Hypopharynx Cancer Research Articles

Claudin-1 in head and neck squamous cell carcinoma

Introduction. The objective response rate to immunotherapy is limited in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) patients, whose prognosis is still dismal. Few prognostic factors are clinically available, mostly related to patient or disease characteristics. Gene expression signatures offer better prognostic abilities but are mainly used in research. One such GE model classifies HNSCC into 6 clusters with different prognoses. Claudin-1 (CLDN1), which influences tumor microenvironment and immune cell infiltration, has emerged as a potential target, especially in cancers like HNSCC with high CLDN1 expression. Methods. A single-center cohort of 100 loco-regionally advanced HNSCC patients from the BD2Decide observational study was analyzed. Patients were selected to balance long-term survivors and deceased patients, including HPV-negative and HPV-positive cases. Primary tumor specimens underwent GE analysis using Affymetrix ClariomD chips. Primary endpoint was overall survival (OS). Results. The cohort comprised 100 HNSCC patients with a median age of 60 years, predominantly men (76%). Median OS and DFS were 94.24 and 42.79 months, respectively. CLDN1 expression varied significantly among primary sites, being highest in hypopharynx cancers. Differences in expression were not significant when stratified by HPV status or clinical stage. CLDN1 expression differed across the 6 transcriptomic clusters, with the highest levels in clusters associated with mesenchymal and hypoxic features. Higher CLDN1 expression correlated with shorter OS (HR 3, p=0.0023) and DFS (HR 2.14, p=0.02). Conclusion. CLDN1 expression is heterogeneous in HNSCC and carries prognostic significance. It is highest in tumors with HPV-like biology and hypoxic environments, and lowest in immune-sensitive clusters. High CLDN1 is a negative prognostic factor and a promising therapeutic target. Anti-CLDN1 treatments could improve outcomes of CLDN1+ HNSCC patients, and combination therapies with ICIs might overcome resistance in CLDN1- cases. These findings support the need for clinical studies on anti-CLDN1 therapies.

High Risk Human Papillomavirus Prevalence in Patients with Hypopharynx Cancer of Northeast India: A Pilot Study

Oncogenic viruses such as, Human papillomavirus (HPV) associated head and neck cancers have been considered to represent different etiological and pathological behaviour. This pilot study was conceived to investigate high risk HPV (hr-HPV) infection and its association with life style habits such as tobacco, alcohol consumption in patients with hypopharynx cancer from North –East India. A total of thirty four primary hypopharynx cancer biopsy specimens were collected. These samples were analysed for hr-HPV DNA using nested multiplex PCR (NMPCR). The lifestyle and dietary associated factors were collected through a self- designed questionnaire. The presence of hr-HPV was confirmed in 50% (n = 17) patients with hypopharynx cancer by nested multiplex PCR (NMPCR). Among hr-HPV positive cases, only HPV- 16 genotype was found. Significant association was observed between hr-HPV infections with alcohol consumption (p-0.025), alcohol with tobacco habit (p-0.01). Our study demonstrated that alcohol consumption, tobacco chewing may act as risk factors for hr-HPV infection in a subset of patients with hypopharynx cancer from the North-East region of India.

Time-to-Treatment Delays and Their Prognostic Implications in Pharyngeal Cancer-An Exploratory Analysis in Western Romania.

Diagnosis and treatment for pharyngeal cancer are decisive in determining prognosis. Diagnosis delays are frequent, representing a significant cause of avoidable mortality, and an important factor in subpar survival across the continuous HNC care delivery. The present study represents a retrospective analysis of medical records from Western Romania, which included 180 patients, to evaluate the impact of time-to-treatment delay on patients diagnosed with pharyngeal cancer. The data analyses were performed using the Kaplan-Meier method R (version 3.6.3) packages, including tidyverse, final-fit, mcgv, survival, stringdist, janitor, and Hmisc. The mean days from diagnosis until the end of treatment were higher for the nasopharynx group. Cox regression analysis regarding diagnosis to treatment duration categories showed an increased risk mortality by 3.11 times (95%CI: 1.51-6.41, p = 0.0021) with a Harrell's C-index of 0.638 (95%CI: 0.552-0.723). The hypopharynx and oropharynx locations increased risk mortality by 4.59 (95%CI: 1.55-13.55) and 5.49 times (95%CI: 1.79-16.81) compared to the nasopharynx location. The findings of this study led to the conclusion that it seems there is a trend of mortality risk for oropharynx and hypopharynx cancers due to delays in the time to treatment over 70 days, standing as a basis for further research as there is an imperative need for prospective multicenter studies.

