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JAMA Otolaryngology-- Head & Neck... Jun 2024Patients with unknown primary squamous cell carcinoma (CUP) with cervical metastases typically receive comprehensive radiotherapy (RT) of the pharynx and bilateral neck....
IMPORTANCE
Patients with unknown primary squamous cell carcinoma (CUP) with cervical metastases typically receive comprehensive radiotherapy (RT) of the pharynx and bilateral neck. Typically, these patients receive comprehensive RT of the pharynx and bilateral neck that may produce treatment-related toxic effects.
OBJECTIVE
To determine whether localization of occult oropharyngeal cancers with transoral robotic surgery (TORS) combined with reduced pharyngeal and neck RT volumes provides acceptable disease control.
DESIGN, SETTING, AND PARTICIPANTS
This phase 2, single-group nonrandomized controlled trial at a single institution accrued 32 prospective participants with p16-positive CUP without a primary squamous cell carcinoma on examination and imaging from 2017 to 2019, and 24-month follow-up. The data analysis was conducted from January 2021 to June 2022.
INTERVENTION
Diagnostic- (n = 13) or therapeutic-intent (n = 9) TORS, with pharyngeal-sparing radiotherapy (PSRT) prescribed for negative margins or pT0, and unilateral neck RT (UNRT) prescribed for unilateral lymphadenopathy with lateralized primary tumor or pT0.
MAIN OUTCOMES AND MEASURES
Out-of-radiation treatment volume failure (<15% was hypothesized to be acceptable) and reports of local and regional recurrence, overall survival, toxic effects, swallowing outcomes (per the MD Anderson Dysphagia Inventory), and videofluoroscopic swallow (per Dynamic Imaging Grade of Swallowing Toxic Effects [DIGEST]) ratings.
RESULTS
The study sample comprised 22 patients (mean [SD] age, 59.1 [5.7] years; 3 [14%] females and 19 [86%] male) with CUP. Of these, 19 patients (86%) had tumor stage cN1; 2 (9%), cN2; and 1 (5%), cN3. Five patients (23%), 14 patients (64%), and 3 patients (13%) had 0, 1, or 2 primary tumors, respectively. Twenty patients received RT; of these, 9 patients (45%) underwent PSRT and 10 patients (50%), UNRT. In the diagnostic-intent group, 8 patients (62%) and 5 patients (38%) underwent RT and RT-concurrent chemotherapy, respectively. In the therapeutic-intent group, 6 patients (67%) and 1 patient (11%) received adjuvant RT-concurrent chemotherapy, respectively; 2 patients declined RT. Two-year out-of-radiation treatment volume failure, locoregional control, distant metastasis control, and overall survival were 0%, 100%, 95%, and 100%, respectively. Grade 3 or 4 surgical, acute, and late toxic effects occurred in 2 (9%), 5 (23%), and 1 (5%) patients, respectively. PSRT was associated with lower RT dose to superior constrictors (37 vs 53 Gy; mean difference, 16 Gy; 95% CI, 6.4, 24.9), smaller decline in swallowing scores during treatment (19.3 vs 39.7; mean difference, -20.4; 95% CI, -34.1 to -6.1), and fewer patients with worsening DIGEST grade on findings of videofluoroscopic swallow studies at 2 years (0% vs 60%; difference, 60%; 95% CI, 30% to 90%).
CONCLUSIONS AND RELEVANCE
These findings indicate that TORS for p16-positive CUP allows RT volume deintensification with excellent outcomes and support future investigation in randomized clinical trials.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03281499.
Topics: Humans; Male; Female; Robotic Surgical Procedures; Middle Aged; Neoplasms, Unknown Primary; Aged; Prospective Studies; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Oropharyngeal Neoplasms; Head and Neck Neoplasms; Radiotherapy Dosage
PubMed: 38602692
DOI: 10.1001/jamaoto.2024.0423 -
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke... Apr 2024To explore the efficacy and safety of immunoneoadjuvant therapy with pembrolizumab combined with chemotherapy in locally advanced resectable hypopharyngeal squamous...
