Neoplasms

All Conditions

Rare Diseases

Chordoma

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Treatment is performed using 16 x 4 GyE protons

protons

Treatment is performed using 16 x 4 GyE carbon ions

carbon ions

The purpose of this study is to evaluate the safety and feasibility of primary hypofractionated irradiation of sacrococcygeal chordoma with carbon ions or protons using the raster scan technique.

The primary objective of this trial is safety and feasibility of hypofractionated irradiation in patients with sacrococcygeal chordoma using protons or carbon ions in raster scan technique for primary or additive treatment after R2 resection. The evaluation is therefore based on the proportion of treatments without Grade 3-5 toxicity (CTCAE, version 4.0) up to 12 months after treatment and/or discontinuation of the treatment for any reason as primary endpoint. Local-progression free survival, overall survival and quality of life will be analyzed as secondary end points.

Ion Irradiation of Sacrococcygeal Chordoma

Hypofractionated Ion Irradiation (Protons or Carbon Ions) of Sacrococcygeal Chordoma

The evaluation is based on incidence of Grade 3-5 toxicity (NCI-CTC-AE) and/or discontinuation of the treatment for any reason. Endpoint is the proportion of treatments without Grade 3-5 toxicity (NCI-CTC-AE) up to 12 months after treatment and/or discontinuation of the treatment for any reason

local progression free survival (LPFS) is determined from start of treatment until local progression in imaging (\>10% size increase)

Further objectives are overall survival (OS) from date of treatment start until the date of death from any cause assessed up to 12 months

Quality of life (QoL) evaluated with EORTC-QLQ30 questionnaire.

Heidelberg University

Prof. Dr.

Mouth and Tooth Diseases

Carcinoma

Parotid Neoplasms

Salivary Gland Neoplasms

Mouth Neoplasms

Head and Neck Neoplasms

Mouth Diseases

Stomatognathic Diseases

Parotid Diseases

Salivary Gland Diseases

Oral Cancer

All patients will be offered radical adjuvant proton beam therapy to a dose of 60-66 Gray (Gy) in 30-33 fractions delivered Monday to Friday over 6-6.5 weeks.

Proton Beam Therapy

Romelie Rieu

Sally Falk

Chris Nutting

Proton Beam Therapy (PBT) is an advanced radiotherapy technique. There are two National Health Service (NHS) PBT treatment centres in the UK, one in Manchester and one in London. The NHS is committed to ensuring the best use of this limited resource by investigating which patients will benefit from PBT treatment.

Evaluative Commissioning in Protons (ECIP) is a programme of studies that explore the role of PBT for patients with different types of cancer. They are funded by NHS England. ECIP studies are not randomised studies, which means that all eligible patients will be offered proton therapy. Any patient in the United Kingdom (UK) can be referred, and for patients that need to travel far to their nearest centre, accommodation will be available.

The main benefit of PBT, compared with photon radiotherapy, is the predicted reduction in radiation dose to surrounding healthy tissues. With photon radiotherapy, some radiation passes beyond the target area, affecting healthy tissues and causing side-effects. With PBT, the radiation dose stops within the target area, causing less damage to surrounding tissues, and limiting side effects.

PRONTO is a study within the ECIP programme exploring whether PBT can reduce treatment side effects for patients with salivary gland cancers who need radiotherapy following surgery. Whilst radiotherapy is associated with good cancer control, it commonly causes problematic side-effects such as loss of taste and dry mouth. These can be permanent and can negatively affect someone's quality of life. PRONTO's main aim is to see if PBT can reduce the loss of taste following radiotherapy.

Participants in PRONTO will be closely monitored by the medical team and with questionnaires. The patient experience will be compared to what we would expect with standard photon radiotherapy.

Malignant parotid tumours are uncommon. Whilst 85% of salivary gland tumours originate in the parotid gland, only 20-25% of these are malignant, representing only 3-6% of head and neck cancers. This is about 650 patients/year in the UK.

