Oncologic outcome with versus without target volume compartmentalization in postoperative radiotherapy for oral cavity squamous cell carcinoma.

Background and purpose: The volume treated with postoperative radiation therapy (PORT) in patients with oral cavity squamous cell carcinoma (OCSCC) is a mediator of toxicity affecting quality of life. Current guidelines only allow for very limited reduction of PORT volumes. This study investigated the safety and efficacy of de-intensified PORT for patients with OCSCC by refined compartmentalization of the treatment volume. Materials and methods: This retrospective cohort study identified 103 OCSCC patients treated surgically from 2014 to 2019 with a loco-regional risk profile qualifying for PORT according to guidelines. PORT was administered only to the at-risk compartment and according to a refined compartmentalization concept (CC). Oncological outcome of this CC cohort was compared to a historical cohort (HC) of 98 patients treated before the CC was implemented. Results: Median follow-up time was 4.5 and 4.8 years in the CC and HC cohorts, respectively. In the CC cohort, a total of 72 of 103 patients (70%) had a pathological risk profile that allowed for further compartmentalization and, hence, received a reduced treatment volume or omission of PORT altogether. Loco-regional control at 3 and 5 years was 77% and 73% in the CC cohort versus 78% and 73% in the HC (p = 0.93), progression-free survival was 72% and 64% versus75% and 68% (p = 0.58), respectively. Similarly, no statistically significant difference was seen in other outcome measures. Conclusions: De-intensified PORT limiting the treatment volume to the at-risk compartment or avoiding PORT altogether for low-risk patients with OCSCC does not seem to compromise disease control in this retrospective comparison. Based on these hypothesis-generating findings, a prospective study is being planned.

A multi-centric dataset on patient-individual pathological lymph node involvement in head and neck squamous cell carcinoma.

Dataset: We provide a dataset on lymph node metastases in 968 patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC). All patients received neck dissection and we report the number of metastatic versus investigated lymph nodes per lymph node level (LNL) for every individual patient. Additionally, clinicopathological factors including T-category, primary tumor subsite (ICD-O-3 code), age, and sex are reported for all patients. The data is provided as three datasets: Dataset 1 contains 373 HNSCC patients treated at Centre Léon Bérard (CLB), France, with primary tumor location in the oral cavity, oropharynx, hypopharynx, and larynx. Dataset 2 contains 332 HNSCC patients treated at the Inselspital, Bern University Hospital (ISB), Switzerland with primary tumor location in the oral cavity, oropharynx, hypopharynx, and larynx. For these patients, additional information is provided including lateralization of the primary tumor, size and location of the largest metastases, and clinical involvement based on computed tomography (CT), magnetic resonance imaging (MRI), and/or 18FDG-positron emission tomography (PET/CT) imaging. Dataset 3 consists of 263 oropharyngeal SCC patients underlying a previous publication by Bauwens et al. [1], which were treated at CLB. For these patients, additional information including HPV status, lateralization of the primary tumor and clinically diagnosed lymph node involvement is provided. Reuse Potential: The data may be used to quantify the probability of occult lymph node metastases in each LNL, depending on an individual patient's characteristics of the primary tumor and the location of clinically diagnosed lymph node metastases. As such, the data may contribute to further personalize the elective treatment of the neck for HNSCC patients, i.e. definition of the elective clinical target volume (CTV-N) in radiotherapy (RT) and the extent of neck dissection (ND) in surgery. There exists only one similar publicly available dataset that reports clinical involvement per LNL in 287 oropharyngeal SCC patients [2]. The data presented in this article substantially extends the available data, it additionally includes pathologically assessed involvement per LNL, and it provides data for multiple subsites in the head and neck region.

The clinical acceptability of short versus long duration acquisitions for head and neck cancer using long-axial field-of-view PET/CT: a retrospective evaluation.

