Reirradiation versus systemic therapy versus combination therapy for recurrent high-grade glioma: a systematic review and meta-analysis of survival and toxicity.

PURPOSE: This review compares reirradiation (reRT), systemic therapy and combination therapy (reRT & systemic therapy) with regards to overall survival (OS), progression-free survival (PFS), adverse effects (AEs) and quality of life (QoL) in patients with recurrent high-grade glioma (rHGG). METHODS: A search was performed on PubMed, Scopus, Embase and CENTRAL. Studies reporting OS, PFS, AEs and/or QoL and encompassing the following groups were included; reirradiation vs systemic therapy, combination therapy vs systemic therapy, combination therapy vs reRT, and bevacizumab-based combination therapy vs reRT with/without non-bevacizumab-based systemic therapy. Meta-analyses were performed utilising a random effects model. Certainty of evidence was assessed using GRADE. RESULTS: Thirty-one studies (three randomised, twenty-eight non-randomised) comprising 2084 participants were included. In the combination therapy vs systemic therapy group, combination therapy improved PFS (HR 0.57 (95% CI 0.41-0.79); low certainty) and OS (HR 0.73 (95% CI 0.56-0.95); low certainty) and there was no difference in grade 3 + AEs (RR 1.03 (95% CI 0.57-1.86); very low certainty). In the combination therapy vs reRT group, combination therapy improved PFS (HR 0.52 (95% CI 0.38-0.72); low certainty) and OS (HR 0.69 (95% CI 0.52-0.93); low certainty). In the bevacizumab-based combination therapy vs reRT with/without non-bevacizumab-based systemic therapy group, adding bevacizumab improved PFS (HR 0.46 (95% CI 0.27-0.77); low certainty) and OS (HR 0.42 (95% CI 0.24-0.72; low certainty) and reduced radionecrosis (RR 0.17 (95% CI 0.06-0.48); low certainty). CONCLUSIONS: Combination therapy may improve OS and PFS with acceptable toxicities in patients with rHGG compared to reRT or systemic therapy alone. Particularly, combining bevacizumab with reRT prophylactically reduces radionecrosis. REGISTRATION: CRD42022291741.

Prognostic significance of pre-treatment neutrophil-to-lymphocyte ratio (NLR) in patients with oropharyngeal cancer treated with radiotherapy.

BACKGROUND: This study aimed to evaluate the prognostic value of pre-treatment NLR in patients with oropharyngeal cancer. METHODS: Patients who completed definitive radiotherapy (RT) for oropharyngeal cancer and had blood counts taken pre-RT from 2002 to 2013 were included. NLR was calculated as total neutrophil/lymphocytes. Survival rates were estimated using the Kaplan-Meier method. Univariable and multivariable analyses were conducted with linear and Cox regression methods. NLR was analysed posteriori and dichotomised on the discovered median. RESULTS: Eight hundred and forty-eight patients were analysed. The median pre-RT NLR was 3. Patients with NLR of <3 had improved overall survival (OS) than those with NLR ≥ 3 (5-year OS 85 vs 74%, p < 0.0001). OS differences remained significant when stratified according to HPV status (HPV-positive p = 0.011; HPV-negative p = 0.003). Freedom from any recurrence (FFR), locoregional control (LRC) and freedom of distant recurrence (FDR) were better in those with NLR < 3. The negative impact of elevated pre-RT NLR on OS (HR = 1.64, p = 0.001), FFR (HR = 1.6, p = 0.006) and LRC (HR = 1.8, p = 0.005) remained significant on multivariable analysis. CONCLUSIONS: Pre-RT NLR is an independent prognostic factor in patients with oropharyngeal cancer regardless of HPV status. Patients with lower NLR had more favourable OS and disease control.

Role of Radiation Therapy in Gastric Cancer.

