Incidence and Survival for Head and Neck Cancers in Estonia, 1996-2016: A Population-Based Study.

BACKGROUND: Changing patterns of alcohol and tobacco consumption and human papillomavirus (HPV) infection have affected the epidemiology of head and neck cancers. The aim of this study was to examine 20-year trends in the incidence and survival of head and neck cancers in Estonia by site, sex, morphology, and stage. METHODS: Data on all adult cases of invasive head and neck cancers diagnosed in Estonia in 1996-2016 were obtained from a population-based cancer registry. TNM stage was available for 2010-2016. Incidence trends were modeled with join-point regression, and five-year relative survival ratios (RSRs) were calculated. RESULTS: A total of 6,769 cases were included, 64% men. We observed declining incidence of lip and laryngeal cancer and substantial increases in the incidence of hypopharyngeal and oropharyngeal cancers. Over 60% of mouth and pharyngeal cancers were diagnosed at stage IV. Age-standardized 5-year RSR for mouth and pharyngeal cancer increased substantially over the study period, from 21% (95% CI 16%-25%) in 1996-2002 to 33% (29%-38%) in 2010-2016. The largest survival increases were seen for cancers of the oral cavity (reaching 44% in 2010-2016), tongue (41%), and larynx (63%), while modest changes were seen for the oropharynx (24%) and hypopharynx (17%). The latest 5-year RSR was 90% for thyroid cancers (99% for papillary carcinoma). Large female survival advantage was seen for most sites. CONCLUSION: The observed trends suggest an emerging role of HPV infection in combination with traditional risk factors in the development of head and neck cancers in Estonia. Efforts targeting health behavior, HPV vaccination, and earlier diagnosis are crucial for reducing mortality from these cancers.

A Nordic-Baltic perspective on indications for proton therapy with strategies for identification of proper patients.

The beneficial effects of protons are primarily based on reduction of low to intermediate radiation dose bath to normal tissue surrounding the radiotherapy target volume. Despite promise for reduced long-term toxicity, the percentage of cancer patients treated with proton therapy remains low. This is probably caused by technical improvements in planning and delivery of photon therapy, and by high cost, low availability and lack of high-level evidence on proton therapy. A number of proton treatment facilities are under construction or have recently opened; there are now two operational Scandinavian proton centres and two more are under construction, thereby eliminating the availability hurdle. Even with the advantageous physical properties of protons, there is still substantial ambiguity and no established criteria related to which patients should receive proton therapy. This topic was discussed in a session at the Nordic Collaborative Workshop on Particle Therapy, held in Uppsala 14-15 November 2019. This paper resumes the Nordic-Baltic perspective on proton therapy indications and discusses strategies to identify patients for proton therapy. As for indications, neoplastic entities, target volume localisation, size, internal motion, age, second cancer predisposition, dose escalation and treatment plan comparison based on the as low as reasonably achievable (ALARA) principle or normal tissue complication probability (NTCP) models were discussed. Importantly, the patient selection process should be integrated into the radiotherapy community and emphasis on collaboration across medical specialties, involvement of key decision makers and knowledge dissemination in general are important factors. An active Nordic-Baltic proton therapy organisation would also serve this purpose.

IAEA-HypoX. A randomized multicenter study of the hypoxic radiosensitizer nimorazole concomitant with accelerated radiotherapy in head and neck squamous cell carcinoma.

PURPOSE: To test the hypothesis that radiotherapy (RT) of head and neck squamous cell carcinoma (HNSCC) can be improved by hypoxic modification using nimorazole (NIM) in association with accelerated fractionation. MATERIALS AND METHODS: The protocol was activated in March 2012 as an international multicenter randomized trial in patients with HNSCC. Tumors were treated to a dose of 66-70Gy, 33-35 fractions, 6 fractions per week. NIM was administered in a dose of 1.2gperm(2), 90min before the first daily RT fraction. The primary endpoint was loco-regional failure. The trial was closed prematurely by June 2014 due to poor recruitment. An associated quality assurance program was performed to ensure the consistency of RT with the protocol guidelines. RESULTS: The trial was dimensioned to include 600 patients in 3years, but only 104 patients were randomized between March 2012 and May 2014 due to the inability to involve three major centers and the insufficient recruitment rate from the other participating centers. Twenty patients from two centers had to be excluded from the analysis due to the unavailability of the follow-up data. Among the remaining 84 patients, 82 patients were evaluable (39 and 43 patients in the RT+NIM and the RT-alone arms, respectively). The treatment compliance was good with only six patients not completing the full planned RT course, and 31 patients (79%) out of 39 allocated for NIM, achieving at least 90% of the prescribed drug dose. At the time of evaluation, 40 patients had failed to achieve persistent loco-regional tumor control, and a total of 45 patients had died. The use of NIM improved the loco-regional tumor control with an 18month post-randomization cumulative failure rate of 33% versus 51% in the control arm, yielding a risk difference of 18% (CI -3% to 39%; P=0.10). The corresponding values for overall death was 43% versus 62%, yielding a risk difference of 19% (CI -3% to 42%; P=0.10). Sixteen patients, out of 55 patients analyzed for hypoxic gene expression, were classified as having more hypoxic tumors. Such patients, if treated with RT alone, had a higher loco-regional tumor failure rate as compared to the rest of the patients with known hypoxic status (P=0.05). CONCLUSION: Although the trial was incomplete and suffered from a small number of patients, the results suggested an improvement in loco-regional tumor control and overall survival in patients with advanced HNSCC given the hypoxic modifier NIM in addition to accelerated fractionation RT. However, the trial also revealed that conducting multicenter and multinational study combining drug and RT in developing countries may suffer from uncontrolled and unsolvable problems.

