De-escalating radiotherapy in HPV-positive oropharyngeal squamous cell carcinoma: how much is too little?

Oropharyngeal squamous cell carcinoma (OPSCC) had a rapidly increasing incidence rate in high-income countries, with a significant increase in cases related to human papilloma virus (HPV). HPV-positive (HPV+) OPSCC has shown better survival rates compared with HPV-negative (HPV-) cases, prompting investigations into de-escalation strategies to reduce or change chemoradiotherapy protocols. We present a case of a patient with HPV+ OPSCC who discontinued chemoradiotherapy after 2 weeks, effectively receiving a de-escalated dose of 18 Gy over nine fractions and only one cycle of cisplatin, subsequently undergoing curative surgical resection with no residual disease in the radiotherapy field 14 years later. This case challenges the concept of standard radiotherapy dosing in HPV+ OPSCC and discusses the implications on future de-escalation trials.

TORPEdO: A phase III trial of intensity-modulated proton beam therapy versus intensity-modulated radiotherapy for multi-toxicity reduction in oropharyngeal cancer.

•There is a lack of prospective level I evidence for the use of PBT for most adult cancers including oropharyngeal squamous cell carcinoma (OPSCC).•TORPEdO is the UK's first PBT clinical trial and aims to determine the benefits of PBT for OPSCC.•Training and support has been provided before and during the trial to reduce variations of contouring and radiotherapy planning.•There is a strong translational component within TORPEdO. Imaging and physics data along with blood, tissue collection will inform future studies in refining patient selection for IMPT.

Photobiomodulation in the management of oral mucositis for adult head and neck cancer patients receiving irradiation: the LiTEFORM RCT.

BACKGROUND: Oral mucositis is a debilitating and painful complication of head and neck cancer irradiation that is characterised by inflammation of the mucous membranes, erythema and ulceration. Oral mucositis affects 6000 head and neck cancer patients per year in England and Wales. Current treatments have not proven to be effective. International studies suggest that low-level laser therapy may be an effective treatment. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of low-level laser therapy in the management of oral mucositis in head and neck cancer irradiation. To identify barriers to and facilitators of implementing low-level laser therapy in routine care. DESIGN: Placebo-controlled, individually randomised, multicentre Phase III superiority trial, with an internal pilot and health economic and qualitative process evaluations. The participants, outcome assessors and therapists were blinded. SETTING: Nine NHS head and neck cancer sites in England and Wales. PARTICIPANTS: A total of 87 out of 380 participants were recruited who were aged ≥ 18 years and were undergoing head and neck cancer irradiation with ≥ 60 Gy. INTERVENTION: Random allocation (1 : 1 ratio) to either low-level laser therapy or sham low-level laser therapy three times per week for the duration of irradiation. The diode laser had the following specifications: wavelength 660 nm, power output 75 mW, beam area 1.5 cm2, irradiance 50 mW/cm2, exposure time 60 seconds and fluence 3 J/cm2. There were 20-30 spots per session. Sham low-level laser therapy was delivered in an identical manner. MAIN OUTCOME MEASURE: The mean Oral Mucositis Weekly Questionnaire-Head and Neck Cancer score at 6 weeks following the start of irradiation. Higher scores indicate a worse outcome. RESULTS: A total of 231 patients were screened and, of these, 87 were randomised (low-level laser therapy arm, n = 44; sham arm, n = 43). The mean age was 59.4 years (standard deviation 8.8 years) and 69 participants (79%) were male. The mean Oral Mucositis Weekly Questionnaire-Head and Neck Cancer score at 6 weeks was 33.2 (standard deviation 10) in the low-level laser therapy arm and 27.4 (standard deviation 13.8) in the sham arm. LIMITATIONS: The trial lacked statistical power because it did not meet the recruitment target. Staff and patients willingly participated in the trial and worked hard to make the LiTEFORM trial succeed. However, the task of introducing, embedding and sustaining new low-level laser therapy services into a complex care pathway proved challenging. Sites could deliver low-level laser therapy to only a small number of patients at a time. The administration of low-level laser therapy was viewed as straightforward, but also time-consuming and sometimes uncomfortable for both patients and staff, particularly those staff who were not used to working in a patient's mouth. CONCLUSIONS: This trial had a robust design but lacked power to be definitive. Low-level laser therapy is relatively inexpensive. In contrast with previous trials, some patients found low-level laser therapy sessions to be difficult. The duration of low-level laser therapy sessions is, therefore, an important consideration. Clinicians experienced in oral cavity work most readily adapt to delivering low-level laser therapy, although other allied health professionals can be trained. Blinding the clinicians delivering low-level laser therapy is feasible. There are important human resource, real estate and logistical considerations for those setting up low-level laser therapy services. FUTURE WORK: Further well-designed randomised controlled trials investigating low-level laser therapy in head and neck cancer irradiation are needed, with similar powered recruitment targets but addressing the recruitment challenges and logistical findings from this research. TRIAL REGISTRATION: This trial is registered as ISRCTN14224600. FUNDING: This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 46. See the NIHR Journals Library website for further project information.