The only curative treatment for localised gastric cancer is surgical resection. However, survival outcomes post-surgery alone remain poor, particularly in those with node-positive disease with 5-year survival of approximately 30%. Therefore, additional perioperative treatment strategies such as radiotherapy and/or chemotherapy have been explored to improve survival outcomes. Early studies established the role of postoperative radiotherapy in improving locoregional control. However, there are now several adjuvant treatment options available, with many centres favouring perioperative chemotherapy. The delivery of radiotherapy in the postoperative setting can be challenging, thereby resulting in suboptimal patient compliance. Hence, the role of preoperative radiotherapy is currently being evaluated. This review focuses on and summarises the landmark clinical trials that have established the current role of radiation therapy in patients with resectable gastric and gastroesophageal adenocarcinoma, and highlights the potential for preoperative radiotherapy.

Vocal-cord Only vs. Complete Laryngeal radiation (VOCAL): a randomized multicentric Bayesian phase II trial.

BACKGROUND: Radiotherapy, along with laser surgery, is considered a standard treatment option for patients with early glottic squamous cell cancer (SCC). Historically, patients have received complete larynx radiotherapy (CL-RT) due to fear of swallowing and respiratory laryngeal motion and this remains the standard approach in many academic institutions. Local control (LC) rates with CL-RT have been excellent, however this treatment can carry significant toxicities include adverse voice and swallowing outcomes, along with increased long-term risk of cerebrovascular morbidity. A recent retrospective study reported improved voice quality and similar local control outcomes with focused vocal cord radiotherapy (VC-RT) compared to CL-RT. There is currently no prospective evidence on the safety of VC-RT. The primary objective of this Bayesian Phase II trial is to compare the LC of VC-RT to that of CL-RT in patients with T1N0 glottic SCC. METHODS: One hundred and fifty-five patients with T1a-b N0 SCC of the true vocal cords that are n ot candidate or declined laser surgery, will be randomized in a 1:3 ratio the control arm (CL-RT) and the experimental arm (VC-RT). Randomisation will be stratified by tumor stage (T1a/T1b) and by site (each site will be allowed to select one preferred radiation dose regimen, to be used in both arms). CL-RT volumes will correspond to the conventional RT volumes, with the planning target volume extending from the top of thyroid cartilage lamina superiorly to the bottom of the cricoid inferiorly. VC-RT volumes will include the involved vocal cord(s) and a margin accounting for respiration and set-up uncertainty. The primary endpoint will be LC at 2-years, while secondary endpoints will include patient-reported outcomes (voice impairment, dysphagia and symptom burden), acute and late toxicity radiation-induced toxicity, overall survival, progression free survival, as well as an optional component of acoustic and objective measures of voice analysis using the Consensus Auditory-Perceptual Evaluation of Voice. DISCUSSION: This study would constitute the first prospective evidence on the efficacy and safety of VC-RT in early glottic cancer. If positive, this study would result in the adoption of VC-RT as standard approach in early glottic cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03759431 Registration date: November 30, 2018.

Surveillance imaging for patients with head and neck cancer treated with definitive radiotherapy: A partially observed Markov decision process model.

BACKGROUND: A possible surveillance model for patients with head and neck cancer (HNC) who received definitive radiotherapy was created using a partially observed Markov decision process. The goal of this model is to guide surveillance imaging policies after definitive radiotherapy. METHODS: The partially observed Markov decision process model was formulated to determine the optimal times to scan patients. Transition probabilities were computed using a data set of 1508 patients with HNC who received definitive radiotherapy between the years 2000 and 2010. Kernel density estimation was used to smooth the sample distributions. The reward function was derived using cost estimates from the literature. Additional model parameters were estimated using either data from the literature or clinical expertise. RESULTS: When considering all forms of relapse, the model showed that the optimal time between scans was longer than the time intervals used in the institutional guidelines. The optimal policy dictates that there should be less time between surveillance scans immediately after treatment compared with years after treatment. Comparable results also held when only locoregional relapses were considered as relapse events in the model. Simulation results for the inclusive relapse cases showed that <15% of patients experienced a relapse over a simulated 36-month surveillance program. CONCLUSIONS: This model suggests that less frequent surveillance scan policies can maintain adequate information on relapse status for patients with HNC treated with radiotherapy. This model could potentially translate into a more cost-effective surveillance program for this group of patients.

Usefulness of surveillance imaging in patients with head and neck cancer who are treated with definitive radiotherapy.

