Adaptive radiotherapy for head and neck cancer: Pitfalls and possibilities from the radiation oncologist's point of view.

BACKGROUND: Patients with head and neck cancer (HNC) may experience substantial anatomical changes during the course of radiotherapy treatment. The implementation of adaptive radiotherapy (ART) proves effective in managing the consequent impact on the planned dose distribution. METHODS: This narrative literature review comprehensively discusses the diverse strategies of ART in HNC and the documented dosimetric and clinical advantages associated with these approaches, while also addressing the current challenges for integration of ART into clinical practice. RESULTS AND CONCLUSION: Although based on mainly non-randomized and retrospective trials, there is accumulating evidence that ART has the potential to reduce toxicity and improve quality of life and tumor control in HNC patients treated with RT. However, several questions remain regarding accurate patient selection, the ideal frequency and timing of replanning, and the appropriate way for image registration and dose calculation. Well-designed randomized prospective trials, with a predetermined protocol for both image registration and dose summation, are urgently needed to further investigate the dosimetric and clinical benefits of ART.

Dosimetric parameters predict radiation-induced temporal lobe necrosis in nasopharyngeal carcinoma patients: A systematic review and meta-analysis.

This systematic review examines the role of dosimetric parameters in predicting temporal lobe necrosis (TLN) risk in nasopharyngeal carcinoma (NPC) patients treated with three-dimensional conformal RT (3D-CRT), intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). TLN is a serious late complication that can adversely affect the quality of life of NPC patients. Understanding the relationship between dosimetric parameters and TLN can guide treatment planning and minimize radiation-related complications. A comprehensive search identified relevant studies published up to July 2023. Studies reporting on dosimetric parameters and TLN in NPC patients undergoing 3D-CRT, IMRT, and VMAT were included. TLN incidence, follow-up duration, and correlation with dosimetric parameters of the temporal lobe were analyzed. The review included 30 studies with median follow-up durations ranging from 28 to 110 months. The crude incidence of TLN varied from 2.3 % to 47.3 % and the average crude incidence of TLN is approximately 14 %. Dmax and D1cc emerged as potential predictors of TLN in 3D-CRT and IMRT-treated NPC patients. Threshold values of >72 Gy for Dmax and >62 Gy for D1cc were associated with increased TLN risk. However, other factors should also be considered, including host characteristics, tumor-specific features and therapeutic factors. In conclusion, this systematic review highlights the significance of dosimetric parameters, particularly Dmax and D1cc, in predicting TLN risk in NPC patients undergoing 3D-CRT, IMRT, and VMAT. The findings provide valuable insights that can help in developing optimal treatment planning strategies and contribute to the development of clinical guidelines in this field.

Impact of consensus guidelines on delineation of primary tumor clinical target volume (CTVp) for head and neck cancer: Results of a national review project.

BACKGROUND AND PURPOSE: A significant interobserver variability (IOV) for clinical target volume of the primary tumor (CTVp) delineation was shown in a previous national review project. Since then, international expert consensus guidelines (CG) for the delineation of CTVp were published. The aim of this follow-up study was to 1) objectify the extent of implementation of the CG, 2) assess its impact on delineation quality and consistency, 3) identify any remaining ambiguities. MATERIALS AND METHODS: All Belgian RT departments were invited to complete an online survey and submit CTVp for 5 reference cases. Organs at risk and GTV of the primary tumor were predefined. Margins, volumes, IOV between all participating centers (IOVall) and IOV compared to a reference consensus delineation (IOVref) were calculated and compared to the previous analysis. A qualitative analysis was performed assessing the correct interpretation of the CG for each case. RESULTS: 17 RT centers completed both survey and delineations, of which 88% had implemented CG. Median DSCref for CTVp_total was 0.80-0.92. IOVall and IOVref improved significantly for the centers following CG (p = 0.005). IOVref for CTVp_high was small with a DSC higher than 0.90 for all cases. A significant volume decrease for the CTVp receiving 70 Gy was observed. Interpretation of CG was more accurate for (supra)glottic carcinoma. 60% of the radiation oncologists thinks clarification of CG is indicated. CONCLUSION: Implementation of consensus guidelines for CTVp delineation is already fairly advanced on a national level, resulting in significantly increased delineation uniformity. The accompanying substantial decrease of CTV receiving high dose RT calls for caution and correct interpretation of CG. Clarification of the existing guidelines seems appropriate especially for oropharyngeal and hypopharyngeal carcinoma.

