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A systematic review and practical considerations of stereotactic body radiotherapy in the treatment of head and neck cancer.

ABSTRACT:

Objectives

Stereotactic radiotherapy (SBRT) is gaining popularity although its use in head and neck cancer (HNC) is not well defined. The primary objective was to review the published evidence regarding the use of stereotactic radiotherapy in HNC.

Methods

A literature search was performed by using MEDLINE and EMBASE databases for eligible studies from 2000 to 2019 and 26 relevant studies were identified.

Results

Literature demonstrates a heterogeneous use of this technique with regards to patient population, primary or salvage treatment, dose fractionation regimens, outcomes and follow-up protocols. Carotid blow out syndrome is a risk as with other forms of reirradiation but alternative treatment regimens may reduce this risk.

Conclusion

At present there is a lack of evidence regarding SBRT as a primary treatment option for HNC and definitive answers regarding efficacy and tolerability cannot be provided but there is growing evidence that SBRT reirradiation regimens are safe and effective. In lieu of evidence from large Phase III trials, we define appropriate organ at risk constraints and prescription doses, with accurate plan summation approaches. Prospective randomised trials are warranted to validate improved treatment outcomes and acceptable treatment morbidity.

Advances in knowledge

This article provides a comprehensive review of evidence of use of stereotactic radiotherapy in HNC site (either as a primary treatment or as reirradiation). We also provide an evidence-based approach to the implementation and practical consideration of stereotactic radiotherapy in HNC.

SUBMITTER: Iqbal MS

PROVIDER: S-EPMC7774675 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionStereotactic body radiotherapy (SBRT) is increasingly used to treat disease in the oligometastatic (OM) setting due to mounting evidence demonstrating its efficacy and safety. Given the low population representation in prospective studies, we performed a systematic review and meta-analysis of outcomes of HNC patients with extracranial OM disease treated with SBRT.MethodsA systematic review was conducted with Cochrane, Medline, and Embase databases queried from inception to August 2022 for studies with extracranial OM HNC treated with stereotactic radiotherapy. Polymetastatic patients (>five lesions), mixed-primary cohorts failing to report HNC separately, lack of treatment to all lesions, nonquantitative endpoints, and other definitive treatments (surgery, conventional radiotherapy, and radioablation) were excluded. The meta-analysis examined the pooled effects of 12- and 24-month local control (LC) per lesion, progression-free survival (PFS), and overall survival (OS). Weighted random-effects were assessed using the DerSimonian and Laird method, with heterogeneity evaluated using the I2 statistic and Cochran Qtest. Forest plots were generated for each endpoint.ResultsFifteen studies met the inclusion criteria (639 patients, 831 lesions), with twelve eligible for quantitative synthesis with common endpoints and sufficient reporting. Fourteen studies were retrospective, with a single prospective trial. Studies were small, with a median of 32 patients (range: 6-81) and 63 lesions (range: 6-126). The OM definition varied, with a maximum of two to five metastases, mixed synchronous and metachronous lesions, and a few studies including oligoprogressive lesions. The most common site of metastasis was the lung. Radiation was delivered in 1-10 fractions (20-70 Gy). The one-year LC (LC1), reported in 12 studies, was 86.9% (95% confidence interval [CI]: 79.3-91.9%). LC2 was 77.9% (95% CI: 66.4-86.3%), with heterogeneity across studies. PFS was reported in five studies, with a PFS1 of 43.0% (95% CI: 35.0-51.4%) and PFS2 of 23.9% (95% CI: 17.8-31.2%), with homogeneity across studies. OS was analyzed in nine studies, demonstrating an OS1 of 80.1% (95% CI: 74.2-85.0%) and OS2 of 60.7% (95% CI: 51.3-69.4%). Treatment was well tolerated with no reported grade 4 or 5 toxicities. Grade 3 toxicity rates were uniformly below 5% when reported.ConclusionsSBRT offers excellent LC and promising OS, with acceptable toxicities in OM HNC. Durable PFS remains rare, highlighting the need for effective local or systemic therapies in this population. Further investigations on concurrent and adjuvant therapies are warranted.

