Importance:Treating locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) involves any combination of surgery, radiation, and chemotherapy, followed by routine monitoring for local recurrence or distant metastases. Given the poor patient outcomes, a significant unmet clinical need for improved treatment options remains. Objective:To evaluate efficacy and safety of maintenance atezolizumab in patients with LA SCCHN at high risk of disease progression after multimodal definitive treatment. Design, Setting, and Participants:IMvoke010 was a phase 3, global, double-blind, randomized clinical trial. Patients were recruited at 128 sites in 23 countries between April 3, 2018, and February 14, 2020 (clinical cutoff date: September 27, 2023). Eligible patients had LA SCCHN (stage IVa/IVb involving the oral cavity, larynx, hypopharynx, or human papillomavirus-negative oropharynx, or stage III human papillomavirus-positive oropharynx [AJCC Cancer Staging Manual, eighth edition]) without disease progression after multimodal definitive treatment. Intervention:Patients were randomized (1:1) to receive atezolizumab 1200 mg or placebo every 3 weeks for 1 year or until disease recurrence, disease progression, unacceptable toxicity, or consent withdrawal. Main Outcomes and Measures:The primary end point was investigator-assessed event-free survival. Other end points included overall survival and safety. Results:Overall, 406 patients were randomized to receive atezolizumab (n = 203) or placebo (n = 203); baseline demographics were balanced between both treatment groups (<65 years, 142 [70.0%] vs 155 [76.4%]; male, 168 [82.8%] vs 174 [85.7%]; Asian, 68 [35.6%] vs 61 [31.0%]; Black, 1 [0.5%] vs 1 [0.5%]; and White, 121 [63.4%] vs 135 [68.5%], respectively). At clinical cutoff (median follow-up, 46.5 months), median investigator-assessed event-free survival was 59.5 months (95% CI, 46.8 to not estimable) with atezolizumab vs 52.7 months (95% CI, 41.4 to not estimable) with placebo (hazard ratio, 0.94; 95% CI, 0.70-1.26; P = .68). There was no difference in overall survival between atezolizumab and placebo (24-month overall survival, 82.0% vs 79.2%, respectively). No new or unexpected safety signals were identified. Conclusions and Relevance:In this study, atezolizumab did not improve clinical outcomes in patients with LA SCCHN at high risk of disease progression after multimodal definitive treatment. These data contribute to evidence on the limited activity of checkpoint inhibitors in the global population of this disease setting. Overall, the role of immunotherapy for patients with LA SCCHN remains to be determined. Trial Registration:ClinicalTrials.gov Identifier: NCT03452137.

Introduction. Radiotherapy and radiochemotherapy are, besides surgery, common treatments for head and neck cancers. Despite using advanced modern radiation techniques, the late side effects are a serious problem. From a multitude of cytokines and growth factors shown to contribute to the injury process after cancer therapy, transforming growth factor β1 (TGF-β1) is among the most fundamental ones. The study evaluated if a high level of TGF-β1 before, during, and after treatment can predict thyroid gland fibrosis, which causes hypothyroidism, one of the common late side effects of head and neck cancer irradiation. Material and methods. Fifty-six patients with head and neck cancer who underwent radiation alone or concomitant chemoradiotherapy were included in the study. Analyzed variables included thyroid stimulating hormone (TSH), volume and echogenicity of the thyroid gland, and the level of TGF-β1. Results. In comparison to the initial level, statistically significant increased levels of TSH and statistically significant decreased volume of the thyroid gland were observed 6 and 12 months after irradiation. Moreover, statistically significant decreased levels of TGF-β1 were observed one month after irradiation. High levels of TGF-β1 before treatment or changes in TGF-β1 levels during and after treatment influenced changes neither in TSH levels nor in volume and echogenicity of the thyroid gland one year after radiotherapy. Conclusions. Early evaluation of TSH after radiation is needed to predict hypothyroidism. High TGF-β1 levels before and changes during and after radiation cannot predict hypothyroidism one year after treatment.