BACKGROUND: The current study was performed to assess the efficacy of surveillance imaging in patients with head and neck cancer (HNC) who are treated definitively with radiotherapy. METHODS: Eligible patients included those with a demonstrable disease-free interval (≥1 follow-up imaging procedure without evidence of disease and a subsequent visit/imaging procedure) who underwent treatment of HNC from 2000 through 2010. RESULTS: A total of 1508 patients were included. The median overall survival was 99 months, with a median imaging follow-up period of 59 months. Of the 1508 patients, 190 patients (12.6%) experienced disease recurrence (107 patients had locoregional and 83 had distant disease recurrence). A total of 119 patients (62.6%) in the group with disease recurrence were symptomatic and/or had an adverse clinical finding associated with the recurrence. Approximately 80% of patients with locoregional disease recurrences presented with a clinical finding, whereas 60% of distant disease recurrences were detected by imaging in asymptomatic patients. Despite the earlier detection of disease recurrence via imaging, those patients in the group of patients with clinically detected disease recurrence were significantly more likely to undergo salvage therapy compared with those whose recurrence was detected on imaging (odds ratio, 0.35). There was no difference in overall survival noted between those patients with disease recurrences that were detected clinically or with imaging alone. Approximately 70% of disease recurrences occurred within the first 2 years. In those patients who developed disease recurrence after 2 years, the median time to recurrence was 51 months. After 2 years, the average number of imaging procedures per patient for the detection of a salvageable recurrence for the imaging-detected group was 1539. CONCLUSIONS: Surveillance imaging in asymptomatic patients with HNC who are treated definitively with radiotherapy without clinically suspicious findings beyond 2 years has a low yield and a high cost. Physicians ordering these studies must use judicious consideration and discretion.

Outcome of patients with early-stage follicular lymphoma staged with 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) and treated with radiotherapy alone.

PURPOSE/OBJECTIVE(S): To evaluate the impact of positron emission tomography (PET) staging on overall survival (OS) and progression-free survival (PFS) in patients with early-stage (stages I and II) follicular lymphoma (ESFL) treated with radiation therapy alone. MATERIALS/METHODS: Eighty-five patients with ESFL treated with curative-intent radiation therapy (RT) between December 2000 and May 2011 were identified. Of those, 13 who had no PET staging and 25 who received additional systemic therapy were excluded from the analysis. Thus, we analyzed 47 patients with PET-staged ESFL treated with definitive radiation therapy alone (dose > 23Gy). Tumour features, pre-treatment computed tomography (CT) and PET stage, dose fractionation, and radiation therapy field extent were recorded. The Kaplan-Meier method was used to estimate the OS and PFS. Patterns of failure were assessed as cumulative incidences assuming competing risks. RESULTS: Median age was 57 years (range 24-83); 43% were females. Most were PET stage 1 (76.6%). Median maximum nodal diameter was 3 cm. Median pre-treatment lactate dehydrogenase (LDH) was 327.5 (range 123-607, upper normal limit = 220). Twenty-six patients (55.3%) had infra-diaphragmatic disease. All received 30-36Gy in 15-24 fractions, with 59.6% treated with involved-field radiation therapy (IFRT) techniques. There was no significant difference in PFS between CT stage I and stage II (HR 1.30 95% CI [0.25-6.72], p = 0.75) with a 5-year PFS of 77% and 78% respectively. However, stage I on PET staging had a significantly better PFS than stage II (HR 4.66 95% CI [1.15-18.8], p = 0.038), with 5-year PFS of 84% and 60% respectively. Ten patients had recurrent disease, with distant disease being the first site of failure in seven patients. Seven-year OS was 91% (95% CI 79-100) for the whole cohort. CONCLUSION: FDG-PET should be considered an essential element in the evaluation of patients with ESFL being considered for RT.

Outcomes of patients diagnosed with carcinoma metastatic to the neck from an unknown primary source and treated with intensity-modulated radiation therapy.

