Postoperative adjuvant radiochemotherapy with cisplatin versus adjuvant radiochemotherapy with cisplatin and pembrolizumab in locally advanced head and neck squamous cell carcinoma- the study protocol of the Adrisk trial.

Most of the patients with head and neck squamous cell carcinoma (HNSCC) are diagnosed with locally advanced disease. Standards of care for curative-intent treatment of this patient group are either surgery and adjuvant radio(chemo)therapy (aRCT) or definitive chemoradiation. Despite these treatments, especially pathologically intermediate and high-risk HNSCC often recur. The ADRISK trial investigates in locally advanced HNSCC and intermediate and high risk after up-front surgery if the addition of pembrolizumab to aRCT with cisplatin improves event-free sur-vival compared to aRCT alone. ADRISK is a prospective, randomized controlled investiga-tor-initiated (IIT)-phase II multicenter trial within the German Interdisciplinary Study Group of German Cancer Society (IAG-KHT). Patients with primary resectable stage III and IV HNSCC of the oral cavity, oropharynx, hypopharynx and larynx with pathologic high (R1, extracapsular nodal extension) or intermediate risk (R0 <5 mm; N≥2) after surgery will be eligible. Two hun-dred forty patients will be randomly assigned (1:1) to either standard aRCT with cisplatin (standard arm) or aRCT with cisplatin + pembrolizumab (200 mg iv, in 3-week cycle, max. 12 months) (interventional arm). Endpoints are event-free and overall survival. Recruitment started in August 2018 and is ongoing.

[Updated S2k AWMF guideline on obstructive sialadenitis]. / Aktualisierte AWMF-S2k-Leitlinie zur obstruktiven Sialadenitis.

The update of this guideline was an important step to define standards for the use of sialendoscopy and other emerging minimally invasive techniques for the therapy of sialolithiasis and other obstructive salivary gland diseases. The current actualization was necessary to adapt the diagnostic and therapeutic algorithms to the current scientific knowledge. In this article they are presented in a shortened version with a focus on conservative therapeutic measures which are especially relevant for daily practice.

Accelerated Fractionation Plus Chemotherapy Versus Conventionally Fractionated Radiochemotherapy for Unresectable Head-and-Neck Cancer.

BACKGROUND/AIM: Prognosis of patients with unresectable squamous cell carcinomas of the head and neck requires improvement. This retrospective study compared accelerated radiotherapy plus chemotherapy to conventional radiochemotherapy. PATIENTS AND METHODS: Patients received definitive treatment with accelerated radiotherapy plus chemotherapy (group A, n=10) or conventional cisplatin-based radiochemotherapy (group B, n=85). Groups were matched for several patient and tumor characteristics and compared for locoregional control (LRC), overall survival (OS) and toxicities. Additionally, accelerated radiotherapy plus chemotherapy and chemotherapy regimens in group B were compared for LRC and OS. RESULTS: Treatment type had no significant impact on LRC (p=0.98) and OS (p=0.57). In group A, toxicities occurred more often, including grade ≥3 mucositis (p=0.041), grade ≥2 lymphedema (p=0.007) and grade ≥3 leucopenia (p=0.007). Best 2-year LRC (p=0.39) and OS (p=0.015) was achieved with 20 mg/m2 cisplatin days 1-5 every 4 weeks; accelerated radiochemotherapy resulted in second-worst outcomes. CONCLUSION: Given the limitations of this study, accelerated radiotherapy plus chemotherapy provided no significant benefit but increased toxicity compared to conventional radiochemotherapy.

Laryngeal chondrosarcoma with unusual dissemination to the humerus.

We report the case of an 81-year-old woman admitted to our clinic with a 16-month history of hoarseness due to unilateral vocal cord immobilization, slowly progressive dysphagia and an episode of painless swelling of the right arm. Radiological and histological workup revealed a medium-grade conventional chondrosarcoma of the cricoid cartilage with paratracheal spread and dissemination to the lung and the humeral bone. To our knowledge, this is the first humeral bone metastasis of laryngeal chondrosarcoma reported in the literature. The course of the presented case underlines the need for an early and detailed clinical and radiological workup of vocal cord immobilization.

Induction chemotherapy with paclitaxel and cisplatin followed by radiotherapy for larynx organ preservation in advanced laryngeal and hypopharyngeal cancer offers moderate late toxicity outcome (DeLOS-I-trial).

