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Background and purpose The FiGaRO trial assessed the feasibility and safety of using an FDG-PET-based dose-painting technique to deliver a radiotherapy (RT) boost to the FDG-avid primary tumour in patients with locally advanced high and intermediate risk oropharyngeal cancer. Materials and method Patients underwent a planning 18FDG-PET-CT scan, immobilised in the treatment position, after one cycle of induction chemotherapy. The volume of persistent FDG-avidity in the primary tumour was escalated to 71.5 Gy in30 fractions delivered using a simultaneous integrated boost Intensity Modulated RT (SIB-IMRT) technique. RT was delivered with concomitant Cisplatin following 2 cycles of induction chemotherapy. The primary outcome was the incidence of grade ≥ 3 late mucosal toxicity 12 months post-treatment, with an excess rate of >10% regarded as unacceptable. Results Twenty-nine patients were included and twenty-four were treated between 2014 and 2018, in two UK centres. Median follow-up was 36 months (range 4–56 months). Pre-defined planning target volume objectives and organ at risk dose constraints were met in all cases. There were no incidents of acute grade 4 toxicity. There were 4 cases of grade ≥ 3 mucosal toxicity at 12 months post-treatment (19.1%). There were no cases of persistent mucosal ulceration at 12 months. Overall survival at 3-years was 87.5%, 92.9% for intermediate and 70.0% for high risk patients. Conclusion Late toxicity rates, although higher than anticipated, are comparable to contemporary published data for standard dose chemo-IMRT. Results suggest improved 3y survival rates for high risk patients. This approach merits further investigation. ClinicalTrials.gov Identifier: NCT02953197.

Purpose To evaluate whether the 8th staging system is a better discriminator of overall survival (OS) than the 7th edition for oropharyngeal cancer patients after definitive (chemo)radiotherapy (CRT). Material and methods Data from oropharyngeal cancer patients treated with CRT with curative intent between 2010 and 2016 at Guy’s and St Thomas’ Hospitals were reviewed. Human papillomavirus (HPV) status was ascertained in all cases. Patients were staged using the 7th edition and the 8th edition TNM staging system. Demographics, tumor characteristics and treatment response data were included in univariate and multivariate analysis for OS. OS and disease-free survival (DFS) were estimated using the Kaplan-Meier method. In addition, a multivariate survival Cox regression analysis of several clinical variables was performed. Results A total of 273 patients were included. The median follow-up was 4.7 years. Overall 63 patients died. In multivariate analysis, HPV status, complete response at 3 months and ≤21 units/week alcohol were prognostic for OS. For the entire cohort, the 5-year OS and DFS rates were 78.1% (95% confidence interval CI 0.719–0.831) and 73.9% (95% CI 0.677–0.792), respectively. Better stratification of OS and DFS was recorded by 8th edition for the entire cohort. In HPV-positive cases, risk stratification based on tobacco smoking and nodal stage resulted in statistically higher discrimination in OS rates (5-year OS 90.7% in low risk patients and 84.6% in intermediate risk, p = 0.05) and DFS rates (5-year DFS 91.5% in low risk and 76.1% in intermediate risk, p = 0.001). Conclusion The 8th edition TNM staging system provides better OS stratification in oropharyngeal cancer after definitive CRT compared with the 7th edition. Other clinical variables, such as complete response at 3 months, alcohol and tobacco smoking, should also be considered in future classifications as they provide additional risk stratification information in both HPV-positive and HPV-negative disease.

Objectives To evaluate the ability of post-chemo-radiotherapy (CRT) diffusion-weighted-MRI apparent diffusion coefficient (ADCmean) and 18F-FDG PET maximum standardized uptake value (SUVmax) to predict disease-free survival (DFS) in head and neck squamous cell carcinoma (HNSCC), and to determine whether this ability is influenced by human papillomavirus oropharyngeal cancer (HPV-OPC) status. Methods This prospective cohort observational study included 65 participants (53 male, mean ± SD age 59.9 ± 7.9 years, 46 HPV-OPC) with stage III or IV HNSCC. Primary tumour and nodal ADCmean (pre-treatment, 6- and 12-weeks post-CRT) and SUVmax (12-weeks post-CRT) were measured. Variables were compared with 2-year DFS (independent t-test/Mann–Whitney test) and overall DFS (Cox regression), before and after accounting for HPV-OPC status. Variables were also compared between HPV-OPC and other HNSCC subgroups after stratifying for DFS. Results Absolute post-CRT ADCmean values predicted 2-year DFS and overall DFS for all participants (p = 0.03/0.03, 6-week node; p = 0.02/0.03 12-week primary tumour) but not in the HPV-OPC subgroup. In participants with DFS, percentage interval changes in primary tumour ADCmean at 6- and 12-weeks were higher in HPV-OPC than other HNSCC (p = 0.01, 6 weeks; p = 0.005, 12 weeks). The 12-week post-CRT SUVmax did not predict DFS. Conclusion Absolute post-CRT ADCmean values predicted DFS in HNSCC but not in the HPV-OPC subgroup. Amongst participants with DFS, post-CRT percentage interval changes in primary tumour ADCmean were significantly higher in HPV-OPC than in other HNSCC. Knowledge of HPV-OPC status is crucial to the clinical utilisation of post-CRT DWI-MRI for the prediction of outcomes. Supplementary Information The online version contains supplementary material available at 10.1007/s00432-021-03662-y.