Standard treatment for local disease is with surgical resection followed by adjuvant radiotherapy for patients with high-risk features. Local control and 5-year survival rates are good, at \>70% and \>80% respectively, but radiotherapy is associated with considerable toxicity. More than 70% of patients receiving photon therapy experience significant dysgeusia (taste loss/alteration). This can be permanent, is associated with weight loss, diminished appetite, dry mouth, and negatively impact on Quality of Life (QoL).

The putative benefit of proton beam radiotherapy (PBT) relates to its characteristic deposition in the body, which limits the radiation dose received by surrounding healthy tissues. We hypothesise that irradiating the post-operative parotid bed with PBT rather than Intensity Modulated Radiation Therapy (IMRT), will reduce the dose delivered to the Organs at Risk (OAR), in particular the oral cavity (OC), leading to a reduction in acute and long term taste loss/alteration. The advantageous physical properties of PBT may also improve other side effects including fatigue, mucositis, nausea \& vomiting and potentially hearing problems, as well as overall QoL.

Radiotherapy planning studies:

Radiation planning studies have repeatedly shown statistically significant reductions in the dose delivered to healthy tissues including: the oral cavity, brainstem, spinal cord, contralateral parotid, ipsilateral and contralateral submandibular glands and ipsilateral temporal lobe. In particular, radiotherapy doses to the oral cavity are significantly reduced, typically to below 10 Gray (Gy). No routinely contoured OAR or region of interest was consistently found to have higher doses planning with protons, although skin dose may be higher.

Clinical Trials:

Whilst there are no randomised control trials comparing protons and photons for this cohort. However, there is some clinical evidence that the use of PBT leads to clinically meaningful improvements in the side effects experienced by patients. One study compared acute toxicities between matched groups receiving either protons or photons, demonstrating statistically significant reductions in dysgeusia, fatigue, mucositis and nausea and vomiting in patients undergoing proton treatment. In other studies, PBT is associated with very low toxicity level, such as less than 30% of patients experiencing any dysgeusia. This compares favourably to photon experience, such as in the phase 3 randomised controlled trial 'A Multicentre Randomised Study of Cochlear Sparing Intensity Modulated Radiotherapy Versus Conventional Radiotherapy in Patients with Parotid Tumours' (COSTAR) where approximately 60% of patients reported dysgeusia in the Head \& Neck 35 (HN35) questionnaire at 1 year. The PRONTO study is powered to identify a clinically meaningful reduction in taste dysfunction of at least 20%.

Whilst late toxicities are also likely under-reported in the retrospective international data, the published literature to date is very reassuring. The mean dose to the ipsilateral temporal lobe is reportedly reduced, and reflected in low levels of subsequent headache, fatigue and/or memory change. Similarly, whilst poorly captured, low levels of hearing dysfunction or otalgia have also been reported following PBT.

There is no rationale at all that cancer outcomes, either local control or overall survival, will be worse with PBT than photon treatment. In studies to date, local control (approximately 95%) and overall survival (89%-96%) has been excellent, and comparative to known photon experience.

Evaluative commissioning study. This is a single arm, non-randomised study.

Investigating the Role of Adjuvant Proton Beam Therapy in Patients With Parotid Carcinoma

An Evaluative Commissioning Study to Investigate the Role of Adjuvant Proton Beam Radiotherapy in Patients With Localised Parotid Carcinoma

Taste dysfunction as recorded on the European Organisation for the Research \& Treatment of Cancer (EORTC) Head \& Neck 43 (HN43) patient reported questionnaire.

43 questions with a Likert scale of 1 - 4 Higher score may mean a worse outcome

Using the CTCAE toxicity grade Grades 1 - 5 Higher score may mean a worse outcome

Using the LENT-SOMA scale A multiple item scoring system composed of four domains; subjective, objective, management and analytic.

