scholarly journals Reduced radiation-induced toxicity by using proton therapy for the treatment of oropharyngeal cancer

2020 ◽  
Vol 93 (1107) ◽  
pp. 20190955 ◽  
Author(s):  
Tineke W.H. Meijer ◽  
Dan Scandurra ◽  
Johannes A. Langendijk
Keyword(s):  
Squamous Cell Carcinoma ◽  
Side Effects ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Proton Therapy ◽  
Oropharyngeal Cancer ◽  
Organs At Risk ◽  
Tube Feeding ◽  
Well Being ◽  
Radiation Induced

Patients with squamous cell carcinoma of the oropharynx are generally treated with (chemo) radiation. Patients with oropharyngeal cancer have better survival than patients with squamous cell carcinoma of other head and neck subsites, especially when related to human papillomavirus. However, radiotherapy results in a substantial percentage of survivors suffering from significant treatment-related side-effects. Late radiation-induced side-effects are mostly irreversible and may even be progressive, and particularly xerostomia and dysphagia affect health-related quality of life. As the risk of radiation-induced side-effects highly depends on dose to healthy normal tissues, prevention of radiation-induced xerostomia and dysphagia and subsequent improvement of health-relatedquality of life can be obtained by applying proton therapy, which offers the opportunity to reduce the dose to both the salivary glands and anatomic structures involved in swallowing. This review describes the results of the first cohort studies demonstrating that proton therapy results in lower dose levels in multiple organs at risk, which translates into reduced acute toxicity (i.e. up to 3 months after radiotherapy), while preserving tumour control. Next to reducing mucositis, tube feeding, xerostomia and distortion of the sense of taste, protons can improve general well-being by decreasing fatigue and nausea. Proton therapy results in decreased rates of tube feeding dependency and severe weight loss up to 1 year after radiotherapy, and may decrease the risk of radionecrosis of the mandible. Also, the model-based approach for selecting patients for proton therapy in the Netherlands is described in this review and future perspectives are discussed.

scholarly journals Proton Therapy for HPV-Associated Oropharyngeal Cancers of the Head and Neck: a De-Intensification Strategy

2021 ◽  
Vol 22 (6) ◽  
Author(s):  
Nicolette Taku ◽  
Li Wang ◽  
Adam S. Garden ◽  
David I. Rosenthal ◽  
G. Brandon Gunn ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Proton Therapy ◽  
Oropharyngeal Cancer ◽  
Phase Iii ◽  
Proton Radiation ◽  
Regional Lymph Nodes ◽  
Intensity Modulated

Opinion statementThe rise in the incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPC), the relatively young age at which it is diagnosed, and its favorable prognosis necessitate the use of treatment techniques that reduce the likelihood of side effects during and after curative treatment. Intensity-modulated proton therapy (IMPT) is a form of radiotherapy that de-intensifies treatment through dose de-escalation to normal tissues without compromising dose to the primary tumor and involved, regional lymph nodes. Preclinical studies have demonstrated that HPV-positive squamous cell carcinoma is more sensitive to proton radiation than is HPV-negative squamous cell carcinoma. Retrospective studies comparing intensity-modulated photon (X-ray) radiotherapy to IMPT for OPC suggest comparable rates of disease control and lower rates of pain, xerostomia, dysphagia, dysgeusia, gastrostomy tube dependence, and osteoradionecrosis with IMPT—all of which meaningfully affect the quality of life of patients treated for HPV-associated OPC. Two phase III trials currently underway—the “Randomized Trial of IMPT versus IMRT for the Treatment of Oropharyngeal Cancer of the Head and Neck” and the “TOxicity Reduction using Proton bEam therapy for Oropharyngeal cancer (TORPEdO)” trial—are expected to provide prospective, level I evidence regarding the effectiveness of IMPT for such patients.

Randomized trial of radiotherapy with weekly cisplatin or cetuximab in low risk HPV associated oropharyngeal cancer (TROG 12.01): A Trans-Tasman Radiation Oncology Group study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6012-6012
Author(s):  
Danny Rischin ◽  
Madeleine T. King ◽  
Lizbeth M. Kenny ◽  
Sandro Porceddu ◽  
Christopher Wratten ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Symptom Severity ◽  
Oropharyngeal Cancer ◽  
Symptom Burden ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Low Risk ◽  
Free Survival ◽  
Weekly Cisplatin