Introduction. Radiotherapy and radiochemotherapy are, besides surgery, common treatments for head and neck cancers. Despite using advanced modern radiation techniques, the late side effects are a serious problem. From a multitude of cytokines and growth factors shown to contribute to the injury process after cancer therapy, transforming growth factor f31 (TGF-f31) is among the most fundamental ones. The study evaluated if a high level of TGF-f31 before, during, and after treatment can predict thyroid gland fibrosis, which causes hypothyroidism, one of the common late side effects of head and neck cancer irradiation. Material and methods. Fifty-six patients with head and neck cancer who underwent radiation alone or concomitant chemoradiotherapy were included in the study. Analyzed variables included thyroid stimulating hormone (TSH), volume and echogenicity of the thyroid gland, and the level of TGF-f31. Results. In comparison to the initial level, statistically significant increased levels of TSH and statistically significant decreased volume of the thyroid gland were observed 6 and 12 months after irradiation. Moreover, statistically significant decreased levels of TGF-f31 were observed one month after irradiation. High levels of TGF-f31 before treatment or changes in TGF-f31 levels during and after treatment influenced changes neither in TSH levels nor in volume and echogenicity of the thyroid gland one year after radiotherapy. Conclusions. Early evaluation of TSH after radiation is needed to predict hypothyroidism. High TGF-f31 levels before and changes during and after radiation cannot predict hypothyroidism one year after treatment.

Abstract Background: Treatment (tx) for LA SCCHN includes a combination of surgery, radiation and/or chemotherapy followed by monitoring for local recurrence/distant metastases as standard of care. Given poor outcomes, there remains a clear unmet need in this pt population. IMvoke010 (NCT03452137) evaluated the efficacy and safety of atezo in pts with LA SCCHN who are at high-risk for disease progression following multi-modal definitive tx. Methods: Eligible pts with LA SCCHN (Stage IVa or IVb involving the oral cavity, larynx, hypopharynx, HPV negative oropharynx or Stage III HPV positive oropharynx [per AJCC 8th edition]) with no disease progression after multi-modal definitive tx were randomized (1:1) to receive atezo 1200 mg or placebo. Tx was given every 3 weeks for 1 year or until disease progression, unacceptable toxicity or consent withdrawal. Primary endpoint: investigator-assessed event-free survival (INV-EFS). Other key endpoints: overall survival (OS, secondary for efficacy) and safety. Results: A total of 406 pts were randomized to receive either atezo (n=203) or placebo (n=203). 156 (38.4%) pts underwent surgery as part of definitive tx. At clinical cutoff (27 September 2023), median follow-up was 46.5 months (mos). Median INV-EFS was 59.5 mos with atezo vs 52.7 mos with placebo (HR, 0.94; 95% CI, 0.70-1.26). INV-EFS results were generally consistent across all subgroups. OS showed no difference between arms for atezo vs placebo. Safety data are reported (Table). Conclusion: This study did not meet the primary endpoint of INV-EFS, a numerical improvement in INV-EFS was observed for atezo in pts with LA SCCHN, but this was not statistically significant. Atezo was generally well tolerated, and no new safety signals were identified. Table: Key efficacy and safety results Efficacy Atezo (n=203)* Placebo (n=203) Median INV-EFS, mos 59.5 52.7 HR (95% CI) 0.94 (0.70-1.26) P-value 0.6804† Median OS, mos NE NE HR (95% CI) 0.96 (0.68-1.36) Safety, n (%) Grade 3-4 AEs 55 (27.2) 43 (21.2) TRAEs Grade 3-4 20 (9.9) 12 (5.9) Grade 5 AEs 3 (1.5) 5 (2.5) SAEs 32 (15.8) 32 (15.8) AEs leading to tx discontinuation 18 (8.9) 9 (4.4) CI, confidence interval; HR, hazard ratio; *safety-evaluable pts (n=202); †α boundary: 0.0427 Citation Format: Deborah J. Wong, Jérôme Fayette, Maria Teixeira, Kumar Prabhash, Ricard Mesia, Andrzej Kawecki, Arunee Dechaphunkul, José Dinis, Ye Guo, Muneyuki Masuda, Ching-Yun Hsieh, Maria Grazia Ghi, Claudia Vaz de Melo Sette, Tao Jiang, Yibing Yan, Monika Kaul, Ritika Jagtiani, Christina Matheny, Vaikunth Cuchelkar, Robert Haddad. IMvoke010: A phase III, double-blind randomized trial of atezolizumab (atezo) after definitive local therapy vs placebo in patients (pts) with high-risk locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT009.