Grades 0-4 Higher score may mean a worse outcome

Using pure tone audiometry to measure hearing changes Loss of hearing may mean a worse outcome

Using the EORTC QLQ-C30 30 questions using a Likert scale of 1-4 Higher score may mean a worse outcome

Using the EORTC HN43 patient reported questionnaire 43 questions using a Likert scale of 1-4 Higher score may mean a worse outcome

Using the UW-QoL questionnaire Most questions are scored on a Likert scale, 0=worst, 100=best Lower score may mean worse outcomes

Using the GHABP questionnaire Possible values for response options (0=not applicable, 5=cannot manage at all) Higher score may mean worse outcomes

This will be measured as time to recurrence (measured in months from completion of treatment) and location of recurrence (within the primary nodal regional or distant spread)

This will be measured in months from completion of treatment to death

Number of patients referred to and participating in the study annually

Review the number of patients completing radiotherapy and the number of patients completing follow up on the study as per protocol.

Patients will be re-planned with photon radiotherapy, the dose distribution differences between the treatment proton plans and photon plans will be recorded in particular the dose to the oral cavity

Royal Marsden NHS Foundation Trust

University College London Hospitals

The Christie NHS Foundation Trust

Sarcoma

Neoplasms, Connective and Soft Tissue

Soft Tissue Sarcoma

Arm A: Protons, 39 Gy (RBE) in 13 fractions (single dose 3.0 Gy(RBE))

Arm B: Carbon ions, 39 Gy(RBE) in 13 fractions (single dose 3.0 Gy(RBE))

proton irradiation with a total dose of 39 Gy(RBE) in 3 Gy(RBE) fractions

Protons

carbon ion irradiation with a total dose of 39 Gy(RBE) in 3 Gy(RBE) fractions

Klaus Herfarth, Prof. Dr.

Klaus Herfarth

This randomized prospective open-label phase 2 trial testes the safety and feasibility of a hypofractionated accelerated neoadjuvant proton or carbon ion radiotherapy based on the rate of wound healing disorders from beginning of radiotherapy to maximum 120 days after the planned tumor resection or discontinuation of treatment due to any reason. The treatment is of shorter duration (2-3 weeks vs. 5 weeks standard treatment), which should please most patients and thus enhance quality of life. The treatment regimen furthermore promises a reduced rate of late side effects and significant optimization of the current treatment standards. A phase II trial is mandatory not only for obtaining the safety and feasibility data, but also in order to prepare a concurrent phase III trial. Due to the low incidence of soft tissue sarcoma, only a well prepared multicenter study has a chance to be successfully completed based on previous experiences in trials for seldom tumor entities.

Oncologic complete local excision (wide resection) combined with radiotherapy forms the standard treatment for patients with soft tissue sarcoma. Especially patients with G2/G3 sarcomas profit from the combination of radiotherapy and surgery. Well-differentiated sarcomas (G1) after total resection (R0) receive no subsequent treatment besides surgery. The sequence of surgery and radiation therapy is widely discussed by the radiation oncologists and surgeons. The main advantages of neoadjuvant (pre-operative) radiotherapy are the smaller treatment target volumes and reduced prescribed radiation doses of 50 Gy vs. 66 Gy (postoperative) in 2 Gy single doses. Thus, due to these reductions in volumes and dose, neoadjuvant radiotherapy is associated with a lower rate of radiotherapy-associated edema and fibrosis. However, a randomized phase III study showed an increased rate of wound healing complications in patients with neoadjuvant radiotherapy compared to adjuvant (post-operative) radiotherapy (35% vs. 17%). For this reason, adjuvant radiotherapy in is currently preferred in cases with good operability.

Particle therapy bears the chance to utilize the advantages of preoperative radiotherapy without compromising wound healing. The advantages of tumor treatment by ion therapy are based on their special biological and physical features. Protons and carbons ion lead to an improved dose distribution compared to photons which allows an improved sparing of the neighboring risk organs and at the same time an escalation of the dose prescribed to the tumor. Carbon ions are furthermore superior to protons by biological advantages based on their enhanced biological effectivity. In general, heavy ions are considered as a good treatment option for tumors of low radiosensitivity as sarcomas. Superior survival and decreased toxicity rates are expected from the use of protons and carbon ions.