Background:Sarcoma of the head and neck is a rare condition that poses significant challenges in management and often requires radical multimodality treatment.Objectives:This study aimed to analyse current clinical presentation, evaluation, management dilemmas and oncological outcomes.Methods:Computer records and case notes were analysed, and 39 patients were identified. Variables were compared using Pearson's chi-square test and the log-rank test, while survival outcomes were calculated using the Kaplan–Meier method.Results:The histopathological diagnosis was Kaposi sarcoma in 20.5 per cent of cases, chondrosarcoma in 15.3 per cent and osteosarcoma in 10.2 per cent. A range of other sarcomas were diagnosed in the remaining patients. The site of disease was most commonly sinonasal, followed by the oral cavity and larynx.Conclusion:Wide local excision with clear resection margins is essential to achieve local control and long-term survival. There is a need for cross-specialty collaboration in order to accrue the evidence which will be necessary to improve long-term outcomes.

Purpose: To determine the feasibility of induction chemotherapy and chemo-IMRT in head and neck squamous cell cancers at risk of bilateral nodal spread (midline tumours) and to evaluate whether bilateral superficial lobe parotid-sparing IMRT can reduce the incidence of ⩾G2 subjective xerostomia. Methods: Patients with midline tumours were enrolled to a phase II trial to receive induction platinum/5-fluorouracil and concomitant platinum with combined superficial lobe parotid-sparing IMRT. The primary site and involved nodal levels received 65 Gy in 30 fractions (f) and at risk nodal levels, 54 Gy/30f. Incidence of ⩾G2 subjective xerostomia was defined as the primary endpoint. Secondary endpoints included incidences of acute and late toxicities and survival outcomes dependent on human papilloma virus (HPV) status. Results: One hundred and twenty patients with midline cancers completed treatment between December 2005 and May 2010 with median follow-up of 50 months. Incidences of ⩾G2 acute toxicities were: dysphagia 75% xerostomia 65% mucositis 86% pain 83% and fatigue 64%. At 12 months, ⩾G2 subjective xerostomia was observed in 21% (17% in HPV +ve). Two-year loco-regional progression-free survival (PFS) was 90.7% (95% CI: 85.2–96.2). According to HPV status, there was a significant difference for 2-year loco-regional PFS, 76.8% (HPV-negative) vs 98.6% (HPV-positive), P=0.001. 2-year overall survival was 93% for HPV-positive compared with 52% for HPV-negative cases, P

Background\ud\udBreast, cervical and colorectal cancers are the three most frequent cancers in women, while lung, prostate and colorectal cancers are the most frequent in men. Much attention has been given to the economic evaluation of pharmaceuticals for treatment of cancer by the National Institute for Health and Care Excellence (NICE) in the UK and similar authorities internationally, while economic analysis developed for other types of anti-cancer interventions, including radiotherapy and surgery, are less common.\udObjectives\ud\udOur objective was to review methods used in published cost-effectiveness studies evaluating radiotherapy for breast, cervical, colorectal, head and neck and prostate cancer, and to compare the economic evaluation methods applied with those defined in the guidelines used by the NICE technology appraisal programme.\udMethods\ud\udA systematic search of seven databases (MEDLINE, EMBASE, CDSR, NHSEED, HTA, DARE, EconLit) as well as research registers, the NICE website and conference proceedings was conducted in July 2012. Only economic evaluations of radiotherapy interventions in individuals diagnosed with cancer that included quality-adjusted life-years (QALYs) or life-years (LYs) were included. Included studies were appraised on the basis of satisfying essential, preferred and UK-specific methods requirements, building on the NICE Reference Case for economic evaluations and on other methods guidelines.\udResults\ud\udA total of 29 studies satisfied the inclusion criteria (breast 14, colorectal 2, prostate 10, cervical 0, head and neck 3). Only two studies were conducted in the UK (13 in the USA). Among essential methods criteria, the main issue was that only three (10 %) of the studies used clinical-effectiveness estimates identified through systematic review of the literature. Similarly, only eight (28 %) studies sourced health-related quality-of-life data directly from patients with the condition of interest. Other essential criteria (e.g. clear description of comparators, patient group indication and appropriate time horizon) were generally fulfilled, while most of the UK-specific requirements were not met.\udConclusion\ud\udBased on this review there is a dearth of up-to-date, robust evidence on the cost effectiveness of radiotherapy in cancer suitable to support decision making in the UK. Studies selected did not fully satisfy essential method standards currently recommended by NICE.