Background: Treatment (tx) for LA SCCHN includes a combination of surgery, radiation and/or chemotherapy followed by monitoring for local recurrence/distant metastases as standard of care. Given poor outcomes, there remains a clear unmet need in this pt population. IMvoke010 (NCT03452137) evaluated the efficacy and safety of atezo in pts with LA SCCHN who are at high-risk for disease progression following multi-modal definitive tx. Methods: Eligible pts with LA SCCHN (Stage IVa or IVb involving the oral cavity, larynx, hypopharynx, HPV negative oropharynx or Stage III HPV positive oropharynx [per AJCC 8th edition]) with no disease progression after multi-modal definitive tx were randomized (1:1) to receive atezo 1200 mg or placebo. Tx was given every 3 weeks for 1 year or until disease progression, unacceptable toxicity or consent withdrawal. Primary endpoint: investigator-assessed event-free survival (INV-EFS). Other key endpoints: overall survival (OS, secondary for efficacy) and safety. Results: A total of 406 pts were randomized to receive either atezo (n=203) or placebo (n=203). 156 (38.4%) pts underwent surgery as part of definitive tx. At clinical cutoff (27 September 2023), median follow-up was 46.5 months (mos). Median INV-EFS was 59.5 mos with atezo vs 52.7 mos with placebo (HR, 0.94; 95% CI, 0.70-1.26). INV-EFS results were generally consistent across all subgroups. OS showed no difference between arms for atezo vs placebo. Safety data are reported (Table). Conclusion: This study did not meet the primary endpoint of INV-EFS, a numerical improvement in INV-EFS was observed for atezo in pts with LA SCCHN, but this was not statistically significant. Atezo was generally well tolerated, and no new safety signals were identified. Table: Key efficacy and safety results Efficacy Atezo (n=203)* Placebo (n=203) Median INV-EFS, mos 59.5 52.7 HR (95% CI) 0.94 (0.70-1.26) P-value 0.6804† Median OS, mos NE NE HR (95% CI) 0.96 (0.68-1.36) Safety, n (%) Grade 3-4 AEs 55 (27.2) 43 (21.2) TRAEs Grade 3-4 20 (9.9) 12 (5.9) Grade 5 AEs 3 (1.5) 5 (2.5) SAEs 32 (15.8) 32 (15.8) AEs leading to tx discontinuation 18 (8.9) 9 (4.4) CI, confidence interval; HR, hazard ratio; *safety-evaluable pts (n=202); †α boundary: 0.0427 Citation Format: Deborah J. Wong, Jérôme Fayette, Maria Teixeira, Kumar Prabhash, Ricard Mesia, Andrzej Kawecki, Arunee Dechaphunkul, José Dinis, Ye Guo, Muneyuki Masuda, Ching-Yun Hsieh, Maria Grazia Ghi, Claudia Vaz de Melo Sette, Tao Jiang, Yibing Yan, Monika Kaul, Ritika Jagtiani, Christina Matheny, Vaikunth Cuchelkar, Robert Haddad. IMvoke010: A phase III, double-blind randomized trial of atezolizumab (atezo) after definitive local therapy vs placebo in patients (pts) with high-risk locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT009.