Proton Beam Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma.

Purpose: To discuss the role of proton beam therapy (PBT) in the treatment of patients with oropharyngeal squamous cell carcinoma (OPSCC). Materials and Methods: A review of the pertinent literature. Results: Proton beam therapy likely results in reduced acute and late toxicity as compared with intensity-modulated radiation therapy (IMRT). The extent of the reduced toxicity, which may be modest, depends on the endpoint and technical factors such as pencil beam versus passive scattered PBT and adaptive replanning. The disease control rates after PBT are likely similar to those after IMRT. Conclusion: Proton beam therapy is an attractive option to treat patients with OPSCC. Whether it becomes widely available depends on access.

EffEx-HN trial: study protocol for a randomized controlled trial on the EFFectiveness and feasibility of a comprehensive supervised EXercise program during radiotherapy in Head and Neck cancer patients on health-related quality of life.

BACKGROUND: With over 500,000 annually reported cases worldwide, head and neck cancer (HNC) is the seventh most common type of cancer worldwide. Treatment of HNC with chemoradiotherapy frequently results in serious impairments in physical and psychosocial functioning. Besides, HNC patients typically start their cancer treatment already with poor physical and psychosocial health. It has been shown that a sufficient level of physical activity (PA) before, during, and after cancer treatment is associated with fewer negative treatment-related side effects and a better quality of life (QOL). In order to prevent worsening of functioning and limit the physical impact of the HNC treatment, a comprehensive supervised exercise program (CSEP) may be beneficial during early cancer treatment. However, up to now, the feasibility and effectiveness of such a program are not yet investigated thoroughly in HNC. Therefore, the primary objective of this study is to examine the effectiveness of a CSEP during HNC treatment, in addition to usual supportive care, compared to usual supportive care alone, on health-related QOL up to 1 year post-diagnosis. Secondary objectives entail gathering information on (1) the effectiveness of a CSEP on secondary outcomes such as physical and mental function, activities of daily life, and participation in society and (2) the feasibility, possible barriers, and facilitators for participation in a CSEP during HNC treatment. METHODS: To investigate the effectiveness of the CSEP, a parallel, open-label randomized controlled trial will be performed. To study the feasibility of the CSEP, a mixed-method study will be performed in a subgroup of participants. HNC patients are eligible if they receive radiotherapy at the Radiation-Oncology department of the University Hospital of Leuven. A 4-size permuted block randomization will be used. The control group receives the current standard of supportive care. The intervention group receives a CSEP, additional to the same usual supportive care. The CSEP consists of a 12-week intensive phase with 3 exercise sessions of 1 h per week, where supervision is gradually reduced after 6 weeks. During the maintenance phase (from week 13), patients exercise at home with monthly tele-consultations with a physiotherapist. The CSEP contains supervised aerobic and resistance training. In both groups, outcomes of interest are evaluated through self-reported questionnaires and clinical assessments, at baseline, 6 weeks, 12 weeks, 6 months, and 12 months post-diagnosis. The primary endpoint is health-related QOL, measured with the EORTC QLQ-C30 at 6 months post-diagnosis. DISCUSSION: The study will be conducted in accordance with the Declaration of Helsinki. This protocol has been approved by the ethical committee of the University Hospitals Leuven (s65549). Recruitment started in January 2022. Results will be disseminated via peer-reviewed scientific journals and presentations at congresses. TRIAL REGISTRATION: Trial Registration: ClinicalTrials.gov Identifier: NCT05256238 Date of registration: February 25, 2022.

Benefits of automated gross tumor volume segmentation in head and neck cancer using multi-modality information.

