Summary Background Xerostomia is the most common late side-effect of radiotherapy to the head and neck. Compared with conventional radiotherapy, intensity-modulated radiotherapy (IMRT) can reduce irradiation of the parotid glands. We assessed the hypothesis that parotid-sparing IMRT reduces the incidence of severe xerostomia. Methods We undertook a randomised controlled trial between Jan 21, 2003, and Dec 7, 2007, that compared conventional radiotherapy (control) with parotid-sparing IMRT. We randomly assigned patients with histologically confirmed pharyngeal squamous-cell carcinoma (T1–4, N0–3, M0) at six UK radiotherapy centres between the two radiotherapy techniques (1:1 ratio). A dose of 60 or 65 Gy was prescribed in 30 daily fractions given Monday to Friday. Treatment was not masked. Randomisation was by computer-generated permuted blocks and was stratified by centre and tumour site. Our primary endpoint was the proportion of patients with grade 2 or worse xerostomia at 12 months, as assessed by the Late Effects of Normal Tissue (LENT SOMA) scale. Analyses were done on an intention-to-treat basis, with all patients who had assessments included. Long-term follow-up of patients is ongoing. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN48243537. Findings 47 patients were assigned to each treatment arm. Median follow-up was 44·0 months (IQR 30·0–59·7). Six patients from each group died before 12 months and seven patients from the conventional radiotherapy and two from the IMRT group were not assessed at 12 months. At 12 months xerostomia side-effects were reported in 73 of 82 alive patients; grade 2 or worse xerostomia at 12 months was significantly lower in the IMRT group than in the conventional radiotherapy group (25 [74%; 95% CI 56–87] of 34 patients given conventional radiotherapy vs 15 [38%; 23–55] of 39 given IMRT, p=0·0027). The only recorded acute adverse event of grade 2 or worse that differed significantly between the treatment groups was fatigue, which was more prevalent in the IMRT group (18 [41%; 99% CI 23–61] of 44 patients given conventional radiotherapy vs 35 [74%; 55–89] of 47 given IMRT, p=0·0015). At 24 months, grade 2 or worse xerostomia was significantly less common with IMRT than with conventional radiotherapy (20 [83%; 95% CI 63–95] of 24 patients given conventional radiotherapy vs nine [29%; 14–48] of 31 given IMRT; p Interpretation Sparing the parotid glands with IMRT significantly reduces the incidence of xerostomia and leads to recovery of saliva secretion and improvements in associated quality of life, and thus strongly supports a role for IMRT in squamous-cell carcinoma of the head and neck. Funding Cancer Research UK (CRUK/03/005).

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(10)70290-4.pdf

Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial.

This systematic review aimed to assess the literature for prevalence, severity, and impact on quality of life of salivary gland hypofunction and xerostomia induced by cancer therapies. The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. Two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results and conclusions for each article. The inclusion criteria were met by 184 articles covering salivary gland hypofunction and xerostomia induced by conventional, 3D conformal radiotherapy or intensity-modulated radiotherapy in head and neck cancer patients, cancer chemotherapy, total body irradiation/hematopoietic stem cell transplantation, radioactive iodine treatment, and immunotherapy. Salivary gland hypofunction and xerostomia are induced by radiotherapy in the head and neck region depending on the cumulative radiation dose to the gland tissue. Treatment focus should be on optimized/new approaches to further reduce the dose to the parotids, and particularly submandibular and minor salivary glands, as these glands are major contributors to moistening of oral tissues. Other cancer treatments also induce salivary gland hypofunction, although to a lesser severity, and in the case of chemotherapy and immunotherapy, the adverse effect is temporary. Fields of sparse literature included pediatric cancer populations, cancer chemotherapy, radioactive iodine treatment, total body irradiation/hematopoietic stem cell transplantation, and immunotherapy.

A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: prevalence, severity and impact on quality of life

Evidence behind use of intensity modulated radiotherapy: a systematic review of comparative clinical studies (vol 9, pg 367, 2008)

Purpose The purpose of this study was to compare intensity-modulated radiation therapy (IMRT) and three-dimensional conventional radiotherapy (3D-CRT) with regard to patient-rated xerostomia, Radiation Therapy Oncology Group (RTOG) acute and late xerostomia and health-related quality of life (HRQoL) among patients with head and neck squamous cell carcinoma (HNSCC). Methods and Materials Included were 241 patients with HNSCC treated with bilateral irradiation ± chemotherapy. Since 2000, all patients treated with HNSCC were included in a program, which prospectively assessed acute and late morbidity according to the RTOG and HRQoL on a routine basis at regular intervals. Before October 2004, all patients were treated with 3D-CRT ( N = 150). After clinical implementation in October 2004, 91 patients received IMRT. In this study, the differences regarding RTOG toxicity, xerostomia, and other items of HRQoL were analyzed. Results The use of IMRT resulted in a significant reduction of the mean dose of the parotid glands (27 Gy vs. 43 Gy ( p Conclusions IMRT results in a significant reduction of patient- and observer-rated xerostomia, as well as other head and neck symptoms, compared with standard 3D-CRT. These differences translate into a significant improvement of the more general dimensions of HRQoL.

Intensity-modulated radiotherapy reduces radiation-induced morbidity and improves health-related quality of life: results of a nonrandomized prospective study using a standardized follow-up program.