Improved survival of locoregional-advanced larynx and hypopharynx cancer patients treated according to the DeLOS-II protocol.

Larynx organ preservation (LOP) in locoregional-advanced laryngeal and hypopharyngeal squamous cell carcinoma (LA-LHSCC) being only R0-resectable (clear margins > 5 mm) by total laryngectomy (TL) is desirable. Based on tumor-specific survival (TSS) and overall survival (OS) data from the RTOG 91-11 trial and meta-analyses of randomized clinical trials (RCTs), cisplatin-based concurrent radiochemotherapy (CRT) is discussed being superior to cisplatin-based induction chemotherapy followed by radiotherapy (IC+RT) and TL followed by postoperative RT (TL+PORT) or radiochemotherapy (TL+PORCT). Outside of RCTs, T4 LHSCC treated with TL+PORCT demonstrated improved OS and TSS compared to CRT alone; comparisons with docetaxel plus cisplatin (TP)-based IC+RT are unpublished. Head-to-head comparisons in RCTs of these four alternatives are missing. We utilized monocentric registry data to compare the outcome in the LOP trial DeLOS-II (NCT00508664) and propensity score (PS)-matched LHSCC patients. DeLOS-II utilized endoscopic tumor staging after one cycle of TP-based IC for selecting TL+R(C)T for non-responders versus IC+RT for responders. Main risk factors for survival (localization hypopharynx, T4, N+, tobacco smoking >30 pack years, alcohol consumption >60 g/day, age, sex) were used to calculate the individual PS for each DeLOS-II patient and 330 LHSCC patients suitable for DeLOS-II according to eligibility criteria in Leipzig by CRT (78), TL+PORT (148), and TL+PORCT (104). We performed PS matching with caliper width 0.2. The 52 DeLOS-II patients (whole intent-to-treat cohort) and three PS-matched cohorts (52 LHSCC patients each) had equal distribution regarding risk factors including Charlson comorbidity score (CS; all p > 0.05) but differed in outcome. During 12,498.6 months of follow-up, 162 deaths (36/41/43/42 in DeLOS-II/TL+PORCT/TL+PORT/CRT, p = 0.356) occurred; DeLOS-II patients had superior OS and TSS. Compared to DeLOS-II, the HR (95% CI) observed in TL+PORCT, TL+PORT, and CRT for OS and TSS were 1.49 (0.92-2.43), 1.49 (1.15-3.18), and 1.81 (1.11-2.96) for OS; and 2.07 (0.944-4.58), 3.02 (1.32-6.89), and 3.40 (1.58-7.31) for TSS. In addition potential LOP, LA-LHSCC suitable for LOP according the DeLOS-II protocol may achieve improved survival.

Beyond the initial diagnosis: Epidemiological factors associated with second primary cancers among patients with head and neck squamous cell carcinoma (a SEER-based study).

6081 Background: Patients with Head and Neck cancer squamous cell carcinoma (HNSSC) have an increased risk of developing a Second Primary Cancer (SPC). We evaluated the epidemiological factors associated with SPC among patients with Stage 1-4 HNSCC using the SEER database from 2004-2020. Methods: Stage 1-4 HNSSC cases from 2004-2020, with a minimum of six months of follow-up, were identified using SEER.Stat 8.4.2 using ICD-10 CM codes. Adjusted odd’s ratios (aOR) for developing SPC (dependent variable) and the independent variables (sex, age, race and ethnicity, site of primary cancer, and marital status) were generated using multivariate logistic regression. All the analyses were performed on SAS OnDemand. Results: 127,919 cases of HNSCC were identified from 2004-2020. Oral cavity cancer accounted for 41.2% of the cases. 18,192 (14.2%) patients developed SPC. Patients with primary hypopharynx, laryngeal, and oral cavity cancer had the highest odds of developing SPC (p< 0.0001). The most prevalent sites for developing SPC were the lung (25.0%), head and neck (24.1%), and prostate (10.6 %). Males had significantly higher odds of developing SPC than females (aOR - 1.11 (1.07, 1.5)). When compared to the NH-white population, Hispanics and NH-Asian had significantly lower odds of developing SPC (aOR - 0.72 (0.68, 0.77) and 0.72 (0.68, 0.78) respectively), while NH-Blacks had higher odds of developing SPC (aOR - 1.1(1.01,1.23)). Conclusions: Our study emphasizes the substantial risk of SPC in HNSCC patients, with oral cavity cancer as the predominant primary cancer subtype. Specific HNSCC sites show elevated SPC odds, mainly primary hypopharyngeal cancer, emphasizing the need for targeted surveillance. Demographic variations reveal gender and racial disparities in SPC susceptibility, advocating for tailored monitoring and preventive strategies in high-risk subpopulations to enhance overall cancer care and survivorship. [Table: see text]