PURPOSE: To evaluate the utility of long duration (10 min) acquisitions compared to standard 4 min scans in the evaluation of head and neck cancer (HNC) using a long-axial field-of-view (LAFOV) system in 2-[18F]FDG PET/CT. METHODS: HNC patients undergoing LAFOV PET/CT were included retrospectively according to a predefined sample size calculation. For each acquisition, FDG avid lymph nodes (LN) which were highly probable or equivocal for malignancy were identified by two board certified nuclear medicine physicians in consensus. The aim of this study was to establish the clinical acceptability of short-duration (4 min, C40%) acquisitions compared to full-count (10 min, C100%) in terms of the detection of LN metastases in HNC. Secondary endpoints were the positive predictive value for LN status (PPV) and comparison of SUVmax at C40% and C100%. Histology reports or confirmatory imaging were the reference standard. RESULTS: A total of 1218 records were screened and target recruitment was met with n = 64 HNC patients undergoing LAFOV. Median age was 65 years (IQR: 59-73). At C40%, a total of 387 lesions were detected (highly probable LN n = 274 and equivocal n = 113. The total number of lesions detected at C100% acquisition was 439, of them 291 (66%) highly probable LN and 148 (34%) equivocal. Detection rate between the two acquisitions did not demonstrate any significant differences (Pearson's Chi-Square test, p = 0.792). Sensitivity, specificity, PPV, NPV and accuracy for C40% were 83%, 44%, 55%, 76% and 36%, whilst for C100% were 85%, 56%, 55%, 85% and 43%, respectively. The improved accuracy reached borderline significance (p = 0.057). At the ROC analysis, lower SUVmax was identified for C100% (3.5) compared to C40% (4.5). CONCLUSION: In terms of LN detection, C40% acquisitions showed no significant difference compared to the C100% acquisitions. There was some improvement for lesions detection at C100%, with a small increment in accuracy reaching borderline significance, suggestive that the higher sensitivity afforded by LAFOV might translate to improved clinical performance in some patients.

Superior loco-regional control after primary surgery compared to chemo-radiotherapy for advanced stage laryngeal cancer.

Objective: The optimal strategy to treat loco-regionally advanced squamous cell carcinoma of the larynx (LSCC) remains to be defined. The goal of this single institution retrospective study was to report on oncologic outcome of advanced LSCC treated with curative intent. Methods: Patients diagnosed and treated for stage T3-T4a LSCC between 2001 and 2014 were retrospectively analyzed. Time-to-event endpoints were calculated beginning from the date of histologic diagnosis, which were analyzed with log-rank test and Cox proportional hazard models. Results: The cohort was divided into two subgroups: primary radiotherapy with concomitant cisplatin (CRT) (n=30, 38%) and primary surgery (n=48, 62%). Median follow-up was 56 months. Locoregional control (LRC) for the primary surgery and CRT were 95% and 50% in 5 years, respectively (p<0.01). Progression free survival (PFS) for the primary surgery and CRT were 61% and 38% in 5 years, respectively (p=0.23). The overall survival (OS) after primary surgery and CRT in 5 years were 63% vs. 65%, respectively (p=0.93). The 5-years LRC was significantly superior after surgery compared to RT for cT3 primaries (100% vs 50%, p= 0.0022). No significant differences were observed in the remaining subgroups regarding cT stage and PFS or OS. Conclusion: Our series demonstrated superior LRC after primary surgery followed by risk-adapted adjuvant (C)RT compared to primary CRT in cT3 LSCC, but no significant difference in PFS or OS in locally-advanced LSCC. The optimal patient selection criteria for the ideal treatment for loco-regionally advanced LSCC still needs to be defined.

Free Tissue Transfer in Head and Neck Reconstruction: A Multidisciplinary 15-Year Experience.

BACKGROUND: Free tissue transfer is considered the gold standard in reconstruction of extensive defects in head and neck surgery. The aim of this 15-year retrospective study is to analyze the outcomes of free tissue transfers in the head and neck area in a tertiary referral university hospital. MATERIALS AND METHODS: A retrospective, single-center study of all patients undergoing free tissue transfers for head and neck reconstruction between 2006 and 2020 was performed. Patient demographics, comorbidities, flap characteristics, outcomes and complications were assessed. RESULTS: A total of 353 free flaps were performed. The most common defect etiology was synchronous oncologic resection (74.2%). The majority of patients had at least one comorbidity (70.3%), with smoking recorded in 46.2% of the cases and alcohol consumption in 31.7%. The anterolateral thigh flap was the most commonly used flap (37.7%), followed by the osteoseptocutaneous fibula flap (26.9%). Our overall flap success rate was 97.7%, while the overall complication rate was 45.9%. CONCLUSIONS: Free tissue transfer in head and neck reconstruction is reliable. However, complication rates remain high due to the complexity of such cases and frequent presence of comorbidities. Nonetheless, when effectively managed within a multidisciplinary team, complications rarely jeopardize the overall reconstruction outcome.

