Optimizing the structure of interdisciplinary tumor boards for effective cancer care.

Introduction: Multi-professional interdisciplinary tumor boards (ITB) are essential institutions to discuss all newly diagnosed, relapsed or complex cancer patients in a team of specialists to find an optimal cancer care plan for each individual patient with regard to national and international clinical practice guidelines, patient´s preference and comorbidities. In a high-volume cancer center, entity-specific ITBs take place at least once a week discussing a large number of patients. To a high level of expertise and dedication, this also requires an enormous amount of time for physicians, cancer specialists and administrative support colleagues, especially for radiologists, pathologists, medical oncologists and radiation oncologists, who must attend all cancer-specific boards according to certification requirements. Methods: In this 15-month prospective German single-center analysis, we examined the established structures of 12 different cancer-specific ITBs at the certified Oncology Center and demonstrate tools helping to optimize processes before, during and after the boards for optimal, time-saving procedures. Results: By changing pathways, introducing revised registration protocols and new digital supports we could show that the workload of preparation by radiologists and pathologists could be reduced significantly by 22.9% (p=<0.0001) and 52.7% (p=<0.0001), respectively. Furthermore, two questions were added to all registration forms about the patient´s need for specialized palliative care support that should lead to more awareness and early integration of specialized help. Discussion: There are several ways to reduce the workload of all ITB team members while maintaining high quality recommendations and adherence to national and international guidelines.

Isolated congenital tracheal stenosis in a preterm newborn.

Severe tracheal stenosis, resulting in functional atresia of the trachea is a rare congenital malformation with an estimated occurrence of two in 100,000 newborns. If no esophagotracheal fistula is present to allow for spontaneous breathing, this condition is usually fatal. We report on a male infant born at 32 weeks of gestation. The patient presented with respiratory distress immediately after delivery due to severe congenital tracheal stenosis resulting in functional atresia of the trachea. Endotracheal intubation failed and even emergency tracheotomy did not allow ventilation of the patient lungs. The patient finally succumbed to prolonged hypoxia due to functional tracheal atresia. The etiology of tracheal atresia and tracheal stenosis is still unclear, but both conditions are frequently combined with other anomalies of the VACTERL (vertebral anomalies, anal atresia, cardiovascular anomalies, tracheoesophageal fistula, esophageal atresia, renal/radial anomalies and limb defects) and TACRD (tracheal agenesis, cardiac, renal and duodenal malformations) association. Conclusion Successful treatment of severe congenital tracheal stenosis and tracheal atresia depends on either prenatal diagnosis or recognition of this condition immediately after birth to perform tracheotomy without delay. Nevertheless, despite any efforts, the therapeutical results of severe tracheal stenosis and tracheal atresia are still unsatisfactory.

Analysis of chemokine and chemokine receptor expression in squamous cell carcinoma of the head and neck (SCCHN) cell lines.

The purpose of this work was to analyze chemokine and chemokine receptor expression in untreated and in irradiated squamous cell carcinoma of the head and neck (SCCHN) tumor cell lines, aiming at the establishment of assays to test for the relevance of chemokine and chemokine receptor expression in the response of SCCHN to radiotherapy and radiochemotherapy. Five low passage and 10 established SCCHN lines, as well as two normal cell lines, were irradiated at 2 Gy or sham-irradiated, and harvested between 1 and 48 h after treatment. For chemokines with CC and CXC structural motifs and their receptors, transcript levels of target and reference genes were quantified relatively by real-time PCR. In addition, CXCL1 and CXCL12 protein expression was analyzed by ELISA. A substantial variation in chemokine and chemokine receptor expression between SCCHN was detected. Practically, all cell lines expressed CCL5 and CCL20, while CCL2 was expressed in normal cells and in some of the tumor cell lines. CXCL1, CXCL2, CXCL3, CXCL10, and CXCL11 were expressed in the vast majority of the cell lines, while the expression of CXCL9 and CXCL12 was restricted to fibroblasts and few tumor cell lines. None of the analyzed cell lines expressed the chemokines CCL3, CCL4, or CCL19. Of the receptors, transcript expression of CCR1, CCR2, CCR3, CCR5, CCR7, CCXR2, and CCXR3 was not detected, and CCR6, CXCR1, and CXCR4 expression was restricted to few tumor cells. Radiation caused up- and down-regulation with respect to chemokine expressions, while for chemokine receptor expressions down-regulations were prevailing. CXCL1 and CXCL12 protein expression corresponded well with the mRNA expression. We conclude that the substantial variation in chemokine and chemokine receptor expression between SCCHN offer opportunities for the establishment of assays to test for the relevance of chemokine and chemokine receptor expression in the response of SCCHN to radiotherapy and radiochemotherapy.