Polygenic Risk Score in Predicting Esophageal, Oropharyngeal, and Hypopharynx Cancer Risk among Taiwanese Population.

Esophageal cancer shares strong associations with oropharyngeal and hypopharyngeal cancers, primarily due to shared risk factors like excessive tobacco and alcohol use. This retrospective study at Taichung Veterans General Hospital involved 54,692 participants, including 385 with squamous cell carcinoma (SCC) of the esophagus, oropharynx, or hypopharynx. Using a polygenic risk score (PRS) derived from 8353 single-nucleotide polymorphisms, researchers aimed to assess its correlation with cancer incidence and prognosis. The study found a 1.83-fold higher risk of esophageal, oropharyngeal, and hypopharyngeal SCCs in participants with a high PRS (Q4) compared to the low-PRS group (Q1). Esophageal cancer risk demonstrated a significant positive association with the PRS, as did hypopharyngeal cancer. Clinical parameters and staging showed limited associations with PRS quartiles, and the PRS did not significantly impact recurrence or mortality rates. The research highlighted that a higher PRS is linked to increased susceptibility to esophageal and hypopharyngeal cancer. Notably, a specific polygenic risk score, PGS001087, exhibited a discernible association with SCC risk, particularly in specific subtypes and advanced disease stages. However, it was not significantly linked to clinical cancer staging, emphasizing the multifactorial nature of cancer development. This hospital study reveals that a higher PRS correlates with increased susceptibility to esophageal and hypopharyngeal cancers. Notably, PGS001087 shows a discernible association with SCC risk in specific subtypes and advanced stages, although not significantly linked to clinical cancer staging. These findings enhance our understanding of genetic factors in upper aerodigestive tract cancers, particularly esophageal SCC, guiding future research and risk assessment strategies.

Identifying Lymph Nodes and Their Statuses from Pretreatment Computer Tomography Images of Patients with Head and Neck Cancer Using a Clinical-Data-Driven Deep Learning Algorithm.

Head and neck cancer is highly prevalent in Taiwan. Its treatment mainly relies on clinical staging, usually diagnosed from images. A major part of the diagnosis is whether lymph nodes are involved in the tumor. We present an algorithm for analyzing clinical images that integrates a deep learning model with image processing and attempt to analyze the features it uses to classify lymph nodes. We retrospectively collected pretreatment computed tomography images and surgery pathological reports for 271 patients diagnosed with, and subsequently treated for, naïve oral cavity, oropharynx, hypopharynx, and larynx cancer between 2008 and 2018. We chose a 3D UNet model trained for semantic segmentation, which was evaluated for inference in a test dataset of 29 patients. We annotated 2527 lymph nodes. The detection rate of all lymph nodes was 80%, and Dice score was 0.71. The model has a better detection rate at larger lymph nodes. For those identified lymph nodes, we found a trend where the shorter the short axis, the more negative the lymph nodes. This is consistent with clinical observations. The model showed a convincible lymph node detection on clinical images. We will evaluate and further improve the model in collaboration with clinical physicians.

Hypopharynx Cancer Incidence in Kazakhstan: 2017-2021.