Head and neck cancer with synchronous nodules of the lung as a diagnostic and therapeutic challenge - A systematic review.

Head and neck squamous cell carcinoma (HNSCC) often presents with synchronous nodules of the lung (sNL), which may be benign nodules, second primary malignancies or metastases of HNSCC. We sought to gain an insight into the incidence of sNL and synchronous second primary of the lung (sSPML) in HNSCC patients and current opinions on useful diagnostic and therapeutic approaches. We conducted a systematic search of the PubMed database for articles that reported the simultaneous detection of HNSCC and sNL/sPML, within the timeframe of diagnosis and staging. Only studies involving humans were included, without restrictions for sex, age, ethnicity, or smoking history. All articles were categorised according to the Oxford Centre of Evidence-Based Medicine levels and their data collected. Data from 24 studies were analysed. Amongst HNSCC, the mean overall incidence rate of sNL and sSPML was 11.4% (range: 1.3-27%) and 2.95% (range: 0.4-7.4%), respectively. The possibility of a sNL to be a sSPML cannot be ignored (mean: 35.2%). Studies investigating smoking habits showed that the majority (98-100%) of HNSCC patients with sSPML were previous or active smokers. Detection of human papillomavirus through DNA analysis, p16 immunohistochemistry, and identification of clonal evolution were useful in differentiating metastasis from sSPML. 18FDG-PET scan was the most reliable method to diagnose sSPML (sensitivity: 95%; specificity: 96%; positive predictive value: 80%). With early sSPML detection and curative treatment, the 5-year overall survival rate is 34-47%. However, the proposed advantage of early detection warrants further evidence-based justification.

Sinonasal malignancies: histopathological entities, regional involvement and long-term outcome.

BACKGROUND: To assess a large patient cohort with sinonasal malignancies focusing on regional involvement, recurrence and oncological outcome. METHODS: Patients (n = 144) with malignant tumors of the nasal cavity and paranasal sinuses were treated at our tertiary referral center between 2008 and 2019. A chart review on patient and tumor characteristics, treatment and long-term outcome was performed. RESULTS: Most frequent histological types were squamous cell carcinoma (SCC) (n = 74), adenocarcinoma (n = 24) and mucosal melanoma (n = 18). Primary therapy was surgery in 66% of patients (n = 95) of which 65.8% (n = 66) received adjuvant radiotherapy. Twenty patients (13.8%) were initially staged as cN + and in seven cases, pN + status was histopathologically confirmed. Fifty-six of 130 patients (43.1%) had a relapse after curative intended therapy, including nine loco-regional (6.9%) and seven isolated regional recurrences (5.4%). Twelve of these 16 patients with (loco-)regional recurrence had SCC. Adenoid cystic carcinoma (87.5%) and SCC (65.3%) showed the best long-term overall survival. CONCLUSIONS: Regional involvement and regional recurrence are scarce. Because of rarity and heterogeneity, evidence on therapeutic management is sparse resulting in the lack of clinical guidelines.

Differentiated Papillary NUT Carcinoma: An Unexpected, Deceptively Bland Presentation of a Sinonasal Carcinoma.

