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Background: The optimal hypofractionated schedule of post-prostatectomy radiotherapy remains to be established. We evaluated treatment outcomes and toxicity of moderately hypofractionated post-prostatectomy radiotherapy in 16 daily fractions delivered with intensity-modulated radiotherapy. The treatment schedule selection was motivated by limited technology resources and was radiobiologically dose-escalated. Methods: One hundred consecutive M0 patients with post-prostatectomy radiotherapy were evaluated. Radiotherapy indication was adjuvant (ART) in 19%, early-salvage (eSRT) in 46% and salvage (SRT) in 35%. The dose prescription for prostate bed planning target volume was 52.8 Gy in 16 fractions of 3.3 Gy. The Common Terminology Criteria v. 4 for Adverse Events scale was used for toxicity grading. Results: The median follow-up was 61 months. Five-year biochemical recurrence-free survival (bRFS) was 78.6%, distant metastases-free survival (DMFS) was 95.7% and overall survival was 98.8%. Treatment indication (ART or eSRT vs. SRT) was the only significant factor for bRFS (HR 0.15, 95% CI 0.05–0.47, p = 0.001) and DMFS (HR 0.16, 95% CI 0.03–0.90; p = 0.038). Acute gastrointestinal (GI) toxicity grade 2 was recorded in 24%, grade 3 in 2%, acute genitourinary (GU) toxicity grade 2 in 10% of patients, and no grade 3. A cumulative rate of late GI toxicity grade ≥ 2 was observed in 9% and late GU toxicity grade ≥ 2 in 16% of patients. Conclusions: The observed results confirmed efficacy and showed a higher than anticipated rate of early GI, late GI, and GU toxicity of post-prostatectomy radiobiologically dose-escalated hypofractionated radiotherapy in 16 daily fractions. [ABSTRACT FROM AUTHOR]

Simple Summary: Current options for the curative treatment of the non-metastatic oropharyngeal carcinoma associated with human papillomavirus include minimally-invasive surgery or radiotherapy, which is combined with chemotherapy in many clinical situations. The aim of this review is to summarize the current treatment recommendations in the local therapy of human papillomavirus-associated oropharyngeal cancer, with respect to the latest published evidence in the field. Future perspectives and next-generation research pathways, including treatment deintensification methods, are thoroughly discussed. Over the last two decades, human papillomavirus (HPV) has caused a new pandemic of cancer in many urban areas across the world. The new entity, HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), has been at the center of scientific attention ever since, not only due to its distinct biological behavior, but also because of its significantly better prognosis than observed in its HPV-negative counterpart. The very good treatment outcomes of the disease after primary therapy (minimally-invasive surgery, radiation therapy with or without chemotherapy) resulted in the creation of a separate staging system, reflecting this excellent prognosis. A substantial proportion of newly diagnosed HPV-driven OPSCC is diagnosed in stage I or II, where long-term survival is observed worldwide. Deintensification of the primary therapeutic methods, aiming at a reduction of long-term toxicity in survivors, has emerged, and the quality of life of the patient after treatment has become a key-point in many clinical trials. Current treatment recommendations for the treatment of HPV-driven OPSCC do not differ significantly from HPV-negative OPSCC; however, the results of randomized trials are eagerly awaited and deemed necessary, in order to include deintensification into standard clinical practice. [ABSTRACT FROM AUTHOR]

Meta-analyses of chemotherapy in Head and Neck Cancer (MAC-HNC) showed that adding chemotherapy (CHT) to locoregional treatment improves the treatment outcome. However, it was observed only with concurrent administration of radiotherapy (RT) and CHT. Among many drugs used in this setting, cisplatin (CDDP) has most consistently been used as a single-agent with radical RT. The two most common administrations of CDDP included 100 mg/sqm every three weeks and 40 mg/sqm weekly, both during the course of RT. While a direct comparison of the two modes of CDDP administration in the definitive treatment of locally advanced squamous cell (SQC) HNC is basically lacking, recent summary brought somewhat conflicting results. Questions largely unexplored is the total CDDP dose deemed necessary when administered concurrently with radical RT. Subset analyses from various prospective randomized trials and meta-analyses seem to indicate that one may not need a total CDDP dose of significantly higher than 200 mg/sqm if at all higher than that, irrespective of the type of RT administered and seemingly unnecessary in HPV+ oropharyngeal cancer patients. Due to presumably lower but still effective threshold level of total CDDP given with RT may depend on other factors, such as frequency of CDDP administration or RT fractionation pattern and be closely interrelated with anticipated toxicity, researchers continue with their quest to find optimal approach in this setting. Large clinical trials should detect small differences between treatment options in an era when "old" but effective drugs still dominate the research arena of SQC HNC. [ABSTRACT FROM AUTHOR]