The article studies the geographical features of the incidence of hypopharynx cancer (HPC) in Kazakhstan. The retrospective study was done for the period 2017-2021. Descriptive and analytical methods of ecoepidemiology were used. Crude (CR), age-specific (ASIR), age-standardized (ASR), equalized incidence rates and approximation were calculated. The dynamics of indicators was investigated using component analysis according to methodological recommendations. The method of drawing up a cartogram based on the determination of the standard deviation (σ) from the mean (x) was applied. During the study period, 814 new cases of HPC were registered. The incidence rate decreased from 0.898 (2017) to 0.895 in 2021 and the overall decline was 0.003 per 100,000 population, including due to the age structure - ∑ΔA=+0.04, due to the risk of acquiring illness - ∑ΔR=-0.05 and their combined effect - ∑ΔRA=+0.01. The component analysis revealed that the increase in the number of patients with HPC was mainly due to the growth of the population (ΔP=+37.0%), changes in its age structure (ΔA=+106.1%) and changes associated with the risk of acquiring illness (ΔR=-133.4%). The cartograms were allocated according to the following criteria: low - up to 0.730/0000, average - from 0.73 to 1.180/0000, high - above 1.180/0000. The results of the spatial assessment showed the highest levels of HPC incidence in following regions: Atyrau (1.960/0000) and West Kazakhstan (1.580/0000). Thus, this is the first epidemiological study of HPC, which assessed the role of the influence of various factors, including demographic and risk of acquiring illness, on the dynamics of incidence, taking into account gender differences and geographical variability.

Real-world data of immunotherapy from China in recurrent or metastatic head and neck squamous cell carcinoma

PurposeImmune checkpoint inhibitors (ICIs) have become a standard therapy for recurrent or metastatic head and neck squamous cell carcinoma (R/MHNSCC), however, there are still unanswered questions about immunotherapy. Furthermore, immunotherapy for R/MHNSCC of the mainland Chinese population are lacking. The aim of this study is to evaluate the efficacy and safety of ICIs in real-world settings in China. Materials and methodsWe retrospectively reviewed 59 patients with R/MHNSCC who received immunotherapy between May 2019 and December 2021. We assessed demographics, efficacy, survival and safety. ResultsFifty-nine patients were included in the study, all of whom had R/MHNSCC affecting the oral cavity, oropharynx, hypopharynx, larynx, nasal cavity, paranasal sinuses and metastatic cancer in the neck with an unknown primary. The objective response rate (ORR) for all patients was found to be 40.6 %. Out of these patients, 11 patients achieved a complete response and 13 achieved a partial response. The median progression-free survival (PFS) was calculated to be 10.64 months (range: 1.15–29.24 months), while the median overall survival (OS) was 21.75 months (range 2.0–37.55 months). The addition of local radiotherapy resulted in higher ORR and PFS compared to previous reports. Notably, patients with R/MHNSCC in the paranasal sinuses and nasal cavity also showed benefits from immunotherapy. Additionally, patients who achieved stable disease (SD) had similar survival rates to those who achieved partial response (PR), indicating that SD is also an indicator of clinical benefit from immunotherapy. The overall incidence of immune-related adverse reactions in this study was low, with fatigue and rash being the most common side effects. ConclusionThese findings highlight the effectiveness and safety of immunotherapy for R/MHNSCC in a real-world setting in China. Further investigation is warranted to explore the potential benefits of incorporating local radiotherapy into the treatment of R/MHNSCC.

New cycloartane triterpenoids from Dysoxylum malabaricum and their cytotoxic evaluation

The cytotoxic dichloromethane-methanol bark extract of Dysoxylum malabaricum was subjected to bioassay-guided fractionation, followed by systematic dereplication to focus on the identification of new compounds. From the bark of Dysoxylum malabaricum, two new cycloartane-type triterpenoids were isolated in addition to two previously known triterpenoids. The structures and absolute configurations of the isolated compounds were elucidated unambiguously via NMR, HRESIMS data, and electronic circular dichroism calculations. The isolated compounds were tested for their cytotoxic potential against the panel of breast, lung, and hypopharynx cancer cell lines and displayed notable cytotoxicity against breast cancer cell lines. Compound 3 exhibited the most potent cytotoxic effect with an IC50 14 µM against MCF-7 cell lines and induced cell cycle arrest. Through western blot and cell cycle analysis, it was revealed that compound 3 halts the G0/G1 phase of the cell cycle by inhibiting CDC20 and CDC25 enzymes.