Five versus six fractions of radiotherapy per week for squamous-cell carcinoma of the head and neck (IAEA-ACC study): a randomised, multicentre trial.

BACKGROUND: Several large randomised studies from western Europe and the USA have shown that accelerated fractionation of radiotherapy might be beneficial in the treatment of squamous-cell carcinoma of the head and neck (HNSCC). The aim of this study--the International Atomic Energy Agency (IAEA) ACC trial--was to determine whether accelerated fractionation could be applied in developing countries, where there are fewer therapeutic resources and where tumour burdens can be heavier. METHODS: Between Jan 6, 1999, to March 31, 2004, nine centres from Asia, Europe, the Middle East, Africa, and South America recruited patients with HNSCC of the larynx, pharynx, and oral cavity who were eligible for curative radiotherapy. Patients were randomly assigned in this open-label trial to receive an accelerated regimen of six fractions of radiotherapy per week (n=458) or to receive a conventional radiotherapy regimen of five fractions per week (n=450), receiving a total dose of 66-70 Gy in 33-35 fractions. Patients were stratified by tumour localisation, T classification, histopathological grade, and institution. Randomisation was done by a central computer-generated balanced randomisation algorithm. The primary endpoint was locoregional control, analysed for all eligible patients, irrespective of whether or not they had completed the course of radiotherapy. This trial is registered with ClinicalTrials.gov, number NCT00120211. FINDINGS: Six patients in the accelerated group and two in the conventional group were excluded from analyses because of withdrawal of consent or missing data. The planned total radiotherapy dose was received by 418 (92%) of the 452 eligible patients in the accelerated radiotherapy group and 413 (92%) of the 448 patients in the conventional radiotherapy group. Median treatment time was 40 days in the accelerated group and 47 days in the conventional group. The 5-year actuarial rate of locoregional control was 42% in the accelerated group versus 30% in the conventional group (hazard ratio [HR] 0.63, 95% CI 0.49-0.83; p=0.004). Acute morbidity in the form of confluent mucositis was noted in 45 patients in the accelerated group and 22 patients in the conventional group (2.15, 1.27-3.35); severe skin reactions were noted in 87 patients in the accelerated group and 50 patients in the conventional group (1.91, 1.31-2.79). There were no significant differences in late radiation side-effects. INTERPRETATION: An accelerated schedule of radiotherapy for HNSCC was more effective than conventional fractionation, and since it does not require additional resources, might be a suitable new worldwide standard baseline treatment for radiotherapy of HNSCC. FUNDING: International Atomic Energy Agency, Coordinated Research Project (IAEA-CRP E.3.30.18), the Danish Cancer Society, the Danish Strategic Research Council, and the Lundbeck Centre for Interventional Research in Radiation Oncology (CIRRO).

Resources and management strategies for the use of radiotherapy in the treatment of lung cancer in Central and Eastern European countries: results of an International Atomic Energy Agency (IAEA) survey.

PURPOSE: To assess resources and management strategies for the use of radiotherapy (RT) in the treatment of lung cancer in developing Central and Eastern European countries. MATERIALS/METHODS: Questionnaires on patterns of care of NSCLC and SCLC were sent to radiation oncologists of Central and Eastern Europe. Comparisons were made between two groups of countries-ex-USSR states and other Eastern and Central European countries. RESULTS: Twenty-four out of twenty-eight surveyed countries responded. There were significant differences in access to modern treatment facilities (3D planning systems, number of linear accelerators), percentage of patients with lung cancer receiving radiotherapy, schedules of palliative RT, use of postoperative RT for early stages between both analysed groups of countries. 3D systems were in use in 25% of centres for an entire treatment, in 28% for a part of the treatment, and in 47% curative RT was 2D planned. Sequential chemo-RT was the most common approach to radical management of NSCLC, followed by RT alone and concomitant chemo-RT; median percentages of patients receiving respective treatments per centre were 57%, 30%, and 10%. For SCLC, the concurrent approach was declared by 56%, and the sequential approach by 42% of responders. CONCLUSIONS: Patterns of care of lung cancer in the analysed countries differed in some part from existing, evidence-based data on lung cancer. In particular, this difference was observed between ex-USSR countries and the rest of European developing countries in the equipment available and specific diagnostic and treatment parameters in radiotherapy of lung cancer, the latter group's practices more resembling those of developed European countries.