Around 9 out of 10 head and neck cancer patients undergoing treatment experience pain, swelling and sores in their mouth (oral mucositis). This can lead to weight loss, painful ulcers, difficulty talking, eating and drinking, and even hospitalisation. Current care includes helping patients to keep their mouth and teeth clean, encouraging them to have a healthy diet and prescribing mouthwashes, painkillers and mouth-coating gels. However, these treatments give limited help in preventing or treating this condition. The LiTEFORM trial looked at whether or not low-level laser therapy could be used to prevent and treat oral mucositis. Patients were allocated to one of two arms at random: active laser or fake (sham) laser. Neither the patients nor the hospital staff knew which laser was being used. Eighty-seven people joined the study during the time allowed (44 received low-level laser therapy and 43 received sham treatment); however, this was a smaller number than the planned target of 380 people. As a result, no meaningful conclusion can be drawn from the results about whether the therapy is beneficial or cost-effective. People receiving the low-level laser therapy reported slightly more soreness in their mouth than those receiving the sham laser, but this could be down to chance. The number of participants is too small to draw conclusions about whether or not the low-level laser is helpful. Some patients found the laser treatment sessions to be difficult. Setting up a new service delivering laser therapy at the same time as cancer treatments was more complicated than originally anticipated. Problems included the scheduling of appointments, finding suitable rooms and having enough trained staff with time to deliver laser therapy. However, this study has provided us with knowledge on how best to set up a laser therapy service in the NHS as part of the cancer treatment pathway and the costs involved. These findings could help future studies looking into low-level laser therapy for those with head and neck cancer.

Effects of cardiopulmonary bypass perfusion temperature on perioperative renal function in adult patients undergoing cardiac surgery.

AIMS AND OBJECTIVE: The primary objective of this investigation was to study the effects of cardiopulmonary bypass (CPB) perfusion temperature on renal function parameters [serum creatinine, creatinine clearance, urine albumin, urine protein, and urine albumin/creatinine ratio (ACR)]. The secondary objective was to detect renal complications of CPB. MATERIALS AND METHODS: This is a prospective longitudinal study of 30 adult patients (17 men, 13 women; mean age, 53.37 ± 16.02 years) who underwent valvular heart surgery [with or without coronary artery bypass grafting (CABG)]. Serum creatinine, creatinine clearance, urine protein, urine albumin, and urine ACR were collected during CPB (at 28 °C, 32 °C, and 37 °C) and postoperatively (at 12 hours, 24 hours, and 48 hours). Data were analyzed using one-way repeated-measures analysis of variance (ANOVA). A significant ANOVA was followed by a Bonferroni-Holm post hoc test. RESULTS: Although serum creatinine (p < 0.001) and creatinine clearance (p = 0.0016) underwent a significant ANOVA change (p < 0.001 and p = 0.0016, respectively) after CPB, there was no statistically significant change compared with their baseline values. Urine ACR showed a significant change at 28 °C (p < 0.01), 32 °C (p < 0.01), and 37 °C (p < 0.05) as compared with baseline values. No significant change in urine albumin was observed during CPB or up to 24 hours. A significant change occurred after 48 hours of CPB (p < 0.05). A significant increase in urine protein was noted after CPB at 12 hours (p < 0.01), 24 hours (p < 0.01), and 48 hours (p < 0.01). Overall, 12 (40%) patients had acute kidney injury (AKI). Ten (33.33%) patients had stage I AKI, one patient progressed to AKI stage II, and another to AKI stage III. Of the 10 patients who had stage I AKI, eight had complete recovery within 48 hours. CONCLUSIONS: CPB with moderate hypothermia for valvular heart surgeries can be performed safely in patients with adequate renal functional reserve. The glomerular permeability across the Bowman's capsule increases after CPB as evidenced by significant proteinuria at 12 hours and increased albuminuria at 48 hours after surgery. There is an increased risk of transient stage I AKI after CPB, from which patients recover within 48 hours.