Conventional radiation therapy with hyperfractionated radiation therapy in cancer hypopharynx - A prospective comparative study

Cancer treatment of the head and neck, the effectiveness of hyperfractionated radiation therapy (HFRT) has been revealed in recent randomized trials, mainly in their local control. As the hypopharynx is situated near the larynx, to achieve greater laryngeal preservation, local control of hypopharyngeal cancers should be achieved; it is very important to enhance the patient’s quality of life. In this study, hyperfractionated radiation therapy results were compared with conventional radiation therapy (CFRT) results.Patients with squamous cell cancer of hypopharynx (Stage II to IVA); were submitted with hyperfractionated (n = 34) or conventionally fractionated (n = 22) radiotherapy, with chemotherapy, between July 2018 to January 2020.In conventional radiotherapy, each patient received 2 Gy per fraction with a total dose of 66 Gy at over 6.3 weeks, along with concurrent cisplatin (30 mg/m 2) weekly. In hyperfractionated radiotherapy, each patient received 1.2 Gy per fraction two fractions per day six hours apart with a total dose of 72 Gy at over 6 weeks, along with concurrent cisplatin (30 mg/m 2) weekly. The endpoints were tumor response and toxicities.: Complete response rate in the HFRT group was 85.29% and that in the CFRT group was 68.18%. The most prevalent acute toxicities were skin, mucosal and dysphagia related. The acute skin toxicity was significantly higher in CFRT (54.55%) than in HFRT (44.12%).: This study suggests that for the treatment of locally advanced hypopharynx cancers, hyperfractionated radiation therapy with simultaneous chemotherapy can be a standard method of treatment and care.

Combinations of PRI-724 Wnt/β-Catenin Pathway Inhibitor with Vismodegib, Erlotinib, or HS-173 Synergistically Inhibit Head and Neck Squamous Cancer Cells.

The Wnt/β-catenin, EGFR, and PI3K pathways frequently undergo upregulation in head and neck squamous carcinoma (HNSCC) cells. Moreover, the Wnt/β-catenin pathway together with Hedgehog (Hh) signaling regulate the activity of cancer stem cells (CSCs). The aim of this study was to investigate the effects of the combinatorial use of the Wnt/β-catenin and Hh pathway inhibitors on viability, cell cycle progression, apoptosis induction, cell migration, and expression of CSC markers in tongue (CAL 27) and hypopharynx (FaDu) cancer cells. Co-inhibition of Wnt signaling with EGFR or PI3K pathways was additionally tested. The cells were treated with selective inhibitors of signaling pathways: Wnt/β-catenin (PRI-724), Hh (vismodegib), EGFR (erlotinib), and PI3K (HS-173). Cell viability was evaluated by the resazurin assay. Cell cycle progression and apoptosis induction were tested by flow cytometric analysis after staining with propidium iodide and Annexin V, respectively. Cell migration was detected by the scratch assay and CSC marker expression by the R-T PCR method. Mixtures of PRI-724 and vismodegib affected cell cycle distribution, greatly reduced cell migration, and downregulated the transcript level of CSC markers, especially POU5F1 encoding OCT4. Combinations of PRI-724 with erlotinib or HS-173 were more potent in inducing apoptosis.

Treatment patterns of targeted and nontargeted therapies and survival effects in patients with locally advanced head and neck cancer in Taiwan

BackgroundTaiwan’s National Health Insurance has covered targeted therapy, namely cetuximab, for locally advanced head and neck cancers (LAHNC) since July 2009. This study examines treatment trends and survival effects of locally advanced head and neck cancer patients before and after Taiwan’s National Health Insurance covered cetuximab.MethodsWe examined treatment trends and survival effects for patients with LAHNC using Taiwan’s National Health Insurance Research Database. Patients who received treatment within 6 months were categorized as either nontargeted or targeted therapy groups. We analyzed treatment trends with the Cochran-Armitage trend test and explored factors associated with treatment selection and survival effects using multivariable logistic regression and Cox proportional hazards models.ResultsOf the 20,900 LAHNC patients included in the study, 19,696 received nontargeted therapy, while 1,204 received targeted therapy. Older patients with more comorbid conditions, advanced stages and patients with hypopharynx and oropharynx cancers were more likely to receive targeted therapy with concomitant cetuximab treatment. Patients who received targeted therapy in addition to other treatment modalities had a greater risk of one-year and long-term all-cause mortality or cancer-specific mortality than those without receiving targeted therapy (P < 0.001).ConclusionsOur study found an increasing trend in cetuximab utilization among LAHNC after reimbursement in Taiwan, but overall usage rates were low. LAHNC patients receiving cetuximab with other treatments had higher mortality risk than those receiving cisplatin, suggesting cisplatin may be preferred. Further research is needed to identify subgroups that could benefit from concomitant cetuximab treatment.

The comparison of manual and mechanical anastomosis after total pharyngolaryngoesophagectomy.