Nasopharyngeal carcinoma in adults: treatment results after long-term follow-up with special reference to adjuvant interferon-beta in undifferentiated carcinomas.

PURPOSE: Nasopharyngeal carcinomas (NPC) are radiosensitive, and radiotherapy is the standard curative treatment. Furthermore, it has been shown that combined radiochemotherapy improves prognosis in locally advanced stages. Further encouraging results have been obtained with adjuvant interferon-beta after primary radio(chemo)therapy in childhood undifferentiated NPC. Aim of the present study was to evaluate the treatment results after long-term follow-up after radio(chemo)therapy for adult NPC with special reference to patients with undifferentiated carcinomas treated with adjuvant interferon-beta. PATIENTS AND METHODS: From 02/1992 to 07/2008, 26 adult patients with NPC without distant metastases were treated (17 squamous cell carcinomas, 9 undifferentiated carcinomas). The treatment concepts changed over the years: 13 patients were treated with radiotherapy alone, 13 patients received combined radiochemotherapy. Additionally, six patients with undifferentiated carcinomas were treated with adjuvant interferon-beta after radiochemotherapy for 6 months. RESULTS: After a median follow-up of 96 months, 17 patients remain alive. Collectively, our 5-year overall-survival and loco-regional control rates were 74% (radiochemotherapy 81%, radiotherapy alone 68.5%) and 87% (radiochemotherapy 100%, radiotherapy alone 72.7%), respectively. All treatment regimens used were feasible; especially, adjuvant interferon-beta was applied as provided without high grade toxicity. All patients with undifferentiated carcinomas treated with adjuvant interferon-beta stayed alive until the end of the follow-up. CONCLUSION: In summary, our data affirm that NPC in adults are curable by primary radio(chemo)therapy. Furthermore, our data indicate that adjuvant interferon-beta application in undifferentiated NPC in adults is feasible and shows promising results. Further prospective clinical trials are needed to finally establish adjuvant interferon beta in curative treatment of adult NPC.

Impact of distant metastasis in patients with cervical lymph node metastases from cancer of an unknown primary site.

OBJECTIVES: Treatment methods for patients with cervical cancer of an unknown primary site (CUP) are still under discussion. The purpose of this retrospective study was to analyze the oncological follow-up of 58 patients treated for cervical CUP. METHODS: From 1986 to 2006, 58 patients with cervical CUP were treated at the authors' institution. Treatment consisted of neck dissection alone in 8, irradiation or chemoradiation in 5, combined surgery and radiotherapy in 28, and surgery and radiochemotherapy in 17. RESULTS: The 3-year and 5-year overall survival rates for all patients were 52.9% and 40.9%, respectively. The 3-year and 5-year disease-specific survival rates were 50.9% and 39.7%, respectively. The 3-year and 5-year neck control rates were 73.7% and 67.3%, respectively. Neck dissection followed by radiochemotherapy was associated with the best 3-year and 5-year locoregional control rates. Extracapsular extension was a predictor of survival, but not of neck control. Distant metastases developed in about one third of all patients and were the most frequent cause of tumor-related death in cases of advanced neck disease. CONCLUSIONS: Despite the fact that regional control can be achieved in many cases, survival rates may be limited by distant metastasis, especially in patients with advanced neck disease.

Organ function and quality of life after transoral laser microsurgery and adjuvant radiotherapy for locally advanced laryngeal cancer.