PURPOSE: Gross tumor volume (GTV) delineation for head and neck cancer (HNC) radiation therapy planning is time consuming and prone to interobserver variability (IOV). The aim of this study was (1) to develop an automated GTV delineation approach of primary tumor (GTVp) and pathologic lymph nodes (GTVn) based on a 3D convolutional neural network (CNN) exploiting multi-modality imaging input as required in clinical practice, and (2) to validate its accuracy, efficiency and IOV compared to manual delineation in a clinical setting. METHODS: Two datasets were retrospectively collected from 150 clinical cases. CNNs were trained for GTV delineation with consensus delineation as ground truth, with either single (CT) or co-registered multi-modal (CT + PET or CT + MRI) imaging data as input. For validation, GTVs were delineated on 20 new cases by two observers, once manually, once by correcting the delineations generated by the CNN. RESULTS: Both multi-modality CNNs performed better than the single-modality CNN and were selected for clinical validation. Mean Dice Similarity Coefficient (DSC) for (GTVp, GTVn) respectively between automated and manual delineations was (69%, 79%) for CT + PET and (59%,71%) for CT + MRI. Mean DSC between automated and corrected delineations was (81%,89%) for CT + PET and (69%,77%) for CT + MRI. Mean DSC between observers was (76%,86%) for manual delineations and (95%,96%) for corrected delineations, indicating a significant decrease in IOV (p < 10-5), while efficiency increased significantly (48%, p < 10-5). CONCLUSION: Multi-modality automated delineation of GTV of HNC was shown to be more efficient and consistent compared to manual delineation in a clinical setting and beneficial over a single-modality approach.

Increasing Adherence to Prophylactic Swallowing Exercises During Head and Neck Radiotherapy: The Multicenter, Randomized Controlled PRESTO-Trial.

BACKGROUND: Prophylactic swallowing exercises (PSE) during radiotherapy can significantly reduce dysphagia after radiotherapy in head and neck cancer (HNC). However, its positive effects are hampered by low adherence rates during the burdensome therapy period. Hence, the main goal of this multicenter randomized controlled trial (RCT) was to investigate the effect of 3 different service-delivery modes on actual patients' adherence. METHODS: A total of 148 oropharyngeal cancer patients treated with primary (chemo)radiotherapy were randomly assigned to a 4 weeks PSE program, either diary-supported (paper group; n = 49), app-supported (app group; n = 49) or therapist-supported (therapist group; n = 50). Participants practiced 5 days/week, daily alternating tongue strengthening exercises with chin tuck against resistance exercises. Adherence was measured as the percentage of completed exercise repetitions per week (%reps). Statistical analysis was performed by means of SPSSv27, using Linear Mixed-effects Models with post hoc pairwise testing and Bonferroni-Holm correction. RESULTS: Adherence and evolution of adherence over time was significantly different between the three groups (p < .001). Adherence rates decreased in all three groups during the 4 training weeks (p < .001). During all 4 weeks, the therapist group achieved the highest adherence rates, whilst the app group showed the lowest adherence rates. CONCLUSIONS: PSE adherence decreased during the first 4 radiotherapy weeks regardless of group, but with a significant difference between groups. The therapist group achieved the highest adherence rates with a rather limited decline, therefore, increasing the face-to-face contact with a speech-language therapist can overcome the well-known problem of low adherence to PSE in this population. TRIAL REGISTRATION: Trial registration: ISRCTN, ISRCTN98243550. Registered December 21, 2018 - retrospectively registered, https://www.isrctn.com/ISRCTN98243550?q=gwen%20van%20nuffelen&filters=&sort=&offset=1&totalResults=2&page=1&pageSize=10&searchType=basic-search .

Home-based intensive treatment of chronic radiation-associated dysphagia in head and neck cancer survivors (HIT-CRAD trial).