Total pharyngolaryngoesophagectomy (TPLE) is considered as a curative treatment for hypopharynx cancer and cervical esophageal carcinomas (HPCECs). Traditional pharyngo-gastric anastomosis is usually performed manually, and postoperative complications are common. The aim of this study was to introduce a new technique for mechanical anastomosis and to evaluate perioperative outcomes and prognosis. From May 1995 to Nov 2021, a series of 75 consecutive patients who received TPLE for a pathological diagnosis of HPCECs at Sun Yat-sen Memorial Hospital were evaluated. Mechanical anastomosis was performed in 28 cases and manual anastomosis was performed in 47 cases. The data from these patients were retrospectively analyzed. The mean age was 57.6 years, and 20% of the patients were female. The rate of anastomotic fistula and wound infection in the mechanical group were significantly lower than that in the manual group. The operation time, intraoperative blood loss and postoperative hospital stays were significantly higher in the manual group than that in the mechanical group. The R0 resection rate and the tumor characteristics were not significantly different between groups. There was no significant difference in overall survival and disease-free survival between the two groups. The mechanical anastomosis technology adopted by this study was shown to be a safer and more effective procedure with similar survival comparable to that of manual anastomosis for the HPCECs patients.

Association of Surgical Margin Distance With Survival in Patients With Resected Head and Neck Squamous Cell Carcinoma

Clear surgical margins reduce the risk of local recurrence, improve survival, and determine decision-making with regard to adjuvant treatment of squamous cell carcinoma of the head and neck (SCCHN). However, the definitions of clear, close, or positive surgical margins vary in both the literature and in practice. To examine whether the association between surgical margin distance and survival varies by primary tumor site. This was a secondary analysis of a multi-institutional, multinational randomized clinical trial. The trial enrolled patients from January 22, 2007, to March 29, 2013, with stage II to IVA resected SCCHN with extranodal extension (ENE) or positive margins (<5 mm from invasive tumor to the resected margin). The current analysis included those patients with known ENE and margin status and was conducted from April 29, 2022, to December 19, 2022. Patients received adjuvant chemoradiotherapy plus either placebo or lapatinib. Overall survival (OS) was calculated to examine association with surgical margin distance, primary site, and survival, with stratification by ENE status. Among 688 patients enrolled in the trial, 630 patients with known ENE and margin status were included. Exact patient ages were not made available; 523 (83%) patients were male, and 415 (66%) patients were White. Patients with 1 high-risk feature (positive margins or ENE) had significantly better OS vs 2 high-risk features (hazard ratio [HR], 0.65; 95% CI, 0.49-0.87), although most other results were not statistically significant. For example, in the cohort with ENE-negative disease, multivariable adjusted analysis showed nonsignificant improvements with shorter surgical margin distance (1- to 5-mm margins), and no association with OS was found in the cohort with ENE-positive status (either >5 mm margins or 1-5 mm margins). The association between survival and margin distance varied based on primary site, human papillomavirus (HPV) status, and ENE status. For example, HPV-positive status was associated with a significant and clinically meaningful increase in survival (adjusted HR, 0.33; 95% CI, 0.11-0.97). The improvement was greatest, although not significantly so, in patients with ENE- and HPV-negative oropharynx (OP), hypopharynx (HP), and larynx cancer (HR, 0.57; 95% CI, 0.30-1.10). No survival benefit was seen in ENE-negative oral cavity cancer (HR, 0.89; 95% CI, 0.45-1.77), nor was an association observed between margins and OS in HPV-positive OP cancer. In this secondary analysis of a randomized clinical trial, the presence of high-risk features (extranodal extension, positive margins, or both) was associated with worse survival; longer survival was observed with greater surgical margin distance among patients with oral cavity tumors and human papillomavirus-negative tumors of the OP, larynx, or HP. No other significant differences were found. These findings support variable interpretation of surgical margin distance based on the primary site and HPV status. ClinicalTrials.gov Identifier: NCT00424255.