This randomized prospective open-label phase 2 trial testes the safety and feasibility of a hypofractionated accelerated neoadjuvant proton or carbon ion radiotherapy based on the rate of wound healing disorders from beginning of radiotherapy to maximum 120 days after the planned tumor resection or discontinuation of treatment due to any reason. The treatment is of shorter duration (2-3 weeks vs. 5 weeks standard treatment), which should please most patients and thus enhance quality of life. The treatment regimen furthermore promises a reduced rate of late side effects and significant optimization of the current treatment standards. A phase II trial is mandatory not only for obtaining the safety and feasibility data, but also in order to prepare a concurrent phase III trial. Due to the low incidence of soft tissue sarcoma, only a well prepared multicenter study has a chance to be successfully completed based on previous experiences in trials for seldom tumor entities.

Neoadjuvant Irradiation of Extremity Soft Tissue Sarcoma With Ions

Proportion of therapies without wound healing disorders and / or discontinuation in each study arm.

LC: Local control determined from local onset to local tumor progression

LPFS: locally progression-free survival determined from onset of therapy to local tumor progression

DFS: Disease-free survival determined from onset of therapy until local and / or distant tumor progression

OS: Overall survival until death or censorship

University Hospital Heidelberg

Prof. Dr. Dr.

Arm A (carbon ion therapy):

Total dose to the PTV2 - 45 Gy E in 3 Gy E /d, 4-6 days a week, 15 fractions Total dose to the PTV1 - 63 Gy E ± 5%, further 5-7 fractions a 3 Gy E.

Arm B (proton therapy):

Total dose to the PTV2 - 50 to 56 Gy E in 2 Gy E /d, 4-6 days a week, 28 fractions Total dose to the PTV1 - 72 Gy E ± 5%, further 6-9 fractions a 2 Gy E.

Carbon ion

Anna V. Nikoghosyan, MD

Juergen Debus, MD, PhD

Juergen Debus, MD PhD

This study is a prospective randomised clinical phase III trial. The primary objective of this study is to evaluate, if the innovative therapy (carbon ion irradiation) in chordomas is superior to the standard proton treatment with respect to the local-progression free survival (LPFS).

The study is a prospective randomised clinical phase III trial. The trial will be carried out at Heidelberger Ionenstrahl-Therapie (HIT) centre as monocentric trial.

Proton therapy is the gold standard in the treatment of skull base chordomas. However, high-LET beams such as carbon ions theoretically offer biologic advantages by enhanced biologic effectiveness in slow-growing tumors. Up until now it was impossible to compare two different particle therapies, i.e. proton and carbon ion therapy directly with each other. The aim of this study is to find out, whether the biological advantages of carbon ion therapy mentioned above can also be clinically confirmed.

Patients with skull base chordoma will be randomised to either proton or carbon ion radiation therapy. As a standard, patients will undergo non-invasive, rigid immobilization and target volume delineation will be carried out based on CT and MRI data. The biologically isoeffective target dose to the PTV in carbon ion treatment (accelerated dose) will be 63 Gy E ± 5% and 72 Gy E ± 5% (standard dose) in proton therapy respectively. Local-progression free survival (LPFS) will be analysed as primary end point. Toxicity and survival are the secondary end points. Also matters of interest are patterns of recurrence, prognostic factors and plan quality.

Trial of Proton Versus Carbon Ion Radiation Therapy in Patients With Chordoma of the Skull Base

Randomised Trial of Proton vs. Carbon Ion Radiation Therapy in Patients With Chordoma of the Skull Base -Clinical Phase III Study-

The primary objective of this study is to evaluate, if the innovative therapy (carbon ion irradiation) in chordomas is superior to the standard proton treatment with respect to the LPFS defined as time from the randomisation to observed local reccurrence or death from any cause in the absence of documented local disease progression. Lo-cal recurrence defined as MRT or CT - morphological tumor progress in the former irradiated region. A 10% increase in the LPFS is considered clinically relevant as-suming that the LPFS rate for the proton therapy is 70%.

Assessment of overall survival, progression free and metastasis free survival.

Local recurrences will be confirmed radiologically and histologically whenever possible. At least two medical doctors (radiation oncologist and/or radiologist) will be required to judge of the recurrence.