PURPOSE CheckMate 651 (ClinicalTrials.gov identifier: NCT02741570 ) evaluated first-line nivolumab plus ipilimumab versus EXTREME (cetuximab plus cisplatin/carboplatin plus fluorouracil ≤ six cycles, then cetuximab maintenance) in recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). METHODS Patients without prior systemic therapy for R/M SCCHN were randomly assigned 1:1 to nivolumab plus ipilimumab or EXTREME. Primary end points were overall survival (OS) in the all randomly assigned and programmed death-ligand 1 combined positive score (CPS) ≥ 20 populations. Secondary end points included OS in the programmed death-ligand 1 CPS ≥ 1 population, and progression-free survival, objective response rate, and duration of response in the all randomly assigned and CPS ≥ 20 populations. RESULTS Among 947 patients randomly assigned, 38.3% had CPS ≥ 20. There were no statistically significant differences in OS with nivolumab plus ipilimumab versus EXTREME in the all randomly assigned (median: 13.9 v 13.5 months; hazard ratio [HR], 0.95; 97.9% CI, 0.80 to 1.13; P = .4951) and CPS ≥ 20 (median: 17.6 v 14.6 months; HR, 0.78; 97.51% CI, 0.59 to 1.03; P = .0469) populations. In patients with CPS ≥ 1, the median OS was 15.7 versus 13.2 months (HR, 0.82; 95% CI, 0.69 to 0.97). Among patients with CPS ≥ 20, the median progression-free survival was 5.4 months (nivolumab plus ipilimumab) versus 7.0 months (EXTREME), objective response rate was 34.1% versus 36.0%, and median duration of response was 32.6 versus 7.0 months. Grade 3/4 treatment-related adverse events occurred in 28.2% of patients treated with nivolumab plus ipilimumab versus 70.7% treated with EXTREME. CONCLUSION CheckMate 651 did not meet its primary end points of OS in the all randomly assigned or CPS ≥ 20 populations. Nivolumab plus ipilimumab showed a favorable safety profile compared with EXTREME. There continues to be a need for new therapies in patients with R/M SCCHN.

INTRODUCTION To date, there is no established optimal method for endoscopic detection of esophageal squamous cell neoplasia in high-risk individuals. OBJECTIVES We aimed to compare the performance of narrow-band imaging (NBI) and Lugol chromo-endoscopy in screening for esophageal neoplasia among patients with a history of treatment for head and neck squamous cell cancer (HNSCC). PATIENTS AND METHODS We randomly assigned 300 patients who had completed curative treatment for HNSCC at least 1 year prior to the inclusion to undergo either NBI or Lugol endoscopy (2:1 ratio). Follow-ing white-light examination of the esophagus, the assigned imaging study was performed, and biopsies were taken from any suspicious lesions identified using NBI or Lugol chromoendoscopy. The primary end point was positive predictive value (PPV) of the biopsied lesion for a diagnosis of esophageal neoplasia (high-grade intraepithelial neoplasia [HG-IEN] or invasive esophageal squamous cell carcinoma [ESCC]). The secondary end points included the number of biopsied lesions, duration of esophagus examination, and endoscopy tolerance. RESULTS In 294 patients included in the final analysis (NBI, n = 204; Lugol chromoendoscopy, n = 90), we diagnosed 3 ESCCs (1.02%) and 2 HG-IENs (0.68%). The PPV of NBI and Lugol chromoendoscopy in per-lesion analysis was 7.69% (95% CI, 0.94%-25.1%) and 8.11% (95% CI, 1.7%-21.9%), respectively (P >0.99). NBI outperformed Lugol chromoendoscopy in terms of the rate of patients requiring biopsy (12.75% vs 41.11%; P = 0.003), duration of esophagus examination (3.5 min vs 5.15 min; P <0.001), and endoscopy tolerance assessed on the visual analog scale (25 mm vs 36.5 mm; P = 0.002). CONCLUSIONS With a PPV comparable to that of Lugol chromoendoscopy, but a lower number of biopsies required, shorter examination time, and better patient tolerance, NBI could be considered the primary screening method for ESCC in patients with HNSCC.

The guidelines Thyroid Cancer 2022 are prepared based on previous Polish recommendations updated in 2018. They consider international guidelines - American Thyroid Association (ATA) 2015 and National Comprehensive Cancer Network (NCCN); however, they are adapted according to the ADAPTE process. The strength of the recommendations and the quality of the scientific evidence are assessed according to the GRADE system and the ATA 2015 and NCCN recommendations. The core of the changes made in the Polish recommendations is the inclusion of international guidelines and the results of those scientific studies that have already proven themselves prospectively. These extensions allow de-escalation of the therapeutic management in low-risk thyroid carcinoma, i.e., enabling active surveillance in papillary microcarcinoma to be chosen alternatively to minimally invasive techniques after agreeing on such management with the patient. Further extensions allow the use of thyroid lobectomy with the isthmus (hemithyroidectomy) in low-risk cancer up to 2 cm in diameter, modification of the indications for postoperative radioiodine treatment toward personalized approach, and clarification of the criteria used during postoperative L-thyroxine treatment. At the same time, the criteria for the preoperative differential diagnosis of nodular goiter in terms of ultrasonography and fine-needle aspiration biopsy have been clarified, and the rules for the histopathological examination of postoperative thyroid material have been updated. New, updated rules for monitoring patients after treatment are also presented. The updated recommendations focus on ensuring the best possible quality of life after thyroid cancer treatment while maintaining the good efficacy of this treatment.