Is locally advanced head and neck cancer ‘increasing’ in the Netherlands? The paradox of absolute numbers, standardized incidence rates and proportional share

BackgroundSeveral reports have indicated that locally advanced head and neck cancer (LAHNC) has increased in the past decade. However, incidence trends cannot be easily compared because slightly different definitions of LAHNC were used. AimTo investigate if the incidence of locally advanced disease (LAD) in the oral cavity, oropharynx, hypopharynx and larynx is indeed increasing over time, considering the growing and ageing population in the Netherlands. Patients and methodsData were obtained from the Netherlands Cancer Registry (NCR). Primary head and neck squamous cell carcinomas of the oral cavity, oropharynx, hypopharynx and larynx diagnosed between 1989 and 2017 were included. Yearly numbers and European standardized incidence rates (ESRs) were reported by extent of disease. The annual percentage change (APC) over time in ESRs was calculated to assess trends. ResultsAbsolute numbers and ESRs of LAD increased over time for oral cavity and most prominently for oropharynx carcinomas (before 1996, APC: 0.4, 95%CI: 0.1; 0.8 and APC: 5.7 (95%CI: 3.1; 8.4) after 1996: 1.5 (1.0; 2.0) respectively. For hypopharynx cancer the absolute number and ESR of LAD increased until 1997 and declined with 0.8% per year since 1997. Absolute numbers of patients with larynx cancer stayed stable over time, while ESR decreased (APC: −0.8 (95%CI: −1.1; −0.6)). ConclusionThe perception of an increasing trend in LAD in the Netherlands can be attributed to the increasing incidence of oral cavity and oropharynx carcinomas. For LAD of the hypopharynx a decreasing trend was observed. In larynx cancer, the proportional share of LAD of the larynx increased, even though incidence rates declined.

Imaging Recommendations for Diagnosis, Staging and Management of Larynx and Hypopharynx Cancer

AbstractWe discussed the imaging recommendations for diagnosis, staging, and management of larynx and hypopharynx cancer. Carcinoma of the larynx is a common cancer, with males being affected more. Hypopharyngeal carcinoma is less common than laryngeal malignancies. Squamous cell carcinoma is the most common histological type. Nonsquamous cell malignant lesions are rare and mostly submucosal lesions. Clinical examination and endoscopy play an integral role in its detection and staging. Imaging also plays a major role in its staging, including local disease extent, nodal and distant metastatic status, as well as to assess response to therapy. Follow-up of treated cases and differentiation of recurrence from post treatment changes can be done on imaging. Early stage disease is treated with single modalities such as radiotherapy or surgery. Advanced disease is treated with multimodality of either chemoradiotherapy or surgery followed by adjuvant radiotherapy with or without concurrent chemotherapy.

Prognosticating Gross Tumor Volume in Head-and-Neck Cancer - Redefining Gross Tumor Volume Beyond Contouring.

Precision radiotherapy (RT) requires accurate delineation of gross tumor volumes (GTVs) for targeted dose delivery. Volumetric measurement of this GTV can predict the treatment outcomes. This volume has been limited for mere contouring and its potential as the prognostic factor is less explored. The data of 150 patients with oropharynx, hypopharynx, and larynx cancer undergoing curative intensity-modulated RT and weekly cisplatin between April 2015 and December 2019 were retrospectively evaluated. GTV-P (primary), GTV-N (nodal), and GTV-P+N were defined, and volumetric parameters were generated. Volume thresholds were defined as per the receiver operating characteristics, and the prognostic value of these tumor volumes (TVs) with respect to treatment outcomes was analyzed. All patients completed 70 Gy, median chemotherapy cycles were six. Mean GTV-P, GTV-N, and GTV-P+N were 44.5 cc, 13.4 cc, and 57.9 cc, respectively. Oropharynx constituted 45% of cases. Forty-nine percent had Stage III disease. Sixty-six percent had complete response (CR). As per the defined cutoff values, GTV-P <30cc, GTV-N <4 cc, and GTV-P+N <50 cc had better CR rates with P < 0.05 (82.6% vs. 51.9%; 74% vs. 58.4% and 81.5% vs. 47.8%, respectively). At median follow-up of 21.4 months, overall survival (OS) was 60% and median OS was 32.3 months. The median OS in patients with GTV-P <30 cc, GTV-N <4 cc, and GTV-P+N <50 cc was better with P < 0.05 (59.2 vs. 21.4; 59.2 vs. 22.2, and 59.2 vs. 19.8 months, respectively). GTV should not just be limited for contouring but its role as an important prognostic factor has to be recognized.

Patterns of failure for hypopharynx cancer patients treated with limited high-dose radiotherapy treatment volumes.

