HTA of carbon ion beam radiotherapy for cancer treatment in Austria

Carbon ion radiotherapy (CIRT) is a type of radiation therapy and belongs, together with other charged particles such as protons, helium or neon, to the group of hadron therapy. CIRT is claimed to be both more effective and safer than traditional radiotherapy due to its physical dose distribution and its higher relative biological effectiveness (RBE). Moreover, CIRT is expected to have a higher local control of a tumour than the traditional radiotherapy while minimizing the probability of damaging the surrounding healthy tissues. However, CIRT may also have its negative aspects for specific indications, since a) the treated volume extends the gross tumour volume and thus, healthy tissues may be affected by high LET (linear energy transfer) and b) tumours may be intertwined with, or embedded in, healthy tissues.

The authors have conducted search in four (4) databases (Cochrane CENTRAL, CRD, Embase and Ovid MEDLINE) in order to identify studies that focus on the efficacy or safety of CIRT. They considered the publications in English, German and French, only. In addition, a desk search was conducted on the websites of the cancer therapy centres currently offering CIRT, and the particle therapy co-operative group (PTCOG) to identify further relevant published and ongoing studies respectively.

Fifty-six (56) studies elaborating on the efficacy and/or safety of CIRT have been identified. These studies demonstrate that the most frequent indications were skull-based tumours (brain included), prostate, lung region and ENT region. Out of these, twenty-seven (27) clinical studies were eligible and thus considered for the review, one (1) of those being an RCT, while others were mostly prospective case series (20), case-control studies (3) and single-arm before-after studies (3), which focused on HRQoL. Having reviewed these studies, the authors found no scientific evidence for 41 indications and insufficient scientific evidence for 13 indications:

• Skull base: weak scientific evidence indicating superiority/inferiority of CIRT for chordomas and low-grade chondrosarcoma when compared to conventional radiotherapy (evidence base: three (3) uncontrolled prospective case series studies). No scientific evidence was found for eleven (11) other skull base tumours
• Eye: no scientific evidence indicating superiority/inferiority regarding efficacy or safety of CIRT when compared to conventional radiotherapy
• Brain: insufficient scientific evidence that would indicate superiority/inferiority of CIRT for WHO grade II and WHO grade III-IV brain tumours when compared to conventional radiotherapy (evidence base: two (2) studies). No scientific evidence regarding inferiority/superiority of CIRT was found for ependymoma, medulloblastoma, and “other childhood brain tumours”
• Ear-Nose-Throat (ENT): insufficient scientific evidence indicating superiority/inferiority of CIRT regarding efficacy or safety for sarcomas in the head and neck, tumours in the nasal cavity and paranasal sinus and adenoid cystic salivary gland carcinomas (evidence base: one (1) case-control study and four (4)prospective case series). No scientific evidence regarding superiority/inferiority of CIRT when compared to standard irradiation was found for eight (8) other specific indications in the ENT region: orbital tumours, maxillary sinus carcinoma, nasopharyngeal carcinoma, oropharyngeal carcinoma, tonsil carcinoma, tongue base carcinoma, pleomorphic salivary gland carcinoma, rhabdomyosarcoma
• Lung: insufficient scientific evidence indicating superiority/inferiority of CIRT for non-small cell lung cancer (NSCLC) when compared to conventional radiotherapy (evidence base: two (2) case-control studies and 4 prospective case series)
• Gastrointestinal tumours: insufficient scientific evidence indicating superiority/inferiority of CIRT regarding efficacy or safety for thoracic oesophageal squamous cell carcinoma and rectal cancer without distant metastases when compared to conventional radiotherapy (evidence base: one (1) prospective case series respectively). No scientific evidence indicating superiority/inferiority of CIRT regarding efficacy or safety when compared to standard irradiation was found for pancreatic cancer, liver carcinoma, (malignant) schwannomas, and Ewing’s sarcomas
• Bone and soft tissue sarcoma: insufficient scientific evidence indicating superiority/inferiority of CIRT regarding efficacy or safety was found for soft tissue sarcoma (localized primary sarcoma of the extremities) when compared to conventional radiotherapy (evidence base: one (1) prospective case series study). No scientific evidence indicating superiority/inferiority of CIRT regarding efficacy or safety when compared to standard irradiation was found for osteosarcoma, sacral chordoma, sacral chondrosarcoma and spinal meningioma
• Prostate: insufficient scientific evidence indicating superiority/inferiority of CIRT regarding efficacy or safety (evidence base: one (1) RCT focusing on feasibility and toxicity, three (3) before-after studies focusing on HRQoL and four (4) prospective case series)
• Breast: no scientific evidence indicating superiority/inferiority regarding efficacy or safety of CIRT when compared to conventional radiotherapy
• Kidney: no scientific evidence indicating superiority/inferiority regarding efficacy or safety of CIRT when compared to conventional radiotherapy for nephroblastoma
• Central nervous system: no scientific evidence indicating superiority/inferiority regarding efficacy or safety of CIRT when compared to conventional radiotherapy for neuroblastoma
• Hematologic cancer: no scientific evidence indicating superiority/inferiority regarding efficacy or safety of CIRT when compared to conventional radiotherapy for Non-Hodgkin’s lymphoma and Hodgkin’s lymphoma
• Other oncologic indications: no scientific evidence indicating superiority/inferiority regarding efficacy or safety of CIRT when compared to conventional radiotherapy for solitary liver metastases in colorectal cancer, retroperitoneal metastases in controlled primary tumours, and oligo-metastasis in controlled primary tumours in selected indications

The authors note that there are sixty-five (65) ongoing studies in this field, but only ten (10) of those are controlled trials, while there are four (4) finished RCTs which have not been published yet.

The authors conclude that CIRT must be considered an experimental procedure, due to the lack of scientific evidence.

See the full report in English (with summary in German) here.

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