BACKGROUND AND PURPOSE: Transoral laser microsurgery (TLM) and adjuvant radiotherapy are an established therapy regimen for locally advanced laryngeal cancer at our institution. Aim of the present study was to assess value of quality of life (QoL) data with special regard to organ function under consideration of treatment efficacy in patients with locally advanced laryngeal cancer treated with larynx-preserving TLM and adjuvant radiotherapy. PATIENTS AND METHODS: From 1994 to 2006, 39 patients (ten UICC stage III, 29 UICC stage IVA/B) with locally advanced laryngeal carcinomas were treated with TLM and adjuvant radiotherapy. Data concerning treatment efficacy, QoL (using the VHI [Voice Handicap Index], the EORTC QLQ-C30 and QLQ-H&N35 questionnaires) and organ function (respiration, deglutition, voice quality) were obtained for ten patients still alive after long-term follow-up. Correlations were determined using the Spearman rank test. RESULTS: After a median follow-up of 80.8 months, the 5-year overall survival rate was 46.8% and the locoregional control rate 76.5%, respectively. The larynx preservation rate was 89.7% for all patients and 100% for patients still alive after follow-up. Despite some verifiable problems in respiration, speech and swallowing, patients showed a subjectively good QoL. CONCLUSION: TLM and adjuvant radiotherapy is a curative option for patients with locally advanced laryngeal cancer and an alternative to radical surgery. Even if functional deficits are unavoidable in the treatment of locally advanced laryngeal carcinomas, larynx preservation is associated with a subjectively good QoL.

Endoscopic laser surgery of early glottic cancer: involvement of the anterior commissure.

BACKGROUND: Early glottic cancer can be cured with transoral laser resection, but in cases with anterior commissure involvement, there is still controversy concerning the best treatment modality. METHODS: The impact of anterior commissure involvement on local control was analyzed in a retrospective review of 444 patients with early glottic cancer (pT1a-pT2a) treated between 1986 and 2004 with transoral laser microsurgical resection. RESULTS: The anterior commissure was involved in 153 cases; the 5-year local control rate with and without anterior commissure involvement was 73% versus 89% for T1a and 68% versus 86% for T1b tumors. For T2a lesions, the 5-year local control rate was 76%, irrespective of anterior commissure involvement. CONCLUSION: In early glottic cancer treated by transoral laser microsurgery, a decrease in local control is evident in case of anterior commissure involvement for T1a and T1b but not for T2a tumors.

Impact of anterior commissure involvement on local control of early glottic carcinoma treated by laser microresection.

OBJECTIVES: To analyze the impact of anterior commissure involvement on local control, survival, and laryngeal preservation in patients with early glottic cancer (pT1a-pT2a) treated with unimodality laser microsurgical resection. STUDY DESIGN: Retrospective review of 263 patients with early glottic cancer treated between 1986 and 1996. METHODS: Data on local control and overall survival rates were analyzed and calculated by the Kaplan-Meier method; the larynx preservation rates were given absolutely. RESULTS: Among 158 patients presenting with T1a glottic cancer, the anterior commissure was involved in 28 cases; the 5-year local control rate was 84%, and the larynx preservation rate was 93%. In the 130 cases without anterior commissure involvement, the 5-year local control rate was 90.0% and the corresponding larynx preservation rate 99%. In the T1b category consisting of 30 patients, anterior commissure involvement was observed in 16 patients; the 5-year local control rate was 73%, and the larynx preservation rate was 88%. In the 14 cases without anterior commissure involvement, the 5-year local control rate was 92% and the corresponding larynx preservation rate 100%. Seventy-five patients had T2a glottic carcinomas, with normal vocal cord movement. The anterior commissure was involved in 45 cases; the 5-year local control rate was 79%, and the larynx preservation rate was 93%. In the 30 cases without anterior commissure involvement, the 5-year local control rate was 74.0% and the corresponding larynx preservation rate 97%. CONCLUSIONS: This study shows the effectiveness of laser microsurgery for early glottic carcinoma regardless of anterior commissure involvement at presentation. This method can be performed as an outpatient procedure, even when conducting reresections.

Human cortical motor representation of the larynx as assessed by transcranial magnetic stimulation (TMS).

