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    Appendix B: Other relevant studies

    Other potentially relevant studies that were not included in the main evidence summary (tables 2 and 3) are listed in table 5 below.

    Table 5. Additional studies identified

    Study

    Number of people and follow-up

    Direction of conclusions

    Reason study was not included in main evidence summary

    Baker A, Buckley L, Misra V, Bridge P. (2019) Clinical audit of rectal cancer patient referrals for Papillon contact brachy-therapy. Journal of Radio-therapy in Practice. 19: 321-326.

    Audit of referral patterns between 2013 - 2019

    N=31 patients referred for CXB treatment from a major cancer centre

    cCR for the audit cohort was 93.6%

    Larger and more relevant studies included in the summary of the key evidence.

    Benezery K, Montagne L, Evesque L, Schiappa R, Hannoun-Levi JM, Francois E, Thamphya B, Gerard JP. (2020) Clinical response assessment after contact X-Ray brachytherapy and chemoradiotherapy for organ preservation in rectal cancer T2-T3 M0: The time/dose factor influence. Clinical and Translational Radiation Oncology. 24: 92-98.

    Retrospective case series

    N=61 people with T2-3 rectal adenocarcinoma (40 people whose cancer was treated with CXB first and 21 with EBRT first [if the tumour exceeded 3.5 cm])

    Median follow-up 61 months

    At 6 months, with CXB first all people were in cCR; five with EBRT remained in partial response. The local recurrence rate was 10% (6 to 16) at 5 years. T3 and fungating tumours were at higher risk of local recurrence. Organ preservation with good function was achieved in 95% of cases

    Larger and more relevant studies included in the summary of the key evidence.

    Bennett H, Rao C, Batten L, Hasler E, Jarrom D, Prettyjohns M, Barrington C, Sun Myint A. (2024) Low energy contact X-ray brachytherapy for treatment of rectal cancer: a health technology appraisal by Health Technology Wales. Colorectal Disease. 26:1053-1058.

    Cost-effectiveness analysis

    In Wales, CXB was cost effective compared with external-beam boost at a cost of £4,463 per quality-adjusted life year gained.

    CXB was estimated to provide 0.2 quality-adjusted life years at an additional cost of £887 per person.

    The focus of the study is on cost-effectiveness, which is outside the remit of IP guidance.

    Clements E, Kinsella J, Rao C, Myint AS. [AIC]. Exploring Patient Experiences and Quality of Life Following Low Energy Contact X-ray Brachytherapy (Papillon) Treatment for Rectal Cancer: A Thematic Analysis. [unpublished AIC]

    Thematic analysis of free-text data from a population-based National Institute of Clinical Excellence (NICE) administered survey.

    N=61

    108 comments analysed

    Despite experiencing side effects, patients would recommend this procedure to others, emphasizing the avoidance of major radical surgical resection and stoma formation

    Have included QoL and PROM data from a more robust source.

    Custers PA, Geubels BM, Huibregtse IL, Peters FP, Engelhardt EG, Beets GL, Marijnen CAM, van Leerdam ME, van Triest B. (2021) Contact X-ray Brachytherapy for Older or Inoperable Rectal Cancer Patients: Short-Term Oncological and Functional Follow-Up. Cancers. 13: 6333.

    Prospective cohort study

    N=19

    Median follow-up 13 months (range 6 to 32 months)

    Nine people achieved a cCR and 4 achieved local control of the tumor. The 12-month organ-preservation rate, PFS, and OS were 88%, 78%, and 100%, respectively. A transient decrease in quality of life and bowel function was observed at 3 months, which was generally restored at 6 months

    Larger and more relevant studies included in the summary of the key evidence.

    Custers PA, Maas M, Lambregts DMJ, Beets-Tan RGH, Beets GL, Peters FP, Marijnen CAM, van Leerdam ME, Huibregtse IL, van Triest B. (2022) Features on Endoscopy and MRI after Treatment with Contact X-ray Brachytherapy for Rectal Cancer: Explorative Results. Cancers. 14: 5565.

    Prospective cohort study

    N=36

    Median follow-up 14 (2 to 43) months

    No outcomes of interest reported

    No outcomes of interest reported.

    Dhadda AS, Martin A, Killeen S, Hunter IA. (2017) Organ Preservation Using Contact Radio-therapy for Early Rectal Cancer: Outcomes of Patients Treated at a Single Centre in the UK. Clinical Oncology. 29: 198-204.

