Proton Versus Photon Therapy in Anal Squamous Cell Carcinoma
- Conditions
- Anal Cancer Squamous Cell
- Interventions
- Radiation: Photon radiotherapyRadiation: Proton radiotherapy
- Registration Number
- NCT04462042
- Lead Sponsor
- Umeå University
- Brief Summary
Dosimetric studies suggest that radiotherapy with protons has a potential to reduce side effects compared to treatment with photons for patients with anal carcinoma (AC). There are so far no studies comparing these treatment techniques in a randomised setting. The aim of this study is to compare side effects following photon therapy versus proton therapy within the framework of a randomised controlled trial.
- Detailed Description
Anal carcinoma is a disease in which modern therapy is reasonably successful in achieving tumour control/cure. Both acute and late side effects are substantial. Proton radiotherapy is hypothesised to have the potential to decrease the incidence/severity of some acute side effects from certain organs at risk e.g. bone marrow and intraperitoneal bowel. By sparing the dose to these organs it is also possible that late effects might be less evident. Sparing of the bone marrow may lead to fewer septic events and dose reductions of chemotherapy which may, as a consequence, improve tumour control. The primary aim of this study is to find ways to decrease acute side effects primarily to alleviate some discomfort from the patient during and after a usually painful treatment experience. It has also been concluded by others that reduction of acute side effects is a relevant aim and end point for the evaluation of new treatment techniques and both patient reported and physician reported data are assessed
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
- The patient must be at least 18 years old
- Histologically confirmed, previously untreated squamous cell carcinoma (p16-positive or p16-negative) of the anal canal (ICD-O-3 C21), i.e. cancer of the perianal skin without connection to the anal canal are not included. The patients may have primary tumour, regional nodes, metastasis (TNM)-stage T2 (>4 cm) -4,N0-1c,M0 (UICC 8th edition).
- World Health Organisation/Eastern Cooperative Oncology Group (WHO/ECOG) performance status 0-1
- The patient must be able to understand the information about the treatment and give a written informed consent.
- Patients with cancer of the perianal skin without involvement of the anal canal (ICD-O-3 C44.5) are not eligible.
- Patient judged to have any other treatment than radiotherapy with concomitant chemotherapy as the preferred treatment
- Concomitant or previous malignancies. Exceptions are, adequately treated basal cell carcinoma or squamous cell carcinoma of the skin or, other previous malignancy with a disease-free interval of at least 5 years.
- Two or more synchronous primary cancers in the pelvic region at time of diagnosis
- Previous radiotherapy, surgery or chemotherapy that may interfere with the planned treatment for the present disease, as judged by the investigator.
- Co-existing disease prejudicing survival (expected survival should be >2 years).
- Pregnancy or breast feeding
- When prosthetic materials (e.g. hip prostheses) are present close to the target volume it must be considered if this may introduce uncertainties in dose calculations that precludes especially, proton therapy.
- Patients with pacemaker/ICD are not eligible.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Photon radiotherapy Photon radiotherapy Conventional photon radiation is delivered by volumetric arc therapy/intensity modulated radiotherapy/helical tomotherapy using simultaneous integrated boost (SIB) technique. The total dose to the primary tumour target and node metastases \>2 cm is 57.5 Gy in 27 fractions, one fraction/day, five fractions/week during 5.5 weeks. Node metastases up to 2 cm will receive 50.5 Gy in 27 fractions. Elective lymph nodes will receive a total dose of 41.6 Gy. Proton radiotherapy Proton radiotherapy Proton radiation is delivered by spot scanning. Proton plans will be produced by single field optimisation/single field uniform dose or multifield optimisation/intensity modulated proton therapy using simultaneous integrated boost (SIB) technique. The total dose to the primary tumour target and node metastases \>2 cm is 57.5 Gy(RBE) in 27 fractions, one fraction/day, five fractions/week during 5.5 weeks. Node metastases up to 2 cm will receive 50.5 Gy(RBE) in 27 fractions. Elective lymph nodes will receive a total dose of 41.6 Gy(RBE).
- Primary Outcome Measures
Name Time Method Acute grade >2 hematological side effects Treatment start until three months after treatment Acute hematological side effects will be assessed by weekly full blood cell counts during radiotherapy and the first three weeks after treatment completion. Side Grade \>2 acute GI and haematological side-effects during therapy and up to three weeks after the end of treatment. Thereafter, every six weeks for up to three months after treatment. Results will be graded according to the Common Terminology Criteria for Adverse Events (NTCAE) v5.0 scoring system.
Haematological adverse events will also be assessed by registering febrile episodes during an after treatment as well as the frequency of chemotherapy dose reduction or delayed chemotherapy.