6012 Background: The excellent prognosis of patients with low risk HPV associated oropharyngeal squamous cell carcinoma has led to concerns about overtreatment and excessive toxicity with radiotherapy and cisplatin, leading to interest in de-intensification trials. We investigated whether cetuximab, an EGFR targeting antibody, when combined with radiotherapy would result in a decrease in symptom burden and toxicity with similar efficacy when compared to weekly cisplatin. Methods: TROG 12.01, a randomised, multicentre trial involving 15 sites in Australia and New Zealand enrolled patients with HPV associated oropharyngeal squamous cell carcinoma, AJCC 7th edition Stage III (excluding T1-2N1) or stage IV (excluding T4 and/or N3 and/or N2b-c if smoking history >10 pack years and/or distant metastases). Patients were randomised (1:1) to receive radiotherapy (70Gy in 35 fractions) with either weekly cisplatin, 7 doses of 40mg/m2 or cetuximab, loading dose of 400mg/m2 followed by 7 weekly doses of 250 mg/m2. The primary outcome was symptom severity assessed by the MD Anderson Symptom Inventory Head and Neck Symptom Severity Scale from baseline to 13 weeks post completion of radiotherapy using the area under the time-severity curve (AUC). Sample size was 170 evaluable patients to provide at least 90% power to detect an effect size of 0.5, using a 2-sided test at 0.05 level of significance. Trial was registered on ClinicalTrials.gov: NCT01855451. Results: Between 17th June 2013 and 7th June 2018, 189 patients were enrolled and 182 were evaluable, with 92 on cisplatin arm and 90 on cetuximab included in the main analysis. The median follow-up was 4.1 years (0.4 - 5.3). Analyses were performed in all eligible randomised patients that commenced treatment (modified intention-to-treat population). There was no difference in the primary endpoint of symptom severity; difference in AUC cetuximab – cisplatin was 0.05 (95%CI: -0.19, 0.30), p= 0.66. The T-score (mean number of > grade 3 acute adverse events) was 4.35 (SD 2.48) in the cisplatin arm and 3.82 (SD 1.8) in the cetuximab arm, p= 0.108. The 3 -year failure-free survival rates were 93% (95% CI: 86-97%) in the cisplatin arm and 80% (95% CI: 70-87%) in the cetuximab arm (hazard ratio = 3.0 (95% CI: 1.2-7.7); p=0.015. The increase in failures in the cetuximab arm was evenly split between distant and locoregional failures. Conclusions: For patients with low risk HPV associated oropharyngeal cancer, radiotherapy and cetuximab had inferior failure-free survival without improvement in symptom burden or toxicity compared to radiotherapy and weekly cisplatin. Radiotherapy and cisplatin remains the standard of care. Clinical trial information: NCT01855451.

scholarly journals Proton therapy for non-squamous cell carcinoma of the head and neck: planning comparison and toxicity

2019 ◽  
Vol 60 (5) ◽  
pp. 612-621 ◽  
Author(s):  
Hiromitsu Iwata ◽  
Toshiyuki Toshito ◽  
Kensuke Hayashi ◽  
Maho Yamada ◽  
Chihiro Omachi ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Proton Therapy ◽  
Patient Specific ◽  
Dose Distributions

Abstract To investigate optimal treatment planning using proton beams for non-squamous cell carcinoma of the head and neck (NSCHN), the dose distributions of plans involving pencil beam scanning (PBS) with or without a patient-specific aperture system (PSAS), passive-scattering proton therapy (PSPT) and X-ray intensity-modulated radiotherapy (IMRT) were compared. As clinical results, toxicities of PBS with PSAS, including changes in quality of life, were reported. Between April 2014 and August 2016, a total of 30 patients were treated using PBS with PSAS. In 20 patients selected at random, the dose distributions of PBS with or without the PSAS, PSPT and IMRT plans were compared. Neutron exposure by proton therapy was calculated using a Monte Carlo simulation. Toxicities were scored according to CTCAE ver. 4.0. Patients completed EORTC quality of life survey forms (QLQ-C30 and QLQ-HN35) before and 0–12 months after proton therapy. The 95% conformity number of PBS with the PSAS plan was the best, and significant differences were detected among the four plans (P < 0.05, Bonferroni tests). Neutron generation by PSAS was ~1.1-fold higher, but was within an acceptable level. No grade 3 or higher acute dermatitis was observed. Pain, appetite loss and increased weight loss were more likely at the end of treatment, but recovered by the 3 month follow-up and returned to the pretreatment level at the 12 month follow-up. PBS with PSAS reduced the penumbra and improved dose conformity in the planning target volume. PBS with PSAS was tolerated well for NSCHN.

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