BACKGROUND: In recent years, the list of tumor entities in the sinonasal tract has significantly expanded, requiring advanced diagnostic testing. We report the case of a 32-year-old patient with an unusual NUT carcinoma originating in the maxillary sinus, which showed extensive well-differentiated, papillary squamous morphology, similar to the spectrum of the recently described DEK::AFF2 fusion-associated carcinoma. METHODS: We performed immunohistochemical and molecular studies including EBV- and HPV-testing, as well as DNA/RNA next generation sequencing. RESULTS: The tumor showed predominantly exophytic papillary growth with mature squamous differentiation. An additional component harbored atypical, less differentiated basaloid tumor cells with infiltration of the adjacent stroma. Conspicuous inflammation was evident. There was no evidence of HPV DNA or EBV RNA. Next-generation sequencing revealed a NUT::NSD3 gene fusion corresponding to ("speckled-type") immunopositivity of NUT in the tumor cells. CONCLUSIONS: We describe a NUT::NSD3 gene fusion-associated NUT carcinoma of the sinonasal tract with a deceptively well-differentiated papillary growth pattern, thus expanding the morphological spectrum of this typically poorly differentiated neoplasm.

[Advanced nursing practice model for head and neck cancer: A practice development project]. / Advanced Nursing Practice für Patient_innen mit Kopf-Hals-Tumorerkrankungen und ihre Angehörigen.

Advanced nursing practice model for head and neck cancer: A practice development project Abstract. Background: Head and neck cancer confronts patients and their families with big challenges due to complex treatments as well as changes in vital functions and appearance. They require multifaceted support and benefit from coordinated, interprofessional collaboration and advanced nursing practice. Problem/aim: In a tertiary head and neck cancer center, a coordinating contact person was missing for patients, families and the care team. Therefore, a project was launched to develop an advanced nursing practice program. Methods: Methods included an advanced nursing practice concept, approaches for practice development, and action research. The project consisted of four phases: Stakeholder analysis and literature review were followed by the definition of the advanced nursing practice program, which was then tested during a pilot phase, and evaluated using structural/process data and stakeholder interviews. Results: Evidence-based, continuous, person-centered care was improved across the care continuum for patients/families. The nurses' expertise was supported and the collaboration with internal/external clinicians was facilitated. Patients/families valued the continuity offered by the advanced practice nurse. Discussion: The methodological approaches supported a goal-oriented approach; especially participatory practice development helped to address employees' concerns. Limitations/transfer: To date, a sustainable program cannot yet be warranted. For similar projects, an approach with stakeholder analysis, multidisciplinary focus, and early evaluation planning is recommended.

Risk Factors for Fear of Recurrence in Head and Neck Cancer Patients.

OBJECTIVE: Fear of recurrence (FoR) affects the quality of life of head and neck cancer survivors. Identification of factors predisposing to FoR may help to recognize and treat patients at risk. MATERIALS AND METHODS: For this exploratory study, 101 disease-free head and neck cancer survivors completed a cross-sectional survey in 2017 that included the FoR questionnaire at a random point in time during their follow-up. Additionally, the patients were asked to choose their favorite among four follow-up schedules with or without systematic imaging and varying frequency of visits. RESULTS: Elevated FoR was present in 36.6% of patients. Females and patients ≤65 years showed significantly higher FoR overall scores than males (score difference 3.40; CI 0.49-6.32; p = 0.022) and patients >65 years (score difference 4.25; CI 1.58-6.92; p = 0.002). A history of cancer recurrence or second primary malignancy increased the relative risk (RR) for elevated FoR (RR 1.7; CI 1.01-2.86; p = 0.046). Tumor stage and treatment modality were not significantly associated with elevated FoR or FoR overall score. Higher FoR overall scores were recorded in patients who favored intensive follow-up plans (mean overall FoR score 18 vs. 15; SD 7.7; p = 0.076) and systematic imaging in follow-up (17 vs. 13, SD 7.1; p = 0.034). CONCLUSION: Fear of recurrence in head and neck cancer patients is associated with female sex, younger age, and history of a past recurrence or second primary malignancy. Due to its high prevalence, it should be addressed in clinical practice and future research. LEVEL OF EVIDENCE: NA Laryngoscope, 133:1630-1637, 2023.

Prognostic and Predictive Biomarkers in Head and Neck Squamous Cell Carcinoma Treated with Radiotherapy-A Systematic Review.