    Prospective cohort study

    N=42

    Median follow-up 24 (5 to 54) months

    Local recurrence free survival after CXB: 88%

    Disease free survival after CXB: 86%

    Overall survival after CXB: 88% with a median follow-up of 24 months.

    The LARS score for patient who were organ preserved revealed that 65% of all people retained reasonable to good bowel function (LARS score 0 to 20).

    Satisfaction with treatment: 92% (39 out of 42)

    Larger and more relevant studies included in the summary of the key evidence.

    Dunstan MJD, Rockall TA, Potter K, Stewart AJ. (2018) Radiological and clinical findings following rectal contact X-ray brachytherapy (Papillon technique) - how to assess response. Journal of Contemporary Brachytherapy. 10: 179-189.

    Case series

    N=7

    No outcomes of interest reported

    No outcomes of interest reported.

    Frin AC, Evesque L, Gal J, Benezery K, François E, Gugenheim J, Benizri E, Château Y, Marcié S, Doyen J, Gérard JP. (2017) Organ or sphincter preservation for rectal cancer. The role of contact X-ray brachytherapy in a monocentric series of 112 patients. European Journal of Cancer. 72: 124-136.

    Observational study

    N=112 people with rectal adenocarcinoma treated with CXB; Group 1 (n=27): T1N0 tumours less than 3 cm treated with initial local excision; Group 2 (n=45): T2 or early T3, N0 (less than 4 cm) treated with CXB plus CRT or EBRT; Group 3 (n=40): distal locally advanced T3N0-2 treated with neoadjuvant CXB plus CRT or EBRT

    Median follow-up: Group 1: 63 months; group 2: 60 months; group 3: 40 months

    Group 1: Organ preservation was achieved in 26 people (96%). Group 2: cCR was observed in 43 out of 45 (96%) of people and 3 people developed a local recurrence (11% at 5 years). The specific survival was 76% at 5 years and the rate of organ preservation was 89% (40 out of 45) with good bowel function in 36 people.
    Group 3: Anterior resection (with sphincter preservation) was possible in 35 people (86%) with a 3-year local recurrence of 6%

    Larger and more relevant studies included in the summary of the key evidence.

    Gerard JP, Frin AC, Doyen J, Zhou FX, Gal J, Romestaing P, Barbet N, Coquard R, Chapet O, François E, Marcié S, Benezery K. (2015) Organ preservation in rectal adeno-carcinoma (T1) T2-T3 Nx M0. Historical overview of the Lyon Sud - Nice experience using contact x-ray brachytherapy and external beam radiotherapy for 120 patients. Acta Oncologica. 54: 545-551.

    Retrospective cohort study

    N=120 people with stage T1 to T3 rectal cancer treated by low-energy CXB and EBRT

    Median follow-up 5.2 years

    People who had CXB achieved a high rate of cCR. Rate of local recurrence at 5 years was 14 to 27%. The most frequent toxicity was rectal bleeding

    Larger and more relevant studies included in the summary of the key evidence.

    Lavertu S, Schild SE, Gunderson LL, Haddock MG, Martenson JA. (2003) Endocavitary radiation therapy for rectal adeno-carcinoma: 10-year results. American Journal of Clinical Oncology. 26: 508-512.

    Retrospective cohort study

    N=35

    Median follow-up 102 (range from 7 to 163) months

    For people treated with curative intent, the survival rate was 65% at 5 years and 42% at 10 years. Median survival for these people was 67 months. One of the 6 people treated palliatively was alive 56 months

    Larger and more relevant studies included in the summary of the key evidence.

    Picardi C, Caparrotti F, Montemurro M, Christen D, Schaub NB, Fargier-Voiron M, Lestrade L, Meyer J, Meurette G, Liot E, Helbling D, Schmidt J, Gutz-willer JP, Bernardi M, Matzinger O, Ris F. (2024) High Rates of Organ Preservation in Rectal Cancer with Papillon Contact X-ray Radiotherapy: Results from a Swiss Cohort. Cancers. 16: 2318.

    Retrospective cohort study

    N=24 people with rectal cancer and a minimum follow-up of 12 months, treated with a CXB boost, with or without chemotherapy

    Median follow-up 43 months

    The organ preservation rate was 96% (23 out of 24), and the local relapse rate was 8% (2 out of 24). No people developed grade 3 or higher toxicities

    Larger and more relevant studies included in the summary of the key evidence.

    Rao C, Stewart A, Martin AP, Collins B, Pritchard DM, Athanasiou T, Sun Myint A. (2018) Contact X-ray Brachytherapy as an Adjunct to a Watch and Wait Approach is an Affordable Alternative to Standard Surgical Management of Rectal Cancer for Patients with a Partial Clinical Response to Chemoradiotherapy. Clinical Oncology. 30: 625-633.