Here we present a summary of existing evidence from meta-analyses and systematic reviews in the setting of locally advanced, inoperable squamous cell cancer of the head and neck, treated with radical radiotherapy and concurrent cisplatin therapy either weekly or every 3 weeks. Taken together, the data seem to indicate that there is no difference in major outcomes, including toxicity. However, caution in the interpretation of the data should be exercised due to poor quality of original studies, none of which was a prospective randomized phase III trial. Practicing clinicians should continue using their best judgment about the most appropriate treatment option in this setting, taking into account both the existing evidence and also various patient and tumor characteristics. [ABSTRACT FROM AUTHOR]

Squamous cell head and neck cancer (SCHNC) is the seventh most common cancer worldwide. Most of SCHNC are locally advanced at diagnosis and are treated with combination of surgery and/or radiotherapy with chemotherapy. In spite of aggressive treatment, many patients relapse within the 3 years following the diagnosis. Those whose tumor cannot be resected or reirradiated are treated with a systemic treatment mostly in a palliative setting. They are identified as recurrent and/or metastatic SCHNC (R/MSCHNC) patients. First-line treatment of R/M-SCHNC historically consisted of cytotoxic agents such as methotrexate, bleomycin, or platinum-based protocols until targeted biological therapies were introduced in the 2000's. The recent years witnessed a shift in systemic treatment toward the use of monoclonal antibodies and tyrosine kinase inhibitors, largely based on recent understanding of the role of immune dysfunction in SCHNC. Our review focuses on recent developments of molecular-targeted and immunotherapies in the treatment SCHNC, mostly focusing on R/M-SCHNC. It also highlights ongoing trials and discusses some promising novel targets in HNC, as well as clinical trial design challenges. [ABSTRACT FROM AUTHOR]

The last three decades provided new insights into the discovery of the entity related to several strains of human papillomavirus (HPV). The viral cause of HPV, primarily found in the oropharynx, was officially recognized by the World Health Organization in 2007. While epidemiologic studies around the world showed an increased incidence of HPV-related heads and neck cancers (HNC), they also established a photo robot of a typical person suffering from HPV: younger white man, suffering from a nonkeratinized type of squamous cell carcinoma, rarely being seen as heavy smoker and/or drinker. The patient with specific sexual behavior pattern usually carried low T and high N burden, HPV16 being detected in the vast majority of HPV+ tumors, mostly in the oropharynx. It was also recognized that HPV-related cancers seem to have a better prognosis than their HPV-unrelated counterparts. This observation served as an important starting point for clinical studies aiming first to identify different risk groups and then to design various de-intensification treatment strategies which aimed to maintain high success rate with e.g. lower radiotherapy and/or chemotherapy doses while decreasing side effects such deintensified treatment strategies should bring. This review summarizes the most important aspects of HPV-related HNC. [ABSTRACT FROM AUTHOR]

Radiation therapy (RT) is an important treatment modality in head and neck cancer (HNC) irrespective of stage, histology, and location of the primary tumor in both curative and palliative setting, with or without other treatment modalities such as surgery or chemotherapy. Based on advances with better imaging and introduction of sophisticated software for treatment and planning systems, radiation oncology of HNC witnessed major advantages resulting in both improved local control and better sparing of organs at risk. From computed tomography to magnetic resonance imaging and introduction of positron emission tomography with various radiotracers it became possible not only to diagnose and stage HNC with more confidence but also to introduce these technologies in RT treatment planning, and to use it during the RT course for the evaluation of response and additionally sculpture RT fields. Furthermore, it became possible to predict outcome based on anatomic and metabolic changes in HNC. Community of radiation oncologists successfully adopted transition from two-dimensional to three-dimensional RT and then to intensity modulated RT, as well as stereotactic radiotherapy (either single- or multi-fraction) regimens. There is renewed interest in heavy particles with both neutrons, carbon-ions and protons, the latter two being used more frequently in the recent years. This review article summarizes the most important accepts of novel RT technologies in HNC. [ABSTRACT FROM AUTHOR]

Simple Summary: Options for the curative treatment of locally recurrent nasopharyngeal carcinoma include surgery or re-irradiation. Both approaches have been scientifically explored, yet there is no consensus on the indication or definitive preference of the above two salvage treatments. The aim of this review is to summarize the current evidence on the local treatment of recurrent nasopharyngeal carcinoma. The feasibility, safety, and efficacy of salvage surgery and radical re-irradiation are discussed. Recommendations on treatment modifications during the coronavirus disease 2019 pandemic are included as well. Recurrent nasopharyngeal carcinoma represents an extremely challenging therapeutic situation. Given the vulnerability of the already pretreated neurological structures surrounding the nasopharynx, any potential salvage retreatment option bears a significant risk of severe complications that result in high treatment-related morbidity, quality of life deterioration, and even mortality. Yet, with careful patient selection, long-term survival may be achieved after local retreatment in a subgroup of patients with local or regional relapse of nasopharyngeal cancer. Early detection of the recurrence represents the key to therapeutic success, and in the case of early stage disease, several curative treatment options can be offered to the patient, albeit with minimal support in prospective clinical data. In this article, an up-to-date review of published evidence on modern surgical and radiation therapy treatment options is summarized, including currently recommended treatment modifications of both therapeutic approaches during the coronavirus disease 2019 pandemic. [ABSTRACT FROM AUTHOR]