A prospective multicenter phase-II trial (12 centers) was performed by the German larynx organ preservation group (DeLOS) to evaluate the effect of induction chemotherapy (ICHT) with paclitaxel/cisplatin (TP), followed by accelerated-hyperfractionated (concomitant boost) radiotherapy (RT) in responders. The trial was focused on larynx preservation, tumor control, survival, salvage surgery and late toxicity in patients with advanced larynx/hypopharynx carcinoma eligible for total laryngectomy (LE). Seventy-one patients (40 larynx, 87.5% St. III, IV; 31 hypopharynx, 93.4% St. III, IV) were enrolled into the study and treated with ICHT (200 mg/m(2) paclitaxel, 100 mg/m(2) cisplatin; day 1, 22) according to the DeLOS protocol. Patients with complete or partial tumor response proceeded to RT (69.9 Gy in 5.5 weeks). Non-responders received a LE followed by postoperative RT (56-70 Gy in 5.5-7 weeks). The response rate to ICHT for larynx cancer was 69.6% (7.1% complete, 62.5% partial response) and for hypopharyngeal cancer was 84.3% (6.9% complete, 77.4% partial response). Overall survival after 36 months was 60.3% (95% CI, 48.4-72.2%), after 42 months was 56.5% (95% CI, 44.2-68.8%). Laryngectomy-free survival was as follows: after 36 months, 43.0% (95% CI, 30.9-55.0%); after 42 months, 41.3% (95% CI, 29.3-53.3%). Both parameters did not show different outcomes after distinguishing larynx from hypopharynx. LE was indicated in 15 non-responders after ICHT. Five of the 15 non-responders refused the laryngectomy. Two of the five received RT instead and had no evidence of disease 42 months after RT. Late toxicity (dysphagia III, IV LENT SOMA score in laryngectomy-free survivors: after 6 months, 1.8%; 12 months, 11.4%; 18 months, 14.5%; 24 months, 8.1%; 36 months, 16%) and salvage surgery (4 pharyngocutaneous fistulas in 27 operations) were tolerable. In a large portion of patients eligible for LE, the larynx could be preserved with satisfying functional outcome. Good responders after ICHT had also a good general outcome with relatively rare severe late toxicities. Due to a slight increase of relevant late dysphagia, functional outcome regarding swallowing and tracheotomy free breathing should be more focused in future larynx organ preservation trials.

[Surgical treatment options in laryngeal and hypopharyngeal cancer]. / Indikationen zur chirurgischen Therapie von Larynx- und Hypopharynxkarzinomen.

In Austria, around ten new cases of laryngeal cancer can currently be expected per 100.000 persons each year whereas three out of 100.000 men develope hypopharyngeal cancer. Among women, the incidence in both types of carcinoma is lower by a factor of around 5. All in all, the rate of new cases seems to have been constant or to have slightly decreased in the last few years. Approximately 70% of all laryngeal cancer are glottic cancer, that is to say originating from the vocal cords. About 30% are supraglottic tumours, true subglottic cancers are very rare. The majority of hypopharyngeal tumours originate from the piriform sinuses. Vocal cord tumours lead to a typical symptom that can be early detected: hoarseness. Thus, voice problems in adults that persist for several weeks should therefore always checked by laryngoscopy. This leads to there being a real possibility of early diagnosis of laryngeal cancer, which means that today, approximately 60% of all laryngeal tumours can be diagnosed in stage I or II according to UICC or as intraepithelial lesions (former carcinoma in situ). In glottic cancer about 75% are diagnosed in these early stages, whereas in supraglottic tumours the rate is only about 30% and in hypopharyngeal cancer it is less then 15%. Surgery, radiation therapy, chemo- or immunotherapy are the principal types of oncological treatments currently available. The following conditions generally need to be met for curative surgical treatment options: Local tumour, no systemic metastasis Tumour has to be resectable in healthy margins mortality/morbidity Surgery must not lead to unreasonable mutilation Lack of other therapeutic alternatives having an equal or lesser impact In the following pages, indications for the surgical treatment of laryngeal and hypopharyngeal cancer will be discussed and the results of surgical therapy will be summarised briefly.

False-positive uptake of I-131 in a laryngocele mimicking thyroid remnant after thyroidectomy for papillary thyroid carcinoma.