BACKGROUND: Chronic radiation-associated dysphagia (C-RAD) is considered to be one of the most severe functional impairments in head and neck cancer survivors treated with radiation (RT) or chemoradiation (CRT). Given the major impact of these late toxicities on patients' health and quality of life, there is a strong need for evidence-based dysphagia management. Although studies report the benefit of strengthening exercises, transference of changes in muscle strength to changes in swallowing function often remains limited. Therefore, combining isolated strengthening exercises with functional training in patients with C-RAD may lead to greater functional gains. METHODS: This 3-arm multicenter randomized trial aims to compare the efficacy and possible detraining effects of mere strengthening exercises (group 1) with a combination of strengthening exercises and functional swallowing therapy (group 2) and non-invasive brain stimulation added to that combination (group 3) in 105 patients with C-RAD. Patients will be evaluated before and during therapy and 4 weeks after the last therapy session by means of swallowing-related and strength measures and quality of life questionnaires. DISCUSSION: Overall, this innovative RCT is expected to provide new insights into the rehabilitation of C-RAD to optimize post-treatment swallowing function. TRIAL REGISTRATION: International Standard Randomized Controlled Trials Number (ISRCTN) registry ID ISRCTN57028065. Registration was accepted on 15 July 2021.

Proton Therapy for Squamous Cell Carcinoma of the Head and Neck: Early Clinical Experience and Current Challenges.

Proton therapy (PT) is a promising development in radiation oncology, with the potential to further improve outcomes for patients with squamous cell carcinoma of the head and neck (HNSCC). By utilizing the finite range of protons, healthy tissue can be spared from beam exit doses that would otherwise be irradiated with photon-based treatments. Current evidence on PT for HNSCC is limited to comparative dosimetric analyses and retrospective single-institution series. As a consequence, the recognized indications for the reimbursement of PT remain scarce in most countries. Nevertheless, approximately 100 PT centers are in operation worldwide, and initial experiences for HNSCC are being reported. This review aims to summarize the results of the early clinical experience with PT for HNSCC and the challenges that are currently faced.

Vaginal mucositis in patients with gynaecological cancer undergoing (chemo-)radiotherapy: a retrospective analysis.

The objective of this retrospective analysis was to determine the incidence and extent of vaginal mucositis (VM) in women with gynaecological cancer undergoing external (chemo)radiation therapy (CRT). A retrospective analysis was set up to collect data on the incidence and severity of VM in women treated with external pelvic RT for gynaecological cancer at the Jessa Hospital, Hasselt and ZOL, Genk, BE between January 2017 and June 2018. At the start and end of their external (C)RT, they rated the frequency and intensity of five common symptoms of VM. Thirty-three patients treated with RT for gynaecological cancer met the inclusion criteria. A non-negligible proportion of patients already experienced at least one VM symptom to any degree before the start of RT, a proportion that further increased towards the end of the RT (73%). At the end of RT, on average, about 25% of these patients reported moderate-to-severe symptoms (against about 7% before the (C)RT). These results suggest that VM is a rather frequent side effect in gynaecological cancer patients that aggravates during treatment up to a moderate severity level. Although the small sample size, these data highlight the need for attention to VM.Impact StatementWhat is already known about this topic? Radiotherapy plays an important role in the treatment of gynaecological malignancies. A debilitating complication in patients undergoing pelvic radiotherapy is vaginal mucositis, an inflammation of the vaginal mucosal lining. To date, the incidence of vaginal mucositis is still not well documented.What this paper adds? A non-negligible proportion of patients already experienced at least one symptom related to vaginal mucositis before the start of radiotherapy. Most patients presented mild to moderate vaginal mucositis symptoms at the end of external pelvic radiotherapy. Burning sensation, pruritus, and pain were the most frequently documented radiotherapy-induced complications.The implications of this paper: Vaginal mucositis is an underrated side effect of pelvic radiotherapy that needs to be tackled multidisciplinary by a team of nurses, radiotherapists, oncologists, and gynaecologists. The team should tackle the complication from the start of radiotherapy by using the most appropriate measures. Due to a possible link between acute vaginal mucositis and late vaginal toxicity, the team needs to follow-up patient's post-radiotherapy to support patients in late complications and advise/encourage patients in performing vaginal dilatation to prevent vaginal stenosis.

Radiation Treatment for Inoperable Local Relapse of Parathyroid Carcinoma With Symptomatic Hypercalcemia: A Case Report.