Background: Radiotherapy is a mainstay in head and neck squamous cell carcinoma (HNSCC) treatment but is mostly applied without stratification by molecular diagnostics. Development of reliable biomarkers may have the potential to improve radiotherapy (RT) efficacy and reduce toxicity. We conducted a systematic review to summarize the field of biomarkers in HNSCC treated by RT. Methods: Pubmed and EMBASE were searched independently by two researchers following pre-defined inclusion and exclusion criteria. Z curves were generated to investigate publication bias. OncoKB was used for identification of druggable targets. Results: 134 manuscripts remained for data extraction. 12% of tumors were AJCC/UICC stage I-II and 82% were stage III-IV. The most common biomarkers were proteins (39%), DNA (14%) and mRNA (9%). Limiting analysis to prospective data and statistically significant results, we found three potentially druggable targets: ERCC2, PTCH1 and EGFR. Regarding data quality, AJCC/UICC stage was missing in 32% of manuscripts. 73% of studies were retrospective and only 7% were based on prospective randomized trials. Z-curves indicated the presence of publication bias. Conclusion: An abundance of potential biomarkers in HNSCC is available but data quality is limited by retrospective collection, lack of validation and publication bias. Improved study design and reporting quality might accelerate successful development of personalized treatments in HNSCC.

VoiceS: voice quality after transoral CO2 laser surgery versus single vocal cord irradiation for unilateral stage 0 and I glottic larynx cancer-a randomized phase III trial.

BACKGROUND: Surgery and radiotherapy are well-established standards of care for unilateral stage 0 and I early-stage glottic cancer (ESGC). Based on comparative studies and meta-analyses, functional and oncological outcomes after both treatment modalities are similar. Historically, radiotherapy (RT) has been performed by irradiation of the whole larynx. However, only the involved vocal cord is being treated with recently introduced hypofractionated concepts that result in 8 to 10-fold smaller target volumes. Retrospective data argues for an improvement in voice quality with non-inferior local control. Based on these findings, single vocal cord irradiation (SVCI) has been implemented as a routine approach in some institutions for ESGC in recent years. However, prospective data directly comparing SVCI with surgery is lacking. The aim of VoiceS is to fill this gap. METHODS: In this prospective randomized multi-center open-label phase III study with a superiority design, 34 patients with histopathologically confirmed, untreated, unilateral stage 0-I ESGC (unilateral cTis or cT1a) will be randomized to SVCI or transoral CO2-laser microsurgical cordectomy (TLM). Average difference in voice quality, measured by using the voice handicap index (VHI) will be modeled over four time points (6, 12, 18, and 24 months). Primary endpoint of this study will be the patient-reported subjective voice quality between 6 to 24 months after randomization. Secondary endpoints will include perceptual impression of the voice via roughness - breathiness - hoarseness (RBH) assessment at the above-mentioned time points. Additionally, quantitative characteristics of voice, loco-regional tumor control at 2 and 5 years, and treatment toxicity at 2 and 5 years based on CTCAE v.5.0 will be reported. DISCUSSION: To our knowledge, VoiceS is the first randomized phase III trial comparing SVCI with TLM. Results of this study may lead to improved decision-making in the treatment of ESGC. TRIAL REGISTRATION: ClinicalTrials.gov NCT04057209. Registered on 15 August 2019. Cantonal Ethics Committee KEK-BE 2019-01506.

Morbidity and Oncological Outcome After Curative Treatment in Sinonasal Squamous Cell Carcinoma.

OBJECTIVES: Sinonasal squamous cell carcinomas are rare and aggressive tumors. Curative therapy includes surgery and radiotherapy, with high risk for local morbidity and impaired quality of life. The objective of this study was to analyze a large cohort of patients with sinonasal squamous cell carcinoma on treatment morbidity and oncological outcome. METHODS: Patients with sinonasal squamous cell carcinoma (n = 75) treated at a tertiary referral center between 2008 and 2019 were identified. In patients with curative treatment intent (n = 70), a chart review and analysis on patient and tumor characteristics, morbidity, and oncological outcome was performed. RESULTS: Mean follow-up was 59 months. Primary curative therapy was surgery alone (n = 18), surgery with radiation (n = 25), and primary (chemo)radiation (n = 27). Forty-two (60%) patients suffered from treatment-related morbidity; most frequent symptoms were dry nasal mucosa (20%), nasal obstruction (14.3%), and vision impairment or loss (11.5%). Patients with early disease had less morbidity (51.4 vs 71.1%; P = 0.09), a lower recurrence rate (27% vs. 48.5%; P = 0.08), and better overall survival (92.5% vs. 71.1%; P = 0.01). CONCLUSION: Treatment-related morbidity is common after curative treatment of sinonasal squamous cell carcinomas. Early disease is beneficial in terms of occurrence and severity as multimodal treatment and recurrence can more likely be avoided.