- Secondary Outcome Measures
Name Time Method Locoregional failure Up to five years after randomisation Time from randomisation until first recurrence, local and/or regional
Overall survival Up to five years after randomisation Time from randomisation until death
Acute side effects from skin Treatment start until three months after treatment Acute side-effects from skin are assessed by using the Common Terminology Criteria for Adverse Events (NTCAE) v5.0 scoring system. Patient reported side effects are assessed by the European Organization for Research and Treatment of Cancer (EORTC), disease specific questionnaire, QLQ-ANL27.
During radiotherapy, daily reported symptoms will be investigated by a newly developed symptom scale, Radiotherapy related symptom assessment scale (RSAS). The questionnaire includes 13 items specific for current diagnose. The RSAS is a validated instrument for assessing symptom intensity and distress in patients with different cancer disease undergoing radiotherapy, with psychometric properties within the expected range. Answering categories ranges from not at all to a great deal (1-4).Late side effects from the gastro-intestinal system From three months after treatment up to five years after treatment Late side effects 1, 2 and 5 years after completion of treatment. Side effects from the gastrointestinal system, are assessed by using the NTCAE v5.0 scoring system. Patient reported side effects are assessed by the EORTCs disease specific questionnaire, QLQ-ANL27.
Late side effects from skin From three months after treatment up to five years after treatment Late side effects 1, 2 and 5 years after completion of treatment. Side effects from the skin are assessed by using the NTCAE v5.0 scoring system. Patient reported side effects are assessed by the EORTCs disease specific questionnaire, QLQ-ANL27.
Assessment of Quality of life (QoL) From randomisation up to 5 years Patient reported quality of life during and after treatment assessed by • HRQoL will be investigated with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire, the QLQ-C30, supplemented by the disease specific module (anal-cancer) QLQ-ANL27. • EuroQol (EQ-5D) is a generic QoL instrument designed for self-administration. The result could be expressed as a weight with values between zero and one (0-1). Together with information about survival the QoL weight can be expressed as quality-adjusted life-years (QALYs).
Pain due to acute radiation reaction Treatment start until three months after treatment Pain is assessed by using the NTCAE v5.0 scoring system. Patient reported pain is assessed by the European Organization for Research and Treatment of Cancer (EORTC), disease specific questionnaire, QLQ-ANL27.
During radiotherapy, daily reported symptoms will be investigated by a newly developed symptom scale, Radiotherapy related symptom assessment scale (RSAS). The questionnaire includes 13 items specific for current diagnose. The RSAS is a validated instrument for assessing symptom intensity and distress in patients with different cancer disease undergoing radiotherapy, with psychometric properties within the expected range. Answering categories ranges from not at all to a great deal (1-4).Late side effects From three months after treatment up to five years after treatment Late side effects 1, 2 and 5 years after completion of treatment. Side effects from the genitourinary system are assessed by using the NTCAE v5.0 scoring system. Patient reported side effects are assessed by the EORTCs disease specific questionnaire, QLQ-ANL27.
Acute grade >2 gastrointestinal side effects Treatment start until three months after treatment Acute side-effects from the gastrointestinal tract are assess the NTCAE v5.0 scoring system by using. Patient reported side effects are assessed by the European Organization for Research and Treatment of Cancer (EORTC), disease specific quality of life questionnaire for anal cancer, (QLQ-ANL27).
During radiotherapy, daily reported symptoms will be investigated by a newly developed symptom scale, Radiotherapy related symptom assessment scale (RSAS). The questionnaire includes 13 items specific for current diagnose. The RSAS is a validated instrument for assessing symptom intensity and distress in patients with different cancer disease undergoing radiotherapy, with psychometric properties within the expected range. Answering categories ranges from not at all to a great deal (1-4).Acute side effects from the genitourinary tract Treatment start until three months after treatment Acute side-effects from the genitourinary tract are assessed by scoring of genitourinary symptoms, pain by using the Common Terminology Criteria for Adverse Events (NTCAE) v5.0 scoring system. Patient reported side effects are assessed by the European Organization for Research and Treatment of Cancer (EORTC), disease specific questionnaire, QLQ-ANL27.
During radiotherapy, daily reported symptoms will be investigated by a newly developed symptom scale, Radiotherapy related symptom assessment scale (RSAS). The questionnaire includes 13 items specific for current diagnose. The RSAS is a validated instrument for assessing symptom intensity and distress in patients with different cancer disease undergoing radiotherapy, with psychometric properties within the expected range. Answering categories ranges from not at all to a great deal (1-4).Primary tumour response 3-6 months after treatment Frequency of complete tumour regression after primary treatment
Disease free survival Up to five years after randomisation Time from randomisation until first recurrence, local/regional/systemic or death
Trial Locations
- Locations (4)
Sahlgrenska University Hospital
🇸🇪Göteborg, Sweden
Lund University Hospital
🇸🇪Lund, Sweden
Umeå University Hospital
🇸🇪Umeå, Sweden
Uppsala University Hospital
🇸🇪Uppsala, Sweden