To explore the efficacy and safety of immunoneoadjuvant therapy with pembrolizumab combined with chemotherapy in locally advanced resectable hypopharyngeal squamous cell carcinoma patients. This study was a prospective, single arm, single center clinical study that was opened for enrollment in April 2021. Patients who met the inclusion criteria at the Cancer Hospital of the Chinese Academy of Medical Sciences were treated with neoadjuvant therapy of pembrolizumab combined with cisplatin and paclitaxel, and after treatments, received surgery and postoperative adjuvant therapy. The main endpoint of this study was postoperative pathological complete response (pCR), and other observations included adverse reactions and long-term prognoses of patients after neoadjuvant therapy. By September 2023, a total of 23 patients who underwent neoadjuvant therapy and surgery were enrolled in the study and all patients were males aged 49-74 years. All patients were locally advanced stage, including 3 patients in stage Ⅲ and 20 patients in stage Ⅳ. There were 12 cases of primary lesions with posterior ring involvement accompanied by fixation of one vocal cord and 20 cases of regional lymph node metastases classified as N2. Eighteen cases received a two cycle regimen and 5 cases received a three cycle regimen for neoadjuvant therapy. The postoperative pCR rate was 26.1% (6/23), with no surgical delay caused by adverse drug reactions. The laryngeal preservation rate was 87.0% (20/23). Pharyngeal fistula was the main surgical complication, with an incidence of 21.7% (5/23). The median follow-up time was 15 months, and 3 patients experienced local recurrence. The immunoneoadjuvant therapy of pembrolizumab combined with chemotherapy has a high pCR rate in locally advanced resectable hypopharyngeal squamous cell carcinoma, with increased laryngeal preservation rate and no significant impact on surgical safety.
Topics: Male; Humans; Female; Neoadjuvant Therapy; Squamous Cell Carcinoma of Head and Neck; Prospective Studies; Antineoplastic Combined Chemotherapy Protocols; Head and Neck Neoplasms; Immunotherapy
PubMed: 38599640
DOI: 10.3760/cma.j.cn115330-20231015-00147 -
International Journal of Radiation... Apr 2024Recurrent head and neck cancer presents a therapeutic challenge because of cumulative toxicity from initial radiation therapy, limiting reirradiation options. Boron...
Clinical Results and Prognostic Factors in Boron Neutron Capture Therapy for Recurrent Squamous Cell Carcinoma of the Head and Neck Under the Japan National Health Insurance System: A Retrospective Study of the Initial 47 Patients.
PURPOSE
Recurrent head and neck cancer presents a therapeutic challenge because of cumulative toxicity from initial radiation therapy, limiting reirradiation options. Boron neutron capture therapy (BNCT) offers a promising alternative, selectively delivering a radical dose to tumors while sparing adjacent normal tissue. This study investigates the initial clinical outcomes and prognostic factors associated with BNCT for recurrent squamous cell carcinoma of the head and neck.
METHODS AND MATERIALS
This retrospective analysis investigated the initial 47 patients treated with BNCT between May 2020 and February 2021 in Japan. All patients had received radiation therapy with a median dose of 70 Gy (range, 44-176) before BNCT. Median tumor size was 11 cm (range, 1-117 cm), with 23% of tumors larger than 30 cm, and 87% of patients had prior systemic therapy. The most common prescribed dose to the pharyngeal mucosa was 15 Gy-Eq (36%), followed by 18 Gy-Eq (34%). The minimum dose given to tumor was 27.4 Gy-Eq (range, 13.3-45.2). In 23 patients, F-fluoro-borono-phenylalanine positron emission tomography was performed within 1 week before BNCT, and the tumor-to-blood B ratio was 3.5 (range, 2.0-8.7).
RESULTS
Efficacy analysis revealed a 51% complete response rate and a 74% overall response rate. Disease-free survival rates at 1 and 2 years were 34.6% and 26.6%, respectively. Overall survival rates at 1 and 2 years were 86.1% and 66.5%, respectively. Multivariate analysis revealed that, among the patient characteristics, whether the lesion was mucosal had a significant effect on achieving complete response.
CONCLUSIONS
This study provided valuable insights into the early integration of BNCT into routine clinical practice, highlighting its efficacy and safety. Technical improvements are needed to ensure precise dose administration. Ongoing prospective studies, such as the phase II REBIVAL study, will further elucidate the role of BNCT in recurrent head and neck cancer.