Association of Multiprofessional Preoperative Assessment and Information for Patients With Head and Neck Cancer With Postoperative Outcomes.

IMPORTANCE: Multidisciplinary perioperative assessment for patients undergoing complex oncologic head and neck cancer (HNC) surgery is widely implemented. However, to our knowledge, the association of multiprofessional preoperative assessment, information, and briefing with postoperative outcomes has not been evaluated. OBJECTIVE: To compare postoperative complications, length of hospital stay (LOS), readmissions, mortality, and costs per case among patients undergoing complex oncologic HNC surgery before and after the implementation of a comprehensive preoperative multiprofessional assessment and information day (MUPAID). DESIGN, SETTING, AND PARTICIPANTS: This retrospective, single-center case-control study was conducted at a tertiary referral head and neck anticancer center/university cancer institute and compared patients with HNC who were undergoing complex oncological surgeries between January 2012 and July 2018 before (control group) and after (intervention group) implementation of the institutional MUPAID. Data analysis was conducted between 2019 and 2020. The intervention group comprised patients who participated in the MUPAID beginning in February 2015. These patients were assessed by a multiprofessional team and provided with structured and comprehensive information on the surgical procedure and its functional, social, financial, and psychological effects, as well as the postoperative care, rehabilitation, and follow-up period. Patients in the control group had also undergone complex oncologic HNC surgery and were selected through surgical procedure codes. MAIN OUTCOMES AND MEASURES: The end points were postoperative rate and severity of complications, LOS, readmissions, mortality, and costs per case. RESULTS: The study included 161 patients, 81 in the intervention (25 women [30.9%]) and 80 in the control group (18 women [22.5%]). The groups showed no relevant differences in sociodemographic, disease, and procedural characteristics. The intervention cohort presented with fewer major local and systemic complications (Clavien-Dindo score, III-V: 34.6% vs 52.5%; difference proportion, -0.179; 95% CI, -0.33 to -0.03), shorter median LOS (12 days [IQR, 10-16 days] vs 16 days [IQR, 11-20] days; effect size, 0.482; 95% CI Cohen d, 0.152-0.812) and decreased median charge per case ($50 848 [IQR, $42 510-$63 479] vs $69 602 [IQR, $45 631-$96 280]; effect size, 0.534; 95% CI Cohen d, 0.22-0.85). CONCLUSIONS AND RELEVANCE: The results of this case-control study suggest that MUPAID for patients who are undergoing complex oncologic HNC surgery is associated with shortened LOS and costs per case as well as decreased complications severity. These results are promising on a patient level in the potential to minimize individual treatment burden, as well as on an institutional and health care system level in the potential significant optimization of surgical outcomes and financial aspects.

Patterns of airway obstruction of non-acquired origin in children with and without major congenital anomalies.

Major congenital anomalies are known to play a role in the management and prognosis of airway obstruction. Most studies assess acquired forms of airway obstruction. Data on congenital or otherwise non-acquired forms of airway obstruction is sparse. In this retrospective, single-institution cohort study, we sought to evaluate and compare the patterns of airway obstruction in children with and without major congenital anomalies, and to assess the impact of management and outcome, irrespective of aetiology. Fifty-five patients were included, 23 with and 32 without underlying major congenital anomalies. Multilevel airway obstruction (usually affecting the nasopharynx, oropharynx, and the trachea) was more common in children with congenital anomalies (91% vs. 41%, p < .001). Consequently, these children required more frequent and earlier surgical management, especially tracheostomy and adenotonsillar surgery.Conclusions: Major congenital anomalies are associated with multilevel airway obstruction and poor functional prognosis. A simple clinical definition considering impact of major congenital anomalies on development and growth may help guide management plans following endoscopic evaluation of the entire airway and flanked by multidisciplinary discussions. What is Known: • Children with major comorbidities display increased disease severity and more prevalent multilevel airway obstruction • Previous studies include both children with acquired and non-acquired forms of airway obstruction; therefore, the actual impact major comorbidities in children with non-acquired causes of airway obstruction remain unclear. What is New: • A total of 42% children in this study population had major comorbidities with and impact on growth and/or psychomotor development, with a higher prevalence of multilevel airway obstruction and worse rates of functional improvement/recovery. • Children with major comorbidities require tracheostomy more often and earlier than those without major comorbidities, and remain tracheostomy-dependent for a longer time.