OBJECTIVES To analyse survival and toxicity outcomes in patients treated with primary intensity-modulated radiotherapy (IMRT) for oropharyngeal squamous cell carcinoma (OPSCC) in the era of routine human papilloma virus (HPV) testing. DESIGN Single-institution case series. SETTING Tertiary Head and Neck Cancer Unit. PARTICIPANTS A total of 186 patients received IMRT (+/- chemotherapy) for radical primary treatment of OPSCC between March 2010 and December 2013. HPV status was available for 88% of cases. Median radiation dose was 65 Gy in 30 daily fractions. 90% of stage III/IV patients received concurrent chemotherapy or cetuximab. MAIN OUTCOME MEASURES Overall, disease-free and disease-specific survival; rates of late xerostomia and dysphagia. RESULTS A total of 177 patients completed treatment (Stage I/II: 23; Stage III/IV: 154), with median follow-up of 26 months. Estimated 3-year overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS) rates were 77.2% (70.5-83.9), 72.3% (65.4-79.2) and 80.2% (74.1-86.3). Estimated 3-year OS, DFS and DSS for HPV-positive patients were 90.9% (85.2-96.6), 87.9% (81.4-94.4) and 91.8% (86.3-97.3). A previously identified risk stratification method was validated, showing improved OS for low-risk over high-risk patients (HR 0.09, P < 0.001). The 2-year feeding tube retention rate was 6%, and 2-year grade ≥2 xerostomia rate was 38% (23% if mean contralateral parotid dose

A significant number of adult pre- menopausal women are offered pelvic radical radiotherapy as part of the management of their malignancy. Advances in human reproductive research are making pregnancy a possibility for these women, but ovarian function, however, is not the only requirement for establishing and maintaining a pregnancy that will result in the delivery of a normal infant. The processes of implantation, fetal and placental development and labour require normal cervical structure and function. Radiation induces acute and late changes in the uterus that have a permanent impact. This article aims to summarise the published data on this complex subject. To date, the majority of reports of successful pregnancies refer to women who had hemi-pelvis or abdominal irradiation suggesting that partial volume irradiation of the uterus may not preclude pregnancy. However, with the current available information, women receiving a radical dose of radiotherapy to the whole uterus are very unlikely to have a successful pregnancy even if ovarian function is maintained. Systematic studies and, in particular, studies looking at modern radiotherapy techniques are required, as well as a register of pregnancies and outcomes to be able to provide answers for this group of patients.

To evaluate an alternative treatment for advanced or metastatic urothelial cancers, a dose-intensive combination chemotherapy regimen using carboplatin, methotrexate, vincristine and cisplatin was given to 60 patients over a 3-year period (1990 to 1993). There were 26 patients with locally advanced disease and 34 with metastatic disease; 49 patients were evaluable for response. A complete response was noted in four patients (8%) and a partial response in 15 (31%), for an overall response rate of 39%. The median survival was 12 months. Two- and 5-year survival rates were 25.5% (95% confidence interval CI) 15.2-37.0) and 7.3% (95% CI 2.2-16.4) respectively. Failure-free survival was 15.3% (95% CI 7.5-25.6) at 2 years and 5.9% (95% CI 1.6-14.4) at 5 years, with a median of 8 months. For the responders, the median duration of response was 14 months, with a range of 2-59+ months. Toxicity included myelosuppression (28% grade 4/5 neutropenia, 19% grade 4 thrombocytopenia), peripheral neuropathy (54% grade 1 and 23% grade 2/3) and ototoxicity (21% grade 1, 19% grade 2). This schedule of dose-intensified platinum-based chemotherapy for bladder cancer resulted in significant neurotoxicity without evidence of enhanced response rates or survival. Regimens such as methotrexate, vinblastine, doxorubicin and cisplatin should remain standard. Accelerated regimens may be useful in situations were it is necessary to administer chemotherapy over a short time (e.g. as part of combined modality treatment).