Acute and late toxicity will be analysed due to Common Terminology Criteria for Adverse Events: CTCAE V4.0 for acute reaction and RTOG/EORTC for late effects.

Juergen Debus, MD PhD, Dept. of Radiation Oncology, INF 400, 69120 Heidelberg

Cholangiocarcinoma

Klatskin Tumor

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Bile Duct Cancer

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Gemcitabine

Capecitabine

Cisplatin

Liver Extracts

Antimetabolites

All patients to be offered neoadjuvant proton beam therapy to a dose of 45 Gray (Gy) in 15 fractions over 3 weeks, with a tumour boost to 67.5 Gray (Gy), and alongside concurrent oral capecitabine 625mg/m2 twice daily on radiation days.

All patients to be offered neoadjuvant proton beam therapy to a dose of 45 Gray (Gy) in 15 fractions over 3 weeks, with a tumour boost to 67.5 Gray (Gy)

All patients to be offered concurrent oral capecitabine 625mg/m2 twice daily on radiation days

Concurrent oral capecitabine chemotherapy

Following chemoradiotherapy (PBT + capecitabine), and whilst on the liver transplant waiting list, patients will be offered up to 6 cycles of standard chemotherapy with cisplatin and gemcitabine.

Cisplatin & Gemcitabine intravenous chemotherapy

If still eligible after neoadjuvant treatment (PBT + capecitabine), patients will be added to the liver transplant waiting list.

Orthotropic Liver Transplant

Maria Hawkins

Douglas Thorburn

Proton Beam Therapy (PBT) is an advanced radiotherapy technique. There are two National Health Service (NHS) PBT treatment centres in the United Kingdom (UK), in Manchester and London. The NHS is committed to ensuring the best use of this limited resource by investigating which patients will benefit from PBT.

Evaluative Commissioning in Protons (ECIP) is a programme of studies exploring the role of PBT in different types of cancer. The studies are funded by NHS England. ECIP studies are not randomised studies, which means that all eligible patients will be offered PBT. Any eligible patient in the UK can be referred, and accommodation is available for patients who don't live close to a PBT centre.

The main benefit of PBT, compared with standard photon radiotherapy, is the predicted reduction in radiation dose to surrounding healthy tissues. With photon radiotherapy, some radiation passes beyond the target area, affecting healthy tissues and causing side-effects. With PBT, the radiation dose stops within the target area, causing less damage to surrounding tissues, and limiting side effects.

EMPHATIC is a study within the ECIP programme. In EMPHATIC, the investigators are looking to see whether a combination of treatments, including PBT, chemotherapy and a liver transplant, can be used to treat patients with cholangiocarcinoma (bile duct cancer).

EMPHATIC offers patients whose cancer can't be removed with surgery (unresectable) a potentially curative treatment option. There is evidence that liver transplant is a curative treatment option in patients with cholangiocarcinoma. There is a risk that the cancer may grow or spread whilst waiting for a transplant, potentially making patients ineligible. PBT and chemotherapy is thought to be the best way to control the cancer, until a liver transplant can be performed. EMPHATIC will look at how a combination of PBT and chemotherapy, followed by a liver transplant, can be used to curatively treat patients with unresectable cholangiocarcinomas.

Liver and bile duct resection with lymphadenectomy is the standard of care for patients with hilar cholangiocarcinoma. Unfortunately, resection is only possible in a minority of patients for many reasons including, the extent of cancer or the presence of background primary sclerosing cholangitis (PSC). For patients with a background of PSC, liver transplantation is a potential treatment, and it was recently approved as an indication for a commissioned pilot service evaluation of liver transplantation in the UK.

Until recently, the use of liver transplantation for hilar cholangiocarcinoma was confined to a few centres in the United States. The initial publications from the Mayo Clinic and Nebraska, as well as more recent experience from other centres, support strict selection protocols to identify patients likely to benefit from liver transplantation. In 2000, the initial experience at the Mayo Clinic in which 19 patients enrolled in a pre-transplant neoadjuvant therapy protocol was published. 11 patients underwent subsequent liver transplantation. Of the 8 with long term follow up (median 44 months), only one patient developed cancer recurrence. Similarly, the long-term experience of patients in Nebraska, where 11 patients underwent liver transplantation after neoadjuvant chemoradiotherapy was published in 2002. 5 of the 11 patients were alive and disease free at a median follow up of 7.5 years .