Proposed Prediction Model and Nomogram for Systemic Complications in Patients Undergoing Free Flap Head and Neck Reconstruction.

Postoperative complications in head and neck surgery are well-known, but a predictive model to guide clinicians in free flap reconstructions has not been established. This retrospective single-center observational study assessed 131 patients who underwent ablative surgery and received free flap reconstruction. Primary endpoint was the occurrence of systemic complications (PSC). Secondary endpoint was the generation of a nomogram of complications according to the CDC classification. In the ordinal regression model, postoperative administration of furosemide [1.36 (0.63-2.11), p < 0.0001], blood loss [0.001 (0.0004-0.0020), p = 0.004], postoperative nadir hemoglobin [-0.03 (-0.07-0.01), p = 0.108], smoking [0.72 (0.02-1.44), p = 0.043], and type of flap reconstruction [1.01 (0.21-1.84), p = 0.014] as predictors. A nomogram with acceptable discrimination was proposed (Somer's delta: 0.52). Application of this nomogram in clinical practice could help identify potentially modifiable risk factors and thus reduce the incidence of postoperative complications in patients undergoing microvascular reconstruction of the head and neck.

Impact of pretreatment second look 18FDG-PET/CT on stage and treatment changes in head and neck cancer.

BACKGROUND: Patients diagnosed with locoregionally advanced head and neck squamous cell carcinoma (LAHNSCC) regularly undergo staging with 18F-FDG PET/CT in our center. In cases of delays in radiotherapy (RT) planning CT more than 4 weeks after initial PET/CT or clinically suspected progress, PET/CT is repeated for restaging and as an RT planning reference. Our aim was to determine the impact of second-look PET/CT on stage migration, treatment change and RT planning. METHODS: Consequent treatment changes were categorized as minor and major. Minor changes were defined as PET/CT-based modifications of RT plans, e.g., the addition of anatomical compartments, changes in high- and low-risk dose levels or both. Major changes included changes from curative to palliative treatment intent and alterations of interdisciplinary treatment plans, such as the addition of induction chemotherapy, switch to primary surgery, no treatment and/or the necessity of additional diagnostic work-up resulting in the postponement or cancellation of treatment. RESULTS: Thirty-two newly diagnosed LAHNSCC patients who were treated between 2014 and 2018 underwent second-look PET/CT (median interval 42.5 days). Second-look PET/CT led to locoregional and distant upstaging in 3/32 and 1/32 patients, respectively. In 1/32 patients (3%), second-look PET/CT led to a palliative approach with systemic treatment. New lymph node metastases were discovered in 16 patients, 6 of whom also showed significant progression of the primary tumor, resulting in minor changes in 16 of the remaining 31 patients (52%) who were treated curatively. CONCLUSION: If RT treatment planning of LAHNSCC was delayed by more than 4 weeks after initial PET/CT staging or when progression was clinically suspected, a second look at 18FDG-PET/CT was performed. This led to changes in treatment planning in more than half of the cases, which is expected to directly influence oncologic outcomes.

Lymph Node Yield and Ratio in Selective and Modified Radical Neck Dissection in Head and Neck Cancer-Impact on Oncological Outcome.