Project description:BACKGROUND:The efficacy of immunotherapy targeting the PD-1/PD-L1 pathway has previously been demonstrated in metastatic head and neck squamous cell carcinoma (HNSCC). Stereotactic Body Radiotherapy (SBRT) aims at ablating metastatic lesions and may play a synergistic role with immunotherapy. The purpose of this study is to assess the safety and efficacy of triple treatment combination (TTC) consisting of the administration of durvalumab and tremelimumab in combination with SBRT in metastatic HNSCC. METHOD:This is a phase I/II single arm study that will include 35 patients with 2-10 extracranial metastatic lesions. Patients will receive durvalumab (1500?mg IV every 4?weeks (Q4W)) and tremelimumab (75?mg IV Q4W for a total of 4 doses) until progression, unacceptable toxicity or patient withdrawal. SBRT to 2-5 metastases will be administered between cycles 2 and 3 of immunotherapy. The safety of the treatment combination will be evaluated through assessment of TTC-related toxicities, defined as grade 3-5 toxicities based on Common Terminology Criteria for Adverse Events (v 4.03), occurring within 6?weeks from SBRT start, and that are definitely, probably or possibly related to the combination of all treatments. We hypothesize that dual targeting of PD-L1 and CTLA-4 pathways combined with SBRT will lead to <?35% grade 3-5 acute toxicities related to TTC. Progression free survival (PFS) will be the primary endpoint of the phase II portion of this study and will be assessed with radiological exams every 8?weeks using the RECIST version 1.1 criteria. DISCUSSION:The combination of synergistic dual checkpoints inhibition along with ablative radiation may significantly potentiate the local and systemic disease control. This study constitutes the first clinical trial combining effects of SBRT with dual checkpoint blockade with durvalumab and tremelimumab in the treatment of metastatic HNSCC. If positive, this study would lead to a phase III trial testing this treatment combination against standard of care in metastatic HNSCC. TRIAL REGISTRATION:NCT03283605 . Registration date: September 14, 2017; version 1.

Project description:Stereotactic body radiotherapy (SBRT) is a novel noninvasive treatment for hepatocellular carcinoma. SBRT can achieve effective local control, but it requires a relatively high input of resources; this systematic review was performed to assess the cost effectiveness of SBRT in the treatment of hepatocellular carcinoma to provide a basis for government pricing and medical insurance decision-making. The PubMed, EMBASE, Cochrane Library, CNKI, Wanfang and SinoMed databases were searched to collect economic evaluations of SBRT for the treatment of hepatocellular carcinoma from the date of database inception through December 31, 2018. Two reviewers independently screened the studies, extracted the data and performed a descriptive analysis of the basic characteristics, methods of economic evaluation and main results, as well as the quality and heterogeneity of the reports. A total of 5 studies were included. Among them, the level of heterogeneity was relatively acceptable, with a median score of 90%. Four studies were cost-utility analyses (CUAs), and 1 was a cost-effectiveness analysis (CEA). The incremental cost effectiveness ratio (ICER) for sorafenib compared to SBRT was US $114,795 per quality-adjusted life year gained (cost/QALY) in patients with advanced hepatocellular carcinoma. The ICER for proton beam therapy compared to SBRT was US $6465 in patients with inoperable advanced hepatocellular carcinoma. The ICER for SBRT compared to RFA was US $164,660 for patients with unresectable colorectal cancer (CRC) with liver metastases and US $56,301 for patients with early-stage hepatocellular carcinoma. For patients with inoperable localized hepatocellular carcinoma, compared with RFA-SBRT therapy, the ICERs for SBRT-SBRT and SBRT-RFA were US $558,679 and US $2197,000, respectively; RFA-RFA was dominated. In conclusion, there is limited evidence suggesting that SBRT could be cost-effective for highly specific subpopulations of HCC patients, and further economic evaluations based on randomized controlled trials (RCTs) or cohort studies are needed.