Most recent experience is based on adopting the Mayo protocol. In general, the inclusion criteria define patients with early cancers, with a dominant stricture or tumour less than 3cm. Intra and extrahepatic disease including any site of nodal metastases precluded selection. Controversially, histology or cytology was not considered essential for diagnosis of cholangiocarcinoma by most centres. Elevated Ca 19.9 of \>100, Fluorescence In Situ Hybridization (FISH) polysomy 9p21 or tumour mass in the presence of a dominant stricture were considered sufficient for enrolment. Prior (attempts at) trans-peritoneal biopsy was another exclusion criterion based on concerns of increased risk of tumour dissemination. Neoadjuvant therapy involved external beam radiation therapy (EBRT) with concurrent chemotherapy (chemo sensitisation), followed by brachytherapy whenever possible. Patients were then re-staged and remain on systemic chemotherapy until the time of transplant.

A recent review looked at all studies from 2000 until 2019. 20 studies with 428 patients were eligible for analysis. The pooled 1, 3-, and 5-year overall survival rates following liver transplantation without neoadjuvant therapy (n=156) were 71.2%. In patients who had neoadjuvant therapy prior to transplantation (n=272), the survival improved to 82.8% at 1,3 and 5 years respectively.

The cancer recurrence rate was 51.7% in patients who did not receive neoadjuvant therapy compared to 24.1% for patients who had. Only 4 of the 20 studies reported pre-transplant histological confirmation of adenocarcinoma or malignant/suspicious cells on cytology. 98% of liver explants from studies not using neoadjuvant therapy confirmed malignancy, compared to 50.5% in those who had received neoadjuvant therapy. Patients in whom malignancy was not found are presumed to have had complete pathological response to neoadjuvant therapy (approximately 50% following neoadjuvant therapy). Patients with background PSC had better outcomes compared to patients with de novo cancers.

Study Design \& development of an evaluative commissioning study within ECIP:

It is not possible to design EMPHATIC, a study for patients with unresectable cholangiocarcinoma, as a randomised controlled trial (RCT), because there is no ethically acceptable control arm. In an RCT, patients in a theoretical control arm would be offered either no transplant, or no neoadjuvant therapy prior to the transplant. Based on the published literature summarised above, the adverse anticipated outcomes of patients in such a control arm would not be considered justified.

Neoadjuvant therapy is required to control the tumour prior to transplant. In the Mayo protocol described above, patients received external beam (chemo)radiotherapy followed by brachytherapy, and thereafter received chemotherapy until the time of transplant. Unfortunately, in the UK, brachytherapy services were not seen as a viable option, and hence the Mayo protocol is not feasible.

There is good scientific rationale that proton beam radiotherapy (PBT) offers the optimal technique for delivering neoadjuvant therapy as it is non-invasive, and spares as much functional liver as possible, compared with alternatives such as photon-EBRT techniques or invasive techniques (e.g. brachytherapy). Compared with photon-EBRT techniques, PBT delivers highly conformal radiotherapy, with a significantly reduced integral body dose, and no exit beam. It is expected to be associated with an improved toxicity profile.

Evaluation of Combined Modality Protons and Hepatic Transplantation for Hilar Cholangiocarcinoma

Evaluation of Combined Modality Protons and Hepatic Transplantation for Hilar Cholangiocarcinoma (an Evaluative Commissioning in Protons Study)

Incidence of Grade ≥ 3 toxicity using CTCAE (grades 0-5) up to 90 days following completion of neoadjuvant (chemo)-PBT and liver transplant. Higher score indicates worse outcome.

The proportion of patients who, following neoadjuvant (chemo)-PBT, undergo a successful liver transplant (measured at 90 days post-transplant).

Number of patients completing planned radiotherapy

Rate of Common Toxicity Criteria for recording Adverse Events (CTCAE) Grade 3 and above toxicity (Grades 0-5). Higher score may mean a worse outcome.