Background: Lymph node metastases are associated with poor prognosis in head and neck squamous cell carcinoma (HNSCC). Neck dissection (ND) is often performed prior to or after (chemo)radiation (CRT) and is an integral part of HNSCC treatment strategies. The impact of CRT delivered prior to ND on lymph node yield (LNY) and lymph node ratio (LNR) has not been comprehensively investigated. Material and methods: A retrospective cohort study was conducted from January 2014 to 30 June 2019 at the University Hospital of Bern, Switzerland. We included 252 patients with primary HNSCC who underwent NDs either before or after CRT. LNY and LNR were compared in patients undergoing ND prior to or after CRT. A total of 137 and 115 patients underwent modified radical ND (levels I to V) and selective ND, respectively. The impact of several features on survival and disease control was assessed. Results: Of the included patients, 170 were male and 82 were females. There were 141 primaries from the oral cavity, 55 from the oropharynx, and 28 from the larynx. ND specimens showed a pN0 stage in 105 patients and pN+ in 147. LNY, but LNR was not significantly higher in patients undergoing upfront ND than in those after CRT (median: 38 vs. 22, p < 0.0001). Cox hazard ratio regression showed that an LNR ≥ 6.5% correlated with poor overall (HR 2.42, CI 1.12-4.89, p = 0.014) and disease-free survival (HR 3.416, CI 1.54-754, p = 0.003) in MRND. Conclusion: ND after CRT leads to significantly reduced LNY. An LNR ≥6.5% is an independent risk factor for decreased overall, disease-free, and distant metastasis-free survival for MRND.

The prognostic impact of daytime and seasonality of radiotherapy on head and neck cancer.

BACKGROUND: The potential impact of daytime and season of radiotherapy application on prognosis is unclear. This was analyzed in a retrospective cohort of patients who were diagnosed with non-metastatic head and neck squamous cell carcinoma (HNSCC) and treated with definitive radiotherapy with or without chemotherapy. MATERIALS AND METHODS: Patient and tumor characteristics, treatment parameters and outcome until last follow-up or death were obtained. Median radiotherapy delivery daytime of each patient was categorized as morning (AM) and afternoon (PM). Treatment season was defined by median date of treatment course. Each year was divided into DARK and LIGHT according to equinoxes. Time-to-event endpoints were defined by first biopsy confirming the HNSCC. RESULTS: Six hundred fifty-five cases were identified who were treated with (chemo)radiotherapy between 2002 and 2015. Median follow-up was 47 months. No significant heterogeneity in patient, tumor and treatment characteristics were observed between DARK and LIGHT or regarding median daily fraction time (X2 p > 0.05). Five-year loco-regional control (73% vs. 61%; p = 0.0108) and progression-free survival (51% vs. 43%; p = 0.0374) were superior when radiotherapy was administered in DARK. Neither the daytime nor any other treatment time-related parameter affected prognosis. CONCLUSION: This is the first study investigating and presenting the prognostic impact of seasonality regarding the treatment course on loco-regional control and progression-free survival (DARK > LIGHT). The biological mechanism of action is unclear. These results should be interpreted with caution and our findings have to be validated externally.

Granulocyte Colony-stimulating Factor Producing Oropharyngeal Squamous Cell Carcinoma.

CASE REPORT: We report on the case of a 47-year old woman with granulocyte colony-stimulating factor (G-CSF)-producing relapsed oropharyngeal squamous cell cancer. Palliative immunotherapy with nivolumab was started. Absolute neutrophilic count increased during the course of immunotherapy and correlated with tumour progression. Under chemotherapy with weekly paclitaxel, dramatic tumour regression and decreasing absolute neutrophilic count were noted. G-CSF concentration in serum increased from 4.77 to 9.61 pg/ml during the final phase of tumour progression. Immunohistochemical staining of the initial biopsies showed that some of the tumour cells as well as infiltrating cells stained positively for G-CSF, and some of the tumour cells even stained positively for the G-CSF receptor. CONCLUSION: Leukaemoid reaction in malignant disease with increased neutrophilic granulocytes has been shown to correlate with dismal prognosis in other tumours. The role of G-CSF in progression and prognosis of head and neck squamous cell carcinomas is still unclear but in patients with these tumours there seems also to be a correlation between elevated G-CSF and poor prognosis. Further systematic evaluation of G-CSF secretion in this tumour entity should clarify the role and potential treatment possibilities for these tumours.