BACKGROUND: There are few published studies to guide the treatment of carcinoma metastatic to the neck from an unknown primary (CUP). In this regard, the objective of the current study was to share the authors' current experience treating patients with CUP using intensity-modulated radiation therapy (IMRT), which principally targeted both sides of the neck, the nasopharynx, and the oropharynx. METHODS: This was a retrospective study in which an institutional database search was conducted to identify patients with CUP who received IMRT. Data analysis included frequency tabulation, survival analysis, and multivariable analysis. RESULTS: Two-hundred sixty patients met inclusion criteria. The most common lymph node category was N2b (54%). IMRT volumes included the entire pharyngolaryngeal mucosa in 78 patients, the nasopharynx and oropharynx in 167 patients, and treatment limited to the involved neck in 11 patients. Eighty-four patients underwent neck dissections. The 5-year overall survival, regional control, and distant metastases-free survival rates were 84%, 91%, and 94%, respectively. Over 40% of patients had gastrostomy tubes during therapy, and 7% patients were diagnosed with chronic radiation-associated dysphagia. Higher lymph node burden was associated with worse disease-related outcomes, and in subgroup analysis, patients with human papillomavirus-associated disease had better outcomes. No therapeutic modality was statistically associated with either disease-related outcomes or toxicity. CONCLUSIONS: Comprehensive IMRT with treatment to both sides of the neck and to the oropharyngeal and nasopharyngeal mucosa results in high rates of disease control and survival. The investigators were unable to demonstrate that treatment intensification with chemotherapy or surgery added benefit or excessive toxicity. Cancer 2018;124:1415-27. © 2018 American Cancer Society.

Predicting treatment Response based on Dual assessment of magnetic resonance Imaging kinetics and Circulating Tumor cells in patients with Head and Neck cancer (PREDICT-HN): matching 'liquid biopsy' and quantitative tumor modeling.

BACKGROUND: Magnetic resonance imaging (MRI) has improved capacity to visualize tumor and soft tissue involvement in head and neck cancers. Using advanced MRI, we can interrogate cell density using diffusion weighted imaging, a quantitative imaging that can be used during radiotherapy, when diffuse inflammatory reaction precludes PET imaging, and can assist with target delineation as well. Correlation of circulating tumor cells (CTCs) measurements with 3D quantitative tumor characterization could potentially allow selective, patient-specific response-adapted escalation or de-escalation of local therapy, and improve the therapeutic ratio, curing the greatest number of patients with the least toxicity. METHODS: The proposed study is designed as a prospective observational study and will collect pretreatment CT, MRI and PET/CT images, weekly serial MR imaging during RT and post treatment CT, MRI and PET/CT images. In addition, blood sample will be collected for biomarker analysis at those time intervals. CTC assessments will be performed on the CellSave tube using the FDA-approved CellSearch® Circulating Tumor Cell Kit (Janssen Diagnostics), and plasma from the EDTA blood samples will be collected, labeled with a de-identifying number, and stored at - 80 °C for future analyses. DISCUSSION: The primary objective of the study is to evaluate the prognostic value and correlation of weekly tumor response kinetics (gross tumor volume and MR signal changes) and circulating tumor cells of mucosal head and neck cancers during radiation therapy using MRI in predicting treatment response and clinical outcomes. This study will provide landmark information as to the utility of CTCs ('liquid biopsy) and tumor-specific functional quantitative imaging changes during treatment to guide personalization of treatment for future patients. Combining the biological information from CTCs and the structural information from MRI may provide more information than either modality alone. In addition, this study could potentially allow us to determine the optimal time to obtain MR imaging and/ or CTCs during radiotherapy to assess tumor response and provide guidance for patient selection and stratification for future dose escalation or de-escalation strategies. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT03491176 ). Date of registration: 9th April 2018. (retrospectively registered). Date of enrolment of the first participant: 30th May 2017.

Narrative review of the utility of magnetic resonance imaging in radiotherapy for cervical cancer.