Objective: To investigate the effect of 6 and 15&emsp14;MV photon energies on intensity-modulated radiation therapy (IMRT) prostate cancer treatment plan outcome and to compare the theoretical risks of secondary induced malignancies. Methods: Separate prostate cancer IMRT plans were prepared for 6 and 15&emsp14;MV beams. Organ equivalent doses were obtained through thermoluminescent dosimeter (TLD) measurements in a Rando phantom. The neutron dose contribution at 15&emsp14;MV was measured using polyallyl-diglycol-carbonate (PADC) neutron track etch detectors. Risk coefficients from ICRP Report 103 were used to compare the risk of fatal secondary induced malignancies in out-of-field organs and tissues for 6 and 15&emsp14;MV. For the bladder and the rectum, a comparative evaluation of the risk using three separate models was carried out. Dose-volume parameters for the rectum, bladder and prostate planning-target-volume were evaluated, as well as normal tissue complication probability (NTCP) and tumour control probability (TCP) calculations. Results: There is a small increased theoretical risk of developing a fatal cancer from 6&emsp14;MV compared with 15&emsp14;MV, taking into account all the organs. Dose-volume parameters for the rectum and bladder show that 15&emsp14;MV results in better volume sparing in the regions below 70&emsp14;Gy, but the volume exposed increases slightly beyond this in comparison to 6&emsp14;MV, resulting in a higher NTCP for the rectum of 3.6% versus 3.0% (p = 0.166). Conclusion: The choice to treat using IMRT at 15&emsp14;MV should not be excluded, but should be based on risk versus benefit, considering the age and life expectancy of the patient together with the relative risk of radiation-induced cancer and NTCPs.

AIM: Pelvic irradiation in addition to prostate irradiation may improve outcome in locally advanced prostate cancer, but is associated with dose-limiting bowel toxicity. We report the preliminary results of a dose escalation study using intensity-modulated radiotherapy. MATERIALS AND METHODS: Eligible patients had high-risk (T3, Gleason > or =8 or prostate-specific antigen > or =20 ng/ml) or lymph node-positive disease. Intensity-modulated radiotherapy was inverse planned giving 70 Gy/35 fractions to the prostate and 50 Gy/55 Gy/60 Gy in sequential cohorts to the pelvis with a 5 Gy boost to positive lymph nodes. Acute and late toxicity were recorded with Radiation Therapy Oncology Group (RTOG) and Late Effects Normal Tissue - Subjective Objective Management LENT-SOM scales. Neoadjuvant androgen suppression was given for 3 years. This report concerns the 50 and 55 Gy cohorts. RESULTS: Seventy-nine men were recruited (25 to 50 Gy/54 to 55 Gy) with a median follow-up of 2 years. Patients were divided into two groups according to the total bowel volume outlined (median 450 cm(3)). Acute RTOG (> or =2) bowel toxicity was 40 and 50% for the 50 and 55 Gy groups and 38 and 51% for bowel volume or =450 cm(3), respectively, suggesting both volume and dose relationships for acute effects. Late RTOG diarrhoea > or =grade 2 was only seen with bowel volume > or =450 cm(3), but no dose effect was apparent (12%/50 Gy and 10%/55 Gy). LENT-SOM bowel > or =grade 2 toxicity occurred in 22%/50 Gy and 15%/55 Gy. Only one patient had grade 3 toxicity. A dose volume histogram analysis showed increased late RTOG diarrhoea > or =grade 2 with larger bowel volume irradiated, significant for BV40 >124 cm(3) (P=0.04), BV45 >71 cm(3) (P=0.03) and BV60 >2 cm(3) (P=0.01). CONCLUSIONS: Acute and late bowel toxicity was acceptably low using a pelvic dose of up to 55 Gy over 7 weeks. Both relate to total pelvic bowel volume and dose volume constraints have been defined.

The purpose of this study was to compare conventional radiotherapy with parotid gland-sparing intensity-modulated radiation therapy (IMRT) using the PARSPORT trial. The validity of such a trial depends on the radiotherapy planning and delivery meeting a defined standard across all centres. At the outset, many of the centres had little or no experience of delivering IMRT; therefore, quality assurance processes were devised to ensure consistency and standardisation of all processes for comparison within the trial. The pre-trial quality assurance (QA) programme and results are described. Each centre undertook exercises in target volume definition and treatment planning, completed a resource questionnaire and produced a process document. Additionally, the QA team visited each participating centre. Each exercise had to be accepted before patients could be recruited into the trial. 10 centres successfully completed the quality assurance exercises. A range of treatment planning systems, linear accelerators and delivery methods were used for the planning exercises, and all the plans created reached the standard required for participation in this multicentre trial. All 10 participating centres achieved implementation of a comprehensive and robust IMRT programme for treatment of head and neck cancer.

Intensity-modulated radiotherapy (IMRT) is a novel conformal radiotherapy technique which is gaining increasing clinical use worldwide. This article aims to summarize the published data pertaining to clinical indications of this therapy for head and neck, central nervous system, and lung tumours. The main indications in head and neck cancer are parotid gland sparing and dose escalation to tumours close to organs at risk. For central nervous system tumours, IMRT has been used to reduce normal tissue radiation by more conformal dose distributions. To date, the majority of reports concern patients treated in the context of clinical trials, and for most tumour types longer term follow up of treated patients will be required to confirm the clinical benefits of IMRT.