Post-treatment follow-up is an essential component of comprehensive cancer care. Determining optimal follow-up schedules is crucial on clinical, organisational and economic grounds. Owing to the scarcity of prospective clinical follow-up trials, most recommendations are based on retrospective studies and expert opinions. In 2014, the first post­-treatment follow-up recommendations in the most common solid malignancies was published by Polish oncology and family medicine experts. In this article, we present an update of this document that takes into account the current literature and the quality of the available scientific evidence.

The guidelines Thyroid Cancer 2022 are prepared based on previous Polish recommendations updated in 2018. They consider international guidelines - American Thyroid Association (ATA) 2015 and National Comprehensive Cancer Network (NCCN); however, they are adapted according to the ADAPTE process. The strength of the recommendations and the quality of the scientific evidence are assessed according to the GRADE system and the ATA 2015 and NCCN recommendations. The core of the changes made in the Polish recommendations is the inclusion of international guidelines and the results of those scientific studies that have already proven themselves prospectively. These extensions allow de-escalation of the therapeutic management in low-risk thyroid carcinoma, i.e., enabling active surveillance in papillary microcarcinoma to be chosen alternatively to minimally invasive techniques after agreeing on such management with the patient. Further extensions allow the use of thyroid lobectomy with the isthmus (hemithyroidectomy) in low-risk cancer up to 2 cm in diameter, modification of the indications for postoperative radioiodine treatment toward personalized approach, and clarification of the criteria used during postoperative L-thyroxine treatment. At the same time, the criteria for the preoperative differential diagnosis of nodular goiter in terms of ultrasonography and fine-needle aspiration biopsy have been clarified, and the rules for the histopathological examination of postoperative thyroid material have been updated. New, updated rules for monitoring patients after treatment are also presented. The updated recommendations focus on ensuring the best possible quality of life after thyroid cancer treatment while maintaining the good efficacy of this treatment.

INTRODUCTION: As the changes leading to improvement of cancer care in Poland have shown the need to introduce clinical practice guidelines into the health care system, it has become clear that no methodological standard of the process for guidelines preparation has been established so far. The following process aims to present a unified and comprehensive clinical practice guidelines (CPGs) development methodology. MATERIALS AND METHODS: A review of globally recognised methods used by guideline development groups was prepared, informing the discussion during three plenary meetings and extensive consultations in writing. The resulting document was unanimously approved by a group of 24 methodologists and clinical experts, and has been formally recognized as a standard for CPGs development by the management of the National Institute of Oncology and the Agency for Health Technology Assessment and Tariff System. RESULTS: Within the process, 43 recommendations were formulated to create unified and comprehensive rules for guideline development within the Polish healthcare system. CONCLUSIONS: The presented methods are consistent with the globally recognized tools and methods of guideline development, such as GRADE and ADAPTE, and follow quality criteria described by AGREE II. The process supports the development of high-quality guidelines within a resource-constrained setting by allowing to choose between adoption, adaptation, or de novo development of either the whole document of guidelines or particular recommendations.

The treatment of locally advanced head and neck cancer (HNC) is based on extensive resections followed by concurrent chemoradiotherapy (CRT) with platinum derivatives or concurrent radiotherapy with cetuximab (bioradiotherapy; BRT). Malnutrition, which occurs in up to 60% of patients before treatment commencement, severely increases the risk of CRT/BRT drug dose reductions and the incidence of treatment-related adverse events. A prospective observational study was performed regarding the influence of nutritional care on nutritional status, compliance with the treatment’s planned regimen, and the incidence of treatment-related complications in patients with advanced HNC during CRT and BRT. The study population encompassed 153 patients compared with a retrospective control group of 72 patients treated before nutritional care was included in the standard of oncological care. Patients enrolled in the nutritional care programme received significantly higher doses of platinum derivatives or cetuximab than patients in the control group. A significant difference between the compared populations was observed in patients below 70 years of age (92.8% of the study population), after prior surgery, and with initial weight loss lower than 10%. Nutritional care reduced final weight loss and prevented a decline within the laboratory markers of nutritional status. Weight loss was comparable in both modes of treatment—CRT and BRT. The incidence of treatment-related complications was significantly higher in patients without nutritional support in the subgroups of patients under 70 years of age and after primary surgery. Nutritional care before and during CRT and BRT in patients with HNC is a determinant of therapeutic benefit, defined as preventing down-dosing, weight loss, and the incidence of complications. Platinum derivatives and cetuximab had comparable influence on weight loss.

Background: The aim of the RESGEX study was to compare the efficacy and safety of the anti-epidermal growth factor receptor (anti-EGFR) antibody tomuzotuximab against cetuximab both in combination with chemotherapy in patients with recurrent and/or metastatic squamous cell cancer of the head and neck in the first-line treatment. Patients and methods: In this phase II trial 240 patients were equally randomized for six cycles to receive either tomuzotuximab (initial dose 990 mg then 720 mg) weekly and cisplatin 100 mg/m(2) and fluorouracil (5-FU; 1000 mg/m(2)/day, days 1-4) every 3 weeks or cetuximab (400 mg/m(2) subsequent 250 mg/m(2)) weekly with the same chemotherapeutic backbone followed by antibody maintenance treatment. The primary endpoint was progression-free survival. Results: Median progression-free survival was 6.5 months [95% confidence interval (CI) 5.9-7.9 months] in the tomuzotuximab group and 6.2 months (95% CI 5.8-7.3 months) in the cetuximab group (P = 0.86). The median overall survival (OS) estimate was 11.6 months (95% CI 9.5-17.2 months) in the tomuzotuximab group and 13.8 months (95% CI 12.3-16.4 months) in the cetuximab group (P = 0.96). In an exploratory analysis a small subgroup of p16-positive patients had a significantly longer OS compared with p16-negative patients (hazard ratio 1.860, 95% CI 1.09-3.16, P = 0.02). Conclusions: The glyco-engineered antibody tomuzotuximab failed to demonstrate improved efficacy with a chemotherapeutic backbone in the first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma. It remains a so far unanswered question whether such antibody would partner better with different drugs such as checkpoint inhibitors.

Soft tissue and bone sarcomas are a group of rare, heterogeneous, high-mortality cancers, each with a different biology and clinical course. They constitute 20% of all childhood cancers and about 1% of all adult malignancies. Advanced pathomorphological-molecular diagnostics using classic methods is often insufficient to make the final diagnosis, and thus implement the right therapy. In these cases, next generation sequencing technology (NGS) is helpful, which allows for analysis of many genes and classes of mutations in one assay with minimal consumption of tissue material. Wide genetic profiling enables, in many cases, not only to make the correct diagnosis, but also to identify potential therapeutic goals for modern targeted therapies in oncology. In this paper, we present recommendations on the use of the NGS method in advanced genetic diagnosis of sarcomas in adults, children and adolescents.

Adenoic cystic carcinoma (SACC, ACC) in the head and neck area, occurring in small and large salivary glands are relatively rare tumors, usually undergoing slow progression. ACC is characterized by a different clinical course compared to other cancers, with a long latency period, a tendency to form late, initially asymptomatic metastases and a small percentage of responses to systemic treatment. This article presents current recommendations for diagnostic procedures and treatment possibilities.

Adenoic cystic carcinoma (SACC, ACC) in the head and neck area, occurring in small and large salivary glands are relatively rare tumors, usually undergoing slow progression. ACC is characterized by a different clinical course compared to other cancers, with a long latency period, a tendency to form late, initially asymptomatic metastases and a small percentage of responses to systemic treatment. This article presents current recommendations for diagnostic procedures and treatment possibilities.