BACKGROUND AND OBJECTIVE: In radiotherapy (RT) for locally advanced cervical cancer, high soft tissue contrast on magnetic resonance imaging (MRI) can ensure accurate delineation of target volumes (TVs) and optimal dose distribution to the RT target and organs at risk (OAR). MRI-guided adaptive RT (MRIgART) is a novel technology that revises RT plans according to anatomical changes occurring throughout the treatment to improve target coverage and minimise OAR toxicity. This review aims to assess the evidence and gaps of MRI use in RT planning and MRIgART in the treatment of cervical cancer, as well as challenges in its clinical implementation. METHODS: Ovid Medline and PubMed were searched using keywords for MRI in RT for cervical cancer. After applying the inclusion and exclusion criteria, the initial search was deduced to 32 studies. A total of 37 final studies were reviewed, including eight additional articles from references. KEY CONTENT AND FINDINGS: In the primary studies, TVs and organ motion were assessed before, during, and after treatment. MRI was used to investigate dose distribution and therapeutic response to the treatment in association with its outcome. Lastly, rationales for MRIgART were evaluated. CONCLUSIONS: It was concluded that MRI enables accurate target delineation, assessment of organ motion and interfraction changes, and monitoring of treatment response through dynamic parameters. Enhanced target coverage and reduced OAR irradiation through MRIgART can improve local control and the overall outcome, although its rationales against the logistical challenges need to be evaluated on further research.

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.

The impact of fluorine-18-fluoroethyltyrosine positron emission tomography scan timing on radiotherapy planning in newly diagnosed patients with glioblastoma.

Background and purpose: Glioblastoma is one of the most common and aggressive primary brain tumours in adults. Though radiation therapy (RT) techniques have progressed significantly in recent decades, patient survival has seen little improvement. However, an area of promise is the use of fluorine-18-fluoroethyltyrosine positron-emission-tomography (18F-FET PET) imaging to assist in RT target delineation. This retrospective study aims to assess the impact of 18F-FET PET scan timing on the resultant RT target volumes and subsequent RT plans in post-operative glioblastoma patients. Materials and Methods: The imaging and RT treatment data of eight patients diagnosed with glioblastoma and treated at a single institution were analysed. Before starting RT, each patient had two 18F-FET-PET scans acquired within seven days of each other. The information from these 18F-FET-PET scans aided in the creation of two novel target volume sets. The new volumes and plans were compared with each other and the originals. Results: The median clinical target volume (CTV) 1 was statistically smaller than CTV 2. The median Dice score for the CTV1/CTV2 was 0.98 and, of the voxels that differ (median 6.5 cc), 99.7% were covered with a 5 mm expansion. Overall organs at risk (OAR) and target dosimetry were similar in the PTV1 and PTV2 plans. Conclusion: Provided the 18F-FET PET scan is acquired within two weeks of the RT planning and a comprehensive approach is taken to CTV delineation, the timing of scan acquisition has minimal impact on the resulting RT plan.

Safety and tolerability of radiotherapy in combination with systemic targeted therapies for treatment of hepatocellular carcinoma: a narrative review.

BACKGROUND AND OBJECTIVE: Palliative radiotherapy (RT) and systemic immuno- or targeted therapy both play significant roles in the treatment of advanced hepatocellular carcinoma (HCC). Concurrent application of these therapies is increasing, however, no guidelines exist regarding the combination of systemic therapy with RT. This narrative review summarises the existing literature reporting toxicity observed after concurrent treatment with RT and immuno- or targeted therapeutic agents commonly used in HCC. METHODS: The PubMed database was searched for studies published between 2011 and 2023 reporting toxicity data on patients treated concurrently with RT and targeted agents used in HCC. Due to the paucity of relevant literature in HCC, the inclusion criteria were expanded to include non-HCC cohorts treated with targeted therapies commonly used in advanced HCC. KEY CONTENT AND FINDINGS: Sixty-seven articles were included in this review. Twenty-two articles reported combined RT with sorafenib, one with regorafenib, 22 with bevacizumab, three with lenvatinib and 19 with immune checkpoint inhibitors. Significant findings include a high rate severe hepatotoxicity with combination RT and sorafenib, ranging from 0-19% with liver stereotactic body radiotherapy (SBRT) and 3-18% with conventionally fractionated liver RT. Severe gastrointestinal (GI) toxicities including perforation and ulceration were seen with combination bevacizumab and RT, ranging from 0-27% in the acute setting and 0-23% in the late setting. The safety profile of combination immune checkpoint blockade agents and RT was similar to that seen in monotherapy. CONCLUSIONS: Existing data suggests that combination RT and targeted therapy given the risk of severe adverse events including hepatotoxicity and GI toxicity. There is an urgent need for future studies specifically examining the impact of combination therapy in HCC patients to guide clinical decision-making in the evolving landscape of immune- and targeted therapies.

