rectum at planning (>100 cm(3)). In patients with small rectum at planning (<50 cm(3)) up to 25% more rectal volume than predicted was included in the high-dose region. CONCLUSIONS: Rectal motion during treatment in prostate cancer patients has implications for CTV coverage and rectal dose. Measures to ensure consistency in daily rectal volume or image-guided strategies should be considered.