BACKGROUND: Parathyroid carcinoma (PC) is an extremely rare malignancy, characterized by slow progression, frequent recurrences and difficult-to-control hypercalcemia which is typically the main contributor to the morbidity and mortality of these patients. Patients often undergo repeated surgical resections, whether or not in combination with adjuvant radiation treatment. The role of radiation therapy within the symptomatic treatment of PC currently remains unclear. CASE DESCRIPTION: We describe a 30-year-old male patient with an inoperable local relapse of PC and secondary symptomatic hypercalcemia, maximally pharmacologically treated. After a local radiation treatment to a total dose of 70 Gray in 35 fractions serum calcium and parathyroid hormone (PTH) levels decreased, accompanied by improvement of the severe gastro-intestinal disturbances. CONCLUSION: For patients with inoperable symptomatic PC despite maximal medical treatment who are in a good overall condition, radiation treatment can be considered in well-defined cases to decrease symptoms and improve quality of life.

Recurrence Patterns After IMRT/VMAT in Head and Neck Cancer.

PURPOSE: Intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT), two advanced modes of high-precision radiotherapy (RT), have become standard of care in the treatment of head and neck cancer. The development in RT techniques has markedly increased the complexity of target volume definition and accurate treatment delivery. The aim of this study was to indirectly investigate the quality of current TV delineation and RT delivery by analyzing the patterns of treatment failure for head and neck cancer patients in our high-volume RT center. METHODS: Between 2004 and 2014, 385 patients with pharyngeal, laryngeal, and oral cavity tumors were curatively treated with primary RT (IMRT/VMAT). We retrospectively investigated locoregional recurrences (LRR), distant metastases (DM), and overall survival (OS). RESULTS: Median follow-up was 6.4 years (IQR 4.7-8.3 years) during which time 122 patients (31.7%) developed LRR (22.1%) and DM (17.7%). The estimated 2- and 5-year locoregional control was 78.2% (95% CI 73.3, 82.3) and 74.2% (95% CI 69.0, 78.8). One patient developed a local recurrence outside the high-dose volume and five patients developed a regional recurrence outside the high-dose volume. Four patients (1.0%) suffered a recurrence in the electively irradiated neck and two patients had a recurrence outside the electively irradiated neck. No marginal failures were observed. The estimated 2- and 5-year DM-free survival rates were 83.3% (95% CI 78.9, 86.9) and 80.0% (95% CI 75.2, 84.0). The estimated 2- and 5-year OS rates were 73.6% (95% CI 68.9, 77.8) and 52. 6% (95% CI 47.3, 57.6). Median OS was 5.5 years (95% CI 4.5, 6.7). CONCLUSION: Target volume definition and treatment delivery were performed accurately, as only few recurrences occurred outside the high-dose regions and no marginal failures were observed. Research on dose intensification and identification of high-risk subvolumes might decrease the risk of locoregional relapses. The results of this study may serve as reference data for comparison with future studies, such as dose escalation or proton therapy trials.

Unilateral versus bilateral nodal irradiation: Current evidence in the treatment of squamous cell carcinoma of the head and neck.

Cancers of the head and neck region often present with nodal involvement. There is a long-standing convention within the community of head and neck radiation oncology to irradiate both sides of the neck electively in almost all cases to include both macroscopic and microscopic disease extension (so called elective nodal volume). International guidelines for the selection and delineation of the elective lymph nodes were published in the early 2000s and were updated recently. However, diagnostic imaging techniques have improved the accuracy and reliability of nodal staging and as a result, small metastases that used to remain undetected and were thus in the past included in the elective nodal volume, will now be included in high-dose volumes. Furthermore, the elective nodal areas are situated close to the parotid glands, the submandibular glands and the swallowing muscles. Therefore, irradiation of a smaller, more selected volume of the elective nodes could reduce treatment-related toxicity. Several researchers consider the current bilateral elective neck irradiation strategies an overtreatment and show growing interest in a unilateral nodal irradiation in selected patients. The aim of this article is to give an overview of the current evidence about the indications and benefits of unilateral nodal irradiation and the use of SPECT/CT-guided nodal irradiation in squamous cell carcinomas of the head and neck.