PubMed: 38580084
DOI: 10.1016/j.ijrobp.2024.03.041 -
Laryngo- Rhino- Otologie Apr 2024
Topics: Humans; Carcinoma; Pharyngeal Neoplasms
PubMed: 38565103
DOI: 10.1055/a-2219-0522 -
Laryngo- Rhino- Otologie Apr 2024
Topics: Humans; Carcinoma; Pharyngeal Neoplasms
PubMed: 38565102
DOI: 10.1055/a-2219-0448 -
The Lancet. Oncology May 2024Despite multimodal therapy, 5-year overall survival for locally advanced head and neck squamous cell carcinoma (HNSCC) is about 50%. We assessed the addition of... (Randomized Controlled Trial)
Randomized Controlled Trial
Pembrolizumab plus concurrent chemoradiotherapy versus placebo plus concurrent chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (KEYNOTE-412): a randomised, double-blind, phase 3 trial.
BACKGROUND
Despite multimodal therapy, 5-year overall survival for locally advanced head and neck squamous cell carcinoma (HNSCC) is about 50%. We assessed the addition of pembrolizumab to concurrent chemoradiotherapy for locally advanced HNSCC.
METHODS
In the randomised, double-blind, phase 3 KEYNOTE-412 trial, participants with newly diagnosed, high-risk, unresected locally advanced HNSCC from 130 medical centres globally were randomly assigned (1:1) to pembrolizumab (200 mg) plus chemoradiotherapy or placebo plus chemoradiotherapy. Randomisation was done using an interactive response technology system and was stratified by investigator's choice of radiotherapy regimen, tumour site and p16 status, and disease stage, with participants randomly assigned in blocks of four per stratum. Participants, investigators, and sponsor personnel were masked to treatment assignments. Local pharmacists were aware of assignments to support treatment preparation. Pembrolizumab and placebo were administered intravenously once every 3 weeks for up to 17 doses (one before chemoradiotherapy, two during chemoradiotherapy, 14 as maintenance therapy). Chemoradiotherapy included cisplatin (100 mg/m) administered intravenously once every 3 weeks for two or three doses and accelerated or standard fractionation radiotherapy (70 Gy delivered in 35 fractions). The primary endpoint was event-free survival analysed in all randomly assigned participants. Safety was analysed in all participants who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03040999, and is active but not recruiting.
FINDINGS
Between April 19, 2017, and May 2, 2019, 804 participants were randomly assigned to the pembrolizumab group (n=402) or the placebo group (n=402). 660 (82%) of 804 participants were male, 144 (18%) were female, and 622 (77%) were White. Median study follow-up was 47·7 months (IQR 42·1-52·3). Median event-free survival was not reached (95% CI 44·7 months-not reached) in the pembrolizumab group and 46·6 months (27·5-not reached) in the placebo group (hazard ratio 0·83 [95% CI 0·68-1·03]; log-rank p=0·043 [significance threshold, p≤0·024]). 367 (92%) of 398 participants treated in the pembrolizumab group and 352 (88%) of 398 participants treated in the placebo group had grade 3 or worse adverse events. The most common grade 3 or worse adverse events were decreased neutrophil count (108 [27%] of 398 participants in the pembrolizumab group vs 100 [25%] of 398 participants in the placebo group), stomatitis (80 [20%] vs 69 [17%]), anaemia (80 [20%] vs 61 [15%]), dysphagia (76 [19%] vs 62 [16%]), and decreased lymphocyte count (76 [19%] vs 81 [20%]). Serious adverse events occurred in 245 (62%) participants in the pembrolizumab group versus 197 (49%) participants in the placebo group, most commonly pneumonia (43 [11%] vs 25 [6%]), acute kidney injury (33 [8%] vs 30 [8%]), and febrile neutropenia (24 [6%] vs seven [2%]). Treatment-related adverse events led to death in four (1%) participants in the pembrolizumab group (one participant each from aspiration pneumonia, end-stage renal disease, pneumonia, and sclerosing cholangitis) and six (2%) participants in the placebo group (three participants from pharyngeal haemorrhage and one participant each from mouth haemorrhage, post-procedural haemorrhage, and sepsis).
INTERPRETATION
Pembrolizumab plus chemoradiotherapy did not significantly improve event-free survival compared with chemoradiotherapy alone in a molecularly unselected, locally advanced HNSCC population. No new safety signals were seen. Locally advanced HNSCC remains a challenging disease that requires better treatment approaches.
FUNDING
Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.
Topics: Humans; Antibodies, Monoclonal, Humanized; Double-Blind Method; Chemoradiotherapy; Male; Squamous Cell Carcinoma of Head and Neck; Female; Middle Aged; Aged; Head and Neck Neoplasms; Antineoplastic Agents, Immunological; Progression-Free Survival; Adult
PubMed: 38561010
DOI: 10.1016/S1