Although conventional fractionated (CF) radiotherapy (RT) became the most common non-surgical approach delivering 66-70 Gy in 33-35 daily fractions (fx) in 6.5-7 weeks several decades ago due to a good local control (LC) with low normal tissue complication rates, recent decades also brought altered fractionated RT regimens based on better understanding of radiobiology. Of these, split course RT is largely abandoned due to inferior results caused by the treatment gap, which led to inferior local control rates and consequently survival. Hyperfractionated (Hfx) RT and various forms of accelerated (Acc) RT had consistently shown improvement in the treatment outcome, given either alone or with concurrent chemotherapy (CHT). Hfx RT was most consistently superior to CF and frequently to Acc RT, while moderate Acc RT also holds promise to be used more often in daily clinical practice. The use of Hfx RT may face the challenge of applicability in busy radiotherapy departments around the world despite unequivocally having been proven as superior regarding both local/regional tumor control and overall survival. With concurrent CHT, although results favor it, risks of accompanying toxicity rise and should be considered when planning such intensified treatment approach. [ABSTRACT FROM AUTHOR]

Background: Alveolar echinococcosis (AE) is a severe helminth disease affecting humans, which is caused by the fox tapeworm Echinococcus multilocularis. AE represents a serious public health issue in larger regions of China, Siberia, and other regions in Asia. In Europe, a significant increase in prevalence since the 1990s is not only affecting the historically documented endemic area north of the Alps but more recently also neighbouring regions previously not known to be endemic. The genetic diversity of the parasite population and respective distribution in Europe have now been investigated in view of generating a fine-tuned map of parasite variants occurring in Europe. This approach may serve as a model to study the parasite at a worldwide level. Methodology/Principal Findings: The genetic diversity of E. multilocularis was assessed based upon the tandemly repeated microsatellite marker EmsB in association with matching fox host geographical positions. Our study demonstrated a higher genetic diversity in the endemic areas north of the Alps when compared to other areas. Conclusions/Significance: The study of the spatial distribution of E. multilocularis in Europe, based on 32 genetic clusters, suggests that Europe can be considered as a unique global focus of E. multilocularis, which can be schematically drawn as a central core located in Switzerland and Jura Swabe flanked by neighbouring regions where the parasite exhibits a lower genetic diversity. The transmission of the parasite into peripheral regions is governed by a "mainland–island" system. Moreover, the presence of similar genetic profiles in both zones indicated a founder event. Author Summary: Echinococcus multilocularis is a tapeworm of the red fox, which represents a considerable health threat to respectively infected humans. Main endemic areas are located in China, Siberia, and central Europe. Alarmed by an emerging or reemerging situation in Europe, the question of how the parasite gets spatially and temporally spread and transmitted becomes essential to prepare appropriate control programs. The question was tackled by using genetic data on a large sample size of E. multilocularis adult stage tapeworms, combined with geographical site location data input. The historically documented endemic area, represented by the northern Alpine arch, was shown to harbour the highest genetic richness and diversity, as compared to surrounding areas in northern and eastern Europe. The spatial and temporal spread of different E. multilocularis genotypes in Europe seems to be ruled by a founder event, linked to exportation of parasites from the central core to newly identified (western and eastern) areas or subregions, where these parasites could subsequently disseminate under geographical separation from the original foci. [ABSTRACT FROM AUTHOR]

Background: Alveolar echinococcosis (AE) is a severe helminth disease affecting humans, which is caused by the fox tapeworm Echinococcus multilocularis. AE represents a serious public health issue in larger regions of China, Siberia, and other regions in Asia. In Europe, a significant increase in prevalence since the 1990s is not only affecting the historically documented endemic area north of the Alps but more recently also neighbouring regions previously not known to be endemic. The genetic diversity of the parasite population and respective distribution in Europe have now been investigated in view of generating a fine-tuned map of parasite variants occurring in Europe. This approach may serve as a model to study the parasite at a worldwide level. Methodology/Principal Findings: The genetic diversity of E. multilocularis was assessed based upon the tandemly repeated microsatellite marker EmsB in association with matching fox host geographical positions. Our study demonstrated a higher genetic diversity in the endemic areas north of the Alps when compared to other areas. Conclusions/Significance: The study of the spatial distribution of E. multilocularis in Europe, based on 32 genetic clusters, suggests that Europe can be considered as a unique global focus of E. multilocularis, which can be schematically drawn as a central core located in Switzerland and Jura Swabe flanked by neighbouring regions where the parasite exhibits a lower genetic diversity. The transmission of the parasite into peripheral regions is governed by a ''mainland-island'' system. Moreover, the presence of similar genetic profiles in both zones indicated a founder event. [ABSTRACT FROM AUTHOR]