Since its introduction more than a decade ago, intensity-modulated radiotherapy (IMRT) has spread to most radiotherapy departments worldwide for a wide range of indications. The technique has been rapidly implemented, despite an incomplete understanding of its advantages and weaknesses, the challenges of IMRT planning, delivery, and quality assurance, and the substantially increased cost compared with non-IMRT. Many publications discuss the theoretical advantages of IMRT dose distributions. However, the key question is whether the use of IMRT can be exploited to obtain a clinically relevant advantage over non-modulated external-beam radiation techniques. To investigate which level of evidence supports the routine use of IMRT for various disease sites, we did a review of clinical studies that reported on overall survival, disease-specific survival, quality of life, treatment-induced toxicity, or surrogate endpoints. This review shows evidence of reduced toxicity for various tumour sites by use of IMRT. The findings regarding local control and overall survival are generally inconclusive.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(08)70098-6.pdf

Evidence behind use of intensity-modulated radiotherapy: a systematic review of comparative clinical studies.

Purpose: To assess the benefit of intensity-modulated radiotherapy (IMRT) compared with conventional RT for the quality of life (QOL) of head and neck cancer survivors. Methods and Materials: Cross-sectional QOL measures (European Organization for Research and Treatment of Cancer QOL questionnaire C30 and head and neck cancer module) were used with a French multicenter cohort of patients cured of head and neck cancer (follow-up ≥ 1 year) who had received bilateral neck RT (≥ 45 Gy) as a part of their initial treatment. We compared the QOL mean scores regarding RT modality (conventional RT vs. IMRT). The patients of the two groups were matched (one to one) according to the delay between the end of RT and the timing of the QOL evaluation and the T stage. Each QOL item was divided into two relevant levels of severity: "not severe" (responses, "not at all" and "a little") vs. "severe" (responses "quite a bit" and "very much"). The association between the type of RT and the prevalence of severe symptoms was approximated, through multivariate analysis using the prevalence odds ratio. Results: Two comparable groups (67 pairs) were available. Better scores were observed on the head and neck cancer module QOL questionnaire for the IMRT group, especially for dry mouth and sticky saliva ( p p = 0.04) for dry mouth, 3.16 ( p = 0.02) for sticky saliva, 3.58 ( p = 0.02) for pain in the mouth, 3.35 ( p = 0.04) for pain in the jaw, 2.60 ( p = 0.02) for difficulties opening the mouth, 2.76 ( p = 0.02) for difficulties with swallowing, and 2.68 ( p = 0.03) for trouble with eating. Conclusion: The QOL assessment of head and neck cancer survivors demonstrated the benefit of IMRT, particularly in the areas of salivary dysfunction and oral discomfort.

Impact of Intensity-Modulated Radiotherapy on Health-Related Quality of Life for Head and Neck Cancer Patients: Matched-Pair Comparison with Conventional Radiotherapy

Purpose: Our aim was to determine the dose to the clinical target volume (CTV) required for solitary extramedullary plasmacytoma (EMP) in the head and neck (HN). Methods and Materials: Seventeen patients (15 Stage I and 2 Stage II) were treated for HN EMP at our institution between 1979 and 2003. The mean International Commission on Radiation Units (ICRU) dose prescribed to the CTV was 52.6 Gy (range, 40–65 Gy) over 24 fractions (range: 20–30). The Stage II patients received neck irradiation doses of 40 and 60 Gy. A mean dose of 36.4 Gy was used for 5 Stage I patients who received elective neck irradiation. Dose administrated to the CTV was evaluated from dosimetric data or from planning films when dosimetric data were not available. Two groups of patients were distinguished: CTV covered with a dose greater than 40 Gy and CTV covered with a dose greater than 45 Gy. Results: The 5-year local control was 72.8%. It was 100% for patients who received dose to the CTV ≤ 45 Gy vs. 50% for dose to the CTV p = 0.034). The prognostic factor for 5-year disease-specific survival (81.6%) was local control ( p = 0.058). The prognostic factors for disease-free survival (64.1%) were monoclonal immunoglobulin secretion ( p = 0.008) and a CTV dose ≤ 45 Gy ( p = 0.056) Conclusions: Local control of EMP in the HN seems to be improved when the dose to the CTV is ≤ 45 Gy. A minimum dose of 45 Gy should be recommended to the CTV.

Radiotherapy for solitary extramedullary plasmacytoma in the head-and-neck region: A dose greater than 45 Gy to the target volume improves the local control

Genomics to select treatment for patients with metastatic breast cancer

Oncological at home-treatment improves patient quality of life and autonomy but requires close watchfulness of adverse events and compliance to treatment. For nearly ten years, pharmaceutical consultations for home-based anticancer oral therapies patients are proposed on medical request in Avignon-Provence Cancer Institute (ICAP). Organizational changes led us to modify this management by integrating dedicated nurses to create an Oral Therapy Unit (OTU).Needs and expectations assessment questionnaires were proposed to healthcare professionals and patients treated by oral therapies. The analysis of these questionnaires allows to set up an OTU, integrating a dedicated nurse, adapted to the expectations of patients and healthcare professionals. About 8 months later, a new evaluation was carried out to assess the impact of this new support for patient care and health professionals' organization.The results of the studies carried out before OTU implementation highlight the importance of multi-professional support for patients from the start of treatment and during the follow-up. With the new OTU pathway, professionals expect a patient course improvement (94%), a better compliance (88%), a therapeutic accidents reduction (81%) and an improvement in the patient-caregiver relationship (69%). Regarding the organization, 56% of them are expecting to save medical and pharmaceutical time.The OTU creation in our institution and these new multi-professionals' teams' management of patients has obtained a favourable opinion from healthcare professionals and patient satisfaction. 

Alice Mege

Papers

Impact of Intensity-Modulated Radiotherapy on Health-Related Quality of Life for Head and Neck Cancer Patients: Matched-Pair Comparison with Conventional Radiotherapy

Radiotherapy for solitary extramedullary plasmacytoma in the head-and-neck region: A dose greater than 45 Gy to the target volume improves the local control

Genomics to select treatment for patients with metastatic breast cancer

[Improving healthcare organization of patients treated by anticancer oral therapy: What expectations?]