    Budget impact analysis and cost-consequence analysis

    A watch-and-wait policy with a CXB boost is less costly than standard surgical management.

    The technology would become cost saving within 5 years.

    In all scenarios, the cumulative cost of implementation of the intervention fell below the NICE threshold

    No relevant outcomes reported.

    Smith FM, Al-Amin A, Wright A, Berry J, Nicoll JJ, Sun Myint A. (2016) Contact radiotherapy boost in association with 'watch and wait' for rectal cancer: initial experience and outcomes from a shared programme between a district general hospital network and a regional oncology centre. Colorectal Disease. 18: 861-870.

    Retrospective cohort study

    N=17

    Median follow-up 20 (5 to 54) months

    Of the 14 patients who remain alive, 11 (79%) have a sustained complete (n=8) or partial (n=3) response

    Larger and more relevant studies included in the summary of the key evidence.

    Smith FM, Pritchard DM, Wong H, Whitmarsh K, Hershman MJ, Sun Myint A. (2019) A cohort study of local excision followed by adjuvant therapy incorporating a contact X-ray brachytherapy boost instead of radical resection in 180 patients with rectal cancer. Colorectal Disease. 21: 663-670.

    Cohort study

    N=180 people who had local excision

    pT1 = 131 (72%),

    pT2 = 44 (26%),

    pT3 = 5 (2%).

    110 people also had chemo-radiotherapy and 60 had radiotherapy alone.

    Median follow-up 36 (6 to 48) months

    At a median follow-up of 36 months 169 people (94%) remained free of local recurrence. Of the 11 patients with local recurrence (3 isolated nodal), 5 underwent salvage abdominoperineal excision. 8 people developed distant disease, of whom 5 underwent meta-stasis surgery. At last follow-up, 173 (96%) people were free of all disease and 170 (94%) were stoma free

    The study population likely overlaps with that of a larger and more recent study included in the key evidence.

    Sun Myint A, Grieve RJ, McDonald AC, Levine EL, Ramani S, Perkins K, Wong H, Makin CA, Hershman MJ. (2007) Combined modality treatment of early rectal cancer: the UK experience. Clinical Oncology. 19: 674-681.

    Retrospective cohort study

    N=220

    Median follow-up 4.6 (0.25 to 11.25) years

    124 of 220 people had CXB. There were 24 out of 220 people (11%) with residual disease after initial radiotherapy. 21 people (87.5%) had immediate rescue surgery. There were 22 people with late recurrences (10%) and 11 people had local recurrence alone

    Larger and more relevant studies included in the summary of the key evidence. The study population likely overlaps with those of larger and more recent studies included in the key evidence.

    Sun Myint A, Smith FM, Gollins S, Wong H, Rao C, Whitmarsh K, Sripadam R, Rooney P, Hershman M, Pritchard DM. (2018) Dose Escalation Using CXB After External Beam Radiotherapy as Nonsurgical Treatment Option for Rectal Cancer: Outcomes From a Single-Center Experience. International Journal of Radiation Oncology Biology Physics. 100: 565-573.

    Retrospective cohort study

    N=83

    Median follow-up 2.5 (1.2 to 8.3) years

    cCR was achieved in 53 people (63.8%) after CXB boost; among these, 7 people (13.2%) developed a relapse; the 6 people (11.6%) with nonmetastatic regrowth underwent salvage surgery. At the end of the study period, 69 of 83 people (83.1%) were cancer free

    Larger and more relevant studies included in the summary of the key evidence.

    Sun Myint A, Rao C, Barbet N, Thamphya B, Pace-Loscos T, Schiappa R, Magné N, Martel-Lafay I, Mineur L, Deberne M, Zilli T, Dhadda A., Gerard JP. (2023) The safety and efficacy of total mesorectal excision (TME) surgery following dose-escalation: Surgical outcomes from the organ preservation in early rectal adenocarcinoma (OPERA) trial, a European multicentre phase 3 randomised trial. Colorectal Disease. 25: 2160-2169.

    RCT

    N=148

    Median follow-up 38.2 months

    Whilst there was a statistically significant decrease in the TME rate following CXB boost (HR 0.38, 95% CI 0.19 to 0.74, p = 0.00419) there was no difference in surgical outcomes between patients who had EBRT and CXB boost

    Study reporting later follow-up included in the key evidence summary.