Calculated from date of last PBT treatment and defined as time to death or censoring at 1 year.

Calculated from date of liver transplant and defined as time to death or censoring at 1 year.

Calculated from date of transplant and defined as time to death or censoring at 1 year.

Calculated from the date the patient was added to the transplant waiting list and defined as time to death or censoring at 1 year.

Calculated as time to cancer recurrence or death whichever is earliest, from date of transplant, with censoring at 1 year.

Described as local, regional or metastatic disease

Reported as time to loss of cancer control with censoring at time of transplant

Reported as time to loss of cancer control with censoring at date of removal from transplant waiting list

Surgical complication rates according to Clavien Dindo scale, measured from grades 1-5, higher grade may mean worse outcome.

Review of patient pathway deliverability defined as time interval from patient referral to the start of chemo-PBT treatment

Measured in days from last day of PBT to date of transplant

Measured in weeks from transplant listing date to liver transplant date

Review annual referral rates to the study

Number of patients participating in the study

University College, London

Royal Free Hospital NHS Foundation Trust

Ear, Nose, and Throat Diseases

Behaviors and Mental Disorders

Tonsillar Neoplasms

Oropharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Pharyngeal Diseases

Otorhinolaryngologic Diseases

Quality of Life

Acute Graft Versus Host Disease

Radiotherapy with either photons or protons.

Radiotherapy

Maria Gebre-Medhin, MD

Iréne Schönström, RN

Ann-Sofie Fransson, MD

Hedda Haugen, MD

Mattias Olin, MD

Britta Lödén, MD

Anna Flejmer, MD

Michael Gubanski, MD

Björn Zackrisson, MD

Johanna Färlin, MD

Zahra Taheri Kadkhoda, MD

Zizana Lovasova, MD

Zuzana Lovasova, MD

Erik Lundin, MD

In this trial, patients with early squamous cell carcinoma of the tonsil with clinical stage T1-2 (p16-positive or p16-negative) N0-1 (p16-positive)/N0-N2b (p16-negative) according to American Joint Committee on Cancer (AJCC) 8th edition, aimed for unimodal and ipsilateral treatment with radiotherapy with curative intent will be included. The patients will be randomized to in a 1:1 ratio to receive radiotherapy with either photons (conventional radiotherapy) versus radiotherapy with protons.

Photon Therapy Versus Proton Therapy in Early Tonsil Cancer.

Locoregional side effects (mucositis, pain, dysphagia, skin reactions and other functional impairment) are monitored weekly according to a modified morbidity scoring scale based on Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer (RTOG/EORTC). Acute radiation morbidity scoring criteria and other side effects are graded according to (Common Toxicity Criteria for Adverse Events (CTCAE) v4.0

Locoregional side effects (mucositis, pain, dysphagia, skin reactions and other functional impairment) are monitored according to a modified morbidity scoring scale based on Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer (RTOG/EORTC). Late radiation morbidity scoring criteria and other side effects are graded according to Common Toxicity Criteria for Adverse Events (CTCAE) v4.0.

Lund University Hospital

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

CyberKnife SBRT

Rachelle Lanciano, MD

Michael Good, RN

Shilecion Cooper, RN

Stereotactic body radiation therapy (SBRT) has been employed in the treatment of prostate cancer. Multiple single institution experiences suggest high biochemical control rates with acceptable toxicity in low risk prostate cancer but efficacy data in unfavorable type prostate cancer is less convincing. CyberKnife-SBRT (CK-SBRT) can be used to escalate radiation dose delivery to the prostate while sparing normal tissue.

The optimal radiation schedule for the curative treatment of prostate cancer remains unknown. Prostate cancer patients receiving radiation therapy are typically treated 5 days per week for 8-9 weeks. Recent data suggest that large radiation fraction sizes are radio-biologically favorable over lower fraction sizes in prostate cancer radiotherapy. The sensitivity of a tumor or normal tissue to fraction size of radiation can be approximated by the alpha-beta ratio. It has been suggested that the alpha/beta ratio for prostate cancer is actually as low as 1.5 implying that the current radiation therapy paradigm for prostate cancer treatment might be fundamentally flawed, as high fraction sizes would be expected to damage tumor more readily.