Optimal radiotherapy treatment volumes for patients with locally advanced hypopharynx squamous cell carcinoma should ensure maximal tumor coverage with minimal inclusion of normal surrounding structures. Here we evaluated the effectiveness of a direct 3-mm high-dose gross tumor volume to planning target volume expansion on clinical outcomes for hypopharynx cancers. We performed a retrospective analysis of patients with hypopharynx carcinoma treated between 2004 and 2018 with primary radiotherapy using a direct high-dose gross tumor volume to planning target volume expansion and with or without concurrent systemic therapy. Diagnostic imaging of recurrences was co-registered with the planning CT. Spatial and volumetric analyses of contoured recurrences were compared with planned isodose lines. Failures were initially defined as in field, marginal, elective nodal, and out of field. Each failure was further classified as central high-dose, peripheral high-dose, central intermediate/low-dose, peripheral intermediate/low-dose, and extraneous. Clinical outcomes were analyzed by Kaplan-Meier estimation. Thirty-six patients were identified. At a median follow-up at 52.4 months, estimated 5-year overall survival was 59.3% (95% confidence interval [CI], 36.3%-74.1%), 5-year local and nodal control was 71.7% (95% CI, 47.1%-86.3%) and 69.9% (95% CI, 57.0%-82.6%), respectively. The most common failure was in the high-dose primary target volume. The gastrostomy tube retention rate at 1 year among patients without recurrence was 13.0% (95% CI, 3.2%-29.7%). Minimal high-dose target volume expansions for hypopharynx cancers were associated with favorable locoregional control. This approach may enable therapy intensification to improve clinical outcomes.

Oncologic Outcomes After Clinically Node-Negative Salvage Laryngectomy

Controversy exists regarding management of the clinically node-negative neck in patients with recurrent larynx or hypopharynx cancers who received total laryngectomy after definitive radiation with or without chemotherapy. To explore clinical and oncologic outcomes after elective neck dissection vs observation in patients who received clinically node-negative salvage total laryngectomy. This cohort study was performed from January 2009 to June 2021 at a single, high-volume tertiary care center. Follow-up was conducted through June 2021 for all patients. Survival outcomes were based on at least 2 years of follow-up. Patients aged 18 years or older with recurrent, clinically node-negative larynx or hypopharynx tumors after definitive nonsurgical treatment who were treated with a salvage total laryngectomy were included. Data were analyzed from October 2021 through September 2022. Elective neck dissection. Presence and location of occult nodal metastasis in electively dissected necks, along with differences in fistula rates and overall and disease-free survival between patients receiving elective neck dissection vs observation. Among 107 patients receiving clinically node-negative salvage total laryngectomy (median [IQR] age, 65.0 [57.8-71.3] years; 91 [85.0%] men), 81 patients underwent elective neck dissection (75.7%) and 26 patients underwent observation (24.3%). Among patients with elective neck dissection, 13 patients had occult nodal positivity (16.0%). Recurrent supraglottic (4 of 20 patients [20.0%]) or advanced T classification (ie, T3-T4; 12 of 61 patients [19.7%]) had an occult nodal positivity rate of 20% or more, and positive nodes were most likely to occur in levels II and III (II: 6 of 67 patients [9.0%]; III: 6 of 65 patients [9.2%]; VI: 3 of 44 patients [6.8%]; IV: 3 of 62 patients [4.8%]; V: 0 of 4 patients; I: 0 of 18 patients). There was a large difference in fistula rate between elective neck dissection (12 patients [14.8%]) and observed (8 patients [30.8%]) groups (difference, 16.0 percentage points; 95% CI, -3.4 to 35.3 percentage points), while the difference in fistula rate was negligible between 50 patients undergoing regional or free flap reconstruction (10 patients [20.0%]) vs 57 patients undergoing primary closure (10 patients [17.5%]) (difference, 2.5 percentage points; 95% CI, -12.4 to 17.3 percentage points). Undergoing elective neck dissection was not associated with a clinically meaningful improvement in overall or disease-free survival compared with observation. Recurrent hypopharynx subsite was associated with an increased risk of death (hazard ratio, 4.28; 95% CI, 1.81 to 10.09) and distant recurrence (hazard ratio, 7.94; 95% CI, 2.07 to 30.48) compared with glottic subsite. In this cohort study, patients with recurrent supraglottic or advanced T classification tumors had an increased occult nodal positivity rate, elective neck dissection was not associated with survival, and patients with recurrent hypopharynx subsite were more likely to have a distant recurrence and die of their disease. These findings suggest that underlying disease pathology rather than surgical management may be associated with survival outcomes in this population.