Stereotactic Body Radiotherapy as a Curative Treatment for De Novo Mucosal Carcinoma of the Head and Neck: A Feasible Alternative Option for Fragile Patients with Small Lesion: A Systematic Review.

Stereotactic body radiotherapy (SBRT) is characterized by a high dose per fraction, well-defined small targets, superior dose conformity, and a steep off-target dose gradient. A literature search was conducted to examine the experience with SBRT as a curative treatment for newly diagnosed mucosal carcinoma of the head and neck (MCHN). Four retrospective case series and one prospective phase I clinical trial published between 2012 and 2020 described 124 patients. SBRT was mainly performed in older patients with different tumor sites. The median size of the planning target volumes ranged from 5.3 to 41 cm3. Different approaches were used to create margins. In two studies, limited elective nodal irradiation was performed. The equivalent doses used were 60-83.33 Gy delivered in five fractions. Considerable heterogeneity was observed in the radiation dose specification. The incidence of grade ≥3 late toxicity was 0-8.3%, with local and regional control ranging from 73% to 100%. Improved or stable quality of life after SBRT was reported in two studies. Curative-intent SBRT for de novo MCHN appears to be an effective and relatively safe treatment for small tumor targets, preferably without concomitant elective tissue irradiation. Standardization of SBRT practice and well-designed prospective clinical trials are needed to better define the role of SBRT in this setting.

Stabilised Hyaluronic Acid (sHA) gel as a novel marker for breast cancer tumour bed cavity: Surgical feasibility.

Introduction: Consistent delineation of the breast conserving surgery (BCS) tumour bed (TB) for breast cancer remains a challenge for radiation oncologists. Accurate delineation allows for better local control and reduces toxicity when planning partial breast or TB boost radiation therapy (RT). Methods: In the operating theatre (OT) breast surgeons inserted stabilised hyaluronic acid (sHA) gel as small drops approximately one cm into the walls surrounding the resection cavity. Surgical feasibility was determined by the rate of successful sHA gel insertion procedure, the ease of insertion as rated by surgeons, the time required for insertion procedure, the quantity used, and any adverse events (AE) relating to sHA gel insertion. Results: Thirty-five patients were enrolled. All patients underwent sHA gel insertion successfully. The procedure added a median of 2.8 min to the OT time and was rated as 'easy' in 89 % of patients. There were no immediate AE in OT. Five (14 %) patients experienced a grade 2 or higher AE. Three of the five patients were prescribed oral antibiotics for breast infection. Two of the five patients experienced a grade 3 AE - haematoma which required evacuation in OT day 1 post-BCS, and infected seroma which required drainage and washout in OT 2 months post-BCS. All five patients recovered and underwent the planned adjuvant therapies for their BC. The AE data reflects common risks with standard BCS and are not clearly attributed to sHA gel insertion alone. Conclusion: We show that sHA gel is surgically feasible as a marker to help define the TB cavity for post-BCS adjuvant MRI-based RT planning.

Neurological complications of modern radiotherapy for head and neck cancer.

Radiotherapy is one of the mainstay treatment modalities for the management of non-metastatic head and neck cancer (HNC). Notable improvements in treatment outcomes have been observed in the recent decades. Modern radiotherapy techniques, such as intensity-modulated radiotherapy and charged particle therapy, have significantly improved tumor target conformity and enabled better preservation of normal structures. However, because of the intricate anatomy of the head and neck region, multiple critical neurological structures such as the brain, brainstem, spinal cord, cranial nerves, nerve plexuses, autonomic pathways, brain vasculature, and neurosensory organs, are variably irradiated during treatment, particularly when tumor targets are in close proximity. Consequently, a diverse spectrum of late neurological sequelae may manifest in HNC survivors. These neurological complications commonly result in irreversible symptoms, impair patients' quality of life, and contribute to a substantial proportion of non-cancer deaths. Although the relationship between radiation dose and toxicity has not been fully elucidated for all complications, appropriate application of dosimetric constraints during radiotherapy planning may reduce their incidence. Vigilant surveillance during the course of survivorship also enables early detection and intervention. This article endeavors to provide a comprehensive review of the various neurological complications of modern radiotherapy for HNC, summarize the current incidence data, discuss methods to minimize their risks during radiotherapy planning, and highlight potential strategies for managing these debilitating toxicities.