Typical prostate SBRT doses do not appear to have similar efficacy in higher risk prostate cancer suggesting even higher doses are required. Many techniques including dose escalated external beam radiation therapy (EBRT), proton therapy (PT) and brachytherapy have been employed to increase dose to the prostate. Data from the ASCEND-RT trial utilizing low dose rate brachytherapy boost showed a dramatic 21% improvement in biochemical control at 9 years favoring brachytherapy boost compared to conventional dose escalated EBRT radiation therapy. However, no corresponding benefit was identified in overall survival, incidence of bone metastases or prostate cancer specific mortality while a 3 fold increase in late urinary toxicity was noted.

SBRT is well tolerated with minimal acute and late side effects. In this protocol, CK-SBRT will be used to target the microscopic and gross disease in the prostate, seminal vesicles. An escalated dose of 40 Gy in 5 fractions will be delivered to the entire target volume while any nodules visible within the prostate gland on endorectal MRI will receive 50 Gy in 5 fractions.

CyberKnife Dose Escalation Prostate Cancer Trial

CyberKnife Dose Escalation for Unfavorable and High-risk Prostate Cancer

Genitourinary or Bowel Toxicity as a result of radiation therapy will be reported using

Time in months from completion of SBRT to biochemical failure

time in months from SBRT completion to local failure

time in months from SBRT completion to distant failure

time in months from the date that the patient is determined to be free of disease to the date of known disease recurrence for any measure of disease.

time in months from completion of SBRT to death due to prostate cancer, other causes with active malignancy, or complications from treatment.

ime in months from SBRT completion until death

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ion Irradiation of Sacrococcygeal Chordoma	NCT01811394	Sacral Chordoma	protons carbon ions	18 Years - 80 Years	Heidelberg University
Investigating the Role of Adjuvant Proton Beam Therapy in Patients With Parotid Carcinoma	NCT06421649	Parotid Cancer	Proton Beam The...	18 Years -	The Christie NHS Foundation Trust
Investigating the Role of Adjuvant Proton Beam Therapy in Patients With Parotid Carcinoma	NCT06421649	Parotid Cancer	Proton Beam The...	18 Years -	The Christie NHS Foundation Trust
Ion Irradiation of Sacrococcygeal Chordoma	NCT01811394	Sacral Chordoma	protons carbon ions	18 Years - 80 Years	Heidelberg University
Neoadjuvant Irradiation of Extremity Soft Tissue Sarcoma With Ions	NCT04946357	Soft Tissue Sar...	Protons carbon ions	18 Years -	University Hospital Heidelberg
Trial of Proton Versus Carbon Ion Radiation Therapy in Patients With Chordoma of the Skull Base	NCT01182779	Chordoma Tumor Treatment	Carbon ion Protons	18 Years - 80 Years	Heidelberg University
Evaluation of Combined Modality Protons and Hepatic Transplantation for Hilar Cholangiocarcinoma	NCT06434493	Cholangiocarcin...	Proton Beam The... Concurrent oral... Cisplatin & Gem... Orthotropic Liv...	17 Years -	The Christie NHS Foundation Trust
Photon Therapy Versus Proton Therapy in Early Tonsil Cancer.	NCT03829033	Tonsil Cancer	Radiotherapy	18 Years -	Lund University Hospital
Neoadjuvant Irradiation of Extremity Soft Tissue Sarcoma With Ions	NCT04946357	Soft Tissue Sar...	Protons carbon ions	18 Years -	University Hospital Heidelberg
CyberKnife Dose Escalation Prostate Cancer Trial	NCT03822494	Prostate Cancer Prostate Adenoc... Prostate Neopla...	CyberKnife SBRT	18 Years -	Crozer-Keystone Health System

Spots Global Cancer Trial Database for protons

Every month we try and update this database with for protons cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for protons

Every month we try and update this database with for protons cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for protons cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.