OBJECTIVES: To analyze characteristic features and details on motor-evoked potentials (MEPs) of the cricothyroid and vocalis muscles from single-pulse cortical transcranial magnetic stimulation (TMS) in normal subjects to characterize cortical motor representation of laryngeal muscles. STUDY DESIGN: Prospective, experimental investigation on healthy volunteers. METHOD: MEPs of the cricothyroid and vocalis muscles elicited by cortical TMS with a figure-8-shaped coil were investigated in two groups of six healthy subjects each, with special regard to MEP amplitude as a function of the coil position on the head surface along the interaural line. RESULTS: Bilateral reproducible responses of the cricothyroid and the vocalis muscles could be observed in all subjects. For the cricothyroid muscle, maximal responses were obtained at mean stimulus positions of 7.5 +/- 1.4 cm (contralateral) and of 7.3 +/- 1.3 cm (ipsilateral), respectively. For the vocalis muscle, we found maximal responses at mean stimulus positions of 10.3 +/- 1.9 cm (contralateral) and of 9.6 +/- 1.6 cm (ipsilateral), respectively. Despite a considerable overlap of these coil positions, from which reproducible MEPs could be elicited in both groups of the laryngeal muscles, statistically significant separation of the cricothyroid-and vocalis-associated cortical representation areas was possible. CONCLUSIONS: Our observations point to two different cortical motor representation areas, with the cricothyroid muscle-related area being located more medially.

Bilateral changes in cortical motor representation of the tongue after unilateral peripheral facial paralysis: evidence from transcranial magnetic stimulation.

Motor evoked potentials of the lingual muscles due to focal cortical transcranial magnetic stimulation were investigated in 5 patients with unilateral total facial paralysis with regard to amplitude as a function of the coil position on the interaural line. Maximum bilateral responses could be obtained at mean stimulus positions of about 6 to 8 cm lateral to the vertex. In comparison with healthy subjects, the patient group had significantly smaller mediolateral calculated centers for ipsilateral and contralateral responses. At the optimum stimulus positions, the patients' mean motor evoked potential amplitudes were significantly lower than those in healthy subjects. These alterations could be observed on both cortical hemispheres, but were more pronounced for the hemisphere contralateral to the side of facial paralysis. Thus, we provide strong evidence of bilateral changes in lingual cortical motor representation following facial paralysis with an invasion of the facial motor area by the tongue motor representation.

Tongue representation in the lateral cortical motor region of the human brain as assessed by transcranial magnetic stimulation.

Motor evoked potentials (MEPs) of the lingual muscles elicited by focal cortical transcranial magnetic stimulation (TMS) with a figure 8-shaped coil were investigated in 17 healthy subjects with special regard to amplitude and onset latency as a function of the coil position on the head surface. Bilateral reproducible responses could be observed at coil positions mostly varying from approximately 6 to 13 cm lateral to the vertex. During moderate muscle activation, maximum responses were obtained at a mean stimulus position of about 11 cm lateral and 3 cm anterior to the vertex with similar onset latencies, but with significantly higher amplitudes on the contralateral side (3.5 +/- 1.9 mV, 9.5 +/- 1.1 ms contralateral; 2.6 +/- 1.5 mV, 9.7 +/-1.0 ms ipsilateral). Comparing our data on the orbicularis oculi muscle with the results obtained on lower lip muscles, we found a considerable overlap of those coil positions from which reproducible MEPs could be elicited in both groups of target muscles, but the lingual area was placed more laterally. Thus, a statistically significant separation of the cortical representation areas of lingual and lower lip mimetic muscles is possible by focal cortical TMS, reflecting somatotopic organization of the face-associated motor cortex.

Surgical and nonsurgical treatment options in patients with movement disorders of the platysma.

PURPOSE: Movement disorders of the platysma may constitute both an aesthetic and a functional problem for the affected patients, who almost always have hyperkinesis. This article describes the different treatment options for movement disorders of the platysma. PATIENTS AND METHODS: The therapeutic options that we used involved surgical and nonsurgical strategies (33 patients), including neurectomy of the cervical branch of the facial nerve, myectomy of the platysma, and the injection of botulinum toxin A. After therapy, patients were evaluated through self-assessment of the clinical outcome, clinical examination, and electromyography. RESULTS: All patients showed improvement or complete alleviation of their symptoms. The data also showed that resection of the cervical branch of the facial nerve after its anterograde neurolysis may be performed during facial nerve reconstruction. CONCLUSIONS: The various nonsurgical and surgical strategies are suitable for the treatment of different forms of platysmal movement disorders.