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.

Patterns of failure for recurrent head and neck squamous cell carcinoma treated with salvage surgery and postoperative IMRT reirradiation.

Purpose/Objectives: The purpose of this study was to evaluate patterns of locoregional recurrence (LRR) after surgical salvage and adjuvant reirradiation with IMRT for recurrent head and neck squamous cell cancer (HNSCC). Materials/Methods: Patterns of LRR for 61 patients treated consecutively between 2003 and 2014 who received post-operative IMRT reirradiation to ≥ 60 Gy for recurrent HNSCC were determined by 2 methods: 1) physician classification via visual comparison of post-radiotherapy imaging to reirradiation plans; and 2) using deformable image registration (DIR). Those without evaluable CT planning image data were excluded. All recurrences were verified by biopsy or radiological progression. Failures were defined as in-field, marginal, or out-of-field. Logistic regression analyses were performed to identify predictors for LRR. Results: A total of 55 patients were eligible for analysis and 23 (42 %) had documented LRR after reirradiation. Location of recurrent disease prior to salvage surgery (lymphatic vs. mucosal) was the most significant predictor of LRR after post-operative reirradiation with salvage rate of 67 % for lymphatic vs. 33 % for mucosal sites (p = 0.037). Physician classification of LRR yielded 14 (61 %) in-field failures, 3 (13 %) marginal failures, and 6 (26 %) out-of-field failures, while DIR yielded 10 (44 %) in-field failures, 4 (17 %) marginal failures, and 9 (39 %) out-of-field failures. Most failures (57 %) occurred within the original site of recurrence or first echelon lymphatic drainage. Of patients who had a free flap placed during salvage surgery, 56 % of failures occurred within 1 cm of the surgical flap. Conclusion: Our study highlights the role of DIR in enhancing the accuracy and consistency of POF analysis. Compared to traditional visual inspection, DIR reduces interobserver variability and provides more nuanced insights into dose-specific and spatial parameters of locoregional recurrences. Additionally, the study identifies the location of the initial recurrence as a key predictor of subsequent locoregional recurrence after salvage surgery and re-IMRT.

Molecularly defined sinonasal malignancies: an overview with focus on the current WHO classification and recently described provisional entities.

Classification of tumors of the head and neck has evolved in recent decades including a widespread application of molecular testing in tumors of the sinonasal tract, salivary glands, and soft tissues with a predilection for the head and neck. The availability of new molecular techniques has allowed for the definition of multiple novel tumor types unique to head and neck sites. Moreover, an expanding spectrum of immunohistochemical markers specific to genetic alterations facilitates rapid identification of diagnostic molecular abnormalities. As such, it is currently possible for head and neck pathologists to benefit from a molecularly defined tumor classification while making diagnoses that are still based largely on histopathology and immunohistochemistry. This review covers the principal molecular alterations in sinonasal malignancies, such as alterations in DEK, AFF2, NUTM1, IDH1-2, and SWI/SNF genes in particular, that are important from a practical standpoint for diagnosis, prognosis, and prediction of response to treatment.

Stereotactic Body Radiotherapy in Recurrent and Oligometastatic Head and Neck Tumours.

The treatment of head and neck cancers (HNCs) encompasses a complex paradigm involving a combination of surgery, radiotherapy, and systemic treatment. Locoregional recurrence is a common cause of treatment failure, and few patients are suitable for salvage surgery. Reirradiation with conventional radiation techniques is challenging due to normal tissue tolerance limits and the risk of significant toxicities. Stereotactic body radiotherapy (SBRT) has emerged as a highly conformal modality that offers the potential for cure while limiting the dose to surrounding tissue. There is also growing research that shows that those with oligometastatic disease can benefit from curative intent local ablative therapies such as SBRT. This review will look at published evidence regarding the use of SBRT in locoregional recurrent and oligometastatic HNCs.