A 66-year-old woman underwent total thyroidectomy for papillary thyroid carcinoma stage pT4 followed by radioiodine therapy with 3.7 GBq (100 mCi) iodine-131. Radioiodine therapy revealed intense radioiodine uptake of the neck, which was interpreted as thyroid remnant tissue. Follow-up whole-body scans with iodine-131 in hypothyroidism 3 months and 1 year after radioiodine therapy revealed focal uptake in the neck. Computed tomography and gadolinium-enhanced MRI of the neck demonstrated an ovoid lesion in the larynx without gadolinium enhancement. Neither thyroid remnant tissue nor enlarged cervical lymph nodes could be demonstrated either on CT or on MRI. Further examination of the patient in the ear, nose and throat department confirmed the finding of a laryngocele and biopsies demonstrated benign tissue. Follow-up whole-body scans with iodine-131 in hypothyroidism 3 years and after injection of rhTSH 5 years after radioiodine therapy reproduced the focal uptake in the neck. After initial radioiodine therapy thyroglobulin levels were never measurable, not at any of the whole-body scans in hypothyroidism, after rhTSH, or at intermediate follow-up examinations under TSH-suppressive levothyroxine therapy. The patient declined definitive operative revision of the laryngocele and is in good health 8 years after the diagnosis of papillary thyroid carcinoma.

Voriconazole brain tissue levels in rhinocerebral aspergillosis in a successfully treated young woman.

Invasive aspergillosis of the central nervous system has a mortality rate exceeding 90%. We describe a 29-year-old woman with a medical history of chronic polyarthritis who developed a proven rhinocerebral Aspergillus fumigatus infection refractory to first-line treatment with liposomal amphotericin B. The patient responded successfully to salvage combination treatment with voriconazole and caspofungin. Furthermore, for the first time, voriconazole levels in an intracerebral abscess were measured in this patient undergoing voriconazole oral therapy.

Successful adjuvant tamoxifen therapy for estrogen receptor-positive metastasizing sweat gland adenocarcinoma: need for a clinical trial?

We report on successful adjuvant tamoxifen therapy for a metastasizing sweat gland adenocarcinoma of the scalp in a 64-year-old woman. Before the antihormonal therapy, the patient had undergone repeated surgery for ipsilateral intraparotid, soft tissue, and lymph node metastases and had had disease-free intervals of less than 5 months. As the immunohistochemical analysis of the tumor tissue revealed a 100% nuclear reactivity to estrogen and progesterone receptors, we started empirical tamoxifen citrate therapy, which dramatically changed the course of the disease. The patient has been in complete remission for 3 years. This is the third report in the literature of substantial therapeutic benefit of antiestrogen therapy in metastasizing eccrine gland adenocarcinoma with positive hormone receptor immunohistochemistry. We suggest examining the hormone receptor expression in these neoplasms regularly. A prospective study should be commenced to assess the benefit of adjuvant antihormonal therapy in eccrine gland adenocarcinomas.

High incidence of lymph node metastasis in major salivary gland cancer.

OBJECTIVE: To analyze the incidence and risk factors for clinically apparent and occult lymph node metastases in patients with major salivary gland cancers. DESIGN: Cohort of patients with a median follow-up of 46 months (range, 1-174 months). SETTING: University-based referral center. PATIENTS: A total of 160 consecutive patients with complete clinical and pathologic data. INTERVENTION: Neck dissection was performed in all cases. Patients were treated with surgery alone (55%); surgery and radiation therapy (43%); or a combination of surgery, radiation, and chemotherapy (2%). MAIN OUTCOME MEASURE: Incidence of apparent and occult lymph node metastases. Univariate and multivariate analyses were used to evaluate the significance of clinical and pathologic data. RESULTS: Histologically confirmed positive neck was found in 53% of all cases. Histologic diagnosis was significantly related to the incidence of lymph node metastasis: 89% (16/18) for undifferentiated carcinomas. However, so-called low-risk tumors had incidence rates of 22% to 47%. Twenty-one patients (13%) presented with clinically apparent cervical lymph node metastasis. Of the 139 patients with clinical N0 neck, 45% had occult neck metastasis. Neck metastasis was found in 29% (10/34) of T1, 54% (38/70) of T2, 65% (20/31) of T3, and 54% (16/25) of T4 tumors. Assessment of survival according to nodal status revealed significant correlations for overall (P<.001) and disease-free survival (P<.001). CONCLUSIONS: We found a high incidence of lymph node metastasis from major salivary gland cancers. Neck dissections should be considered as an integral part of the surgical approach in patients with major salivary gland cancer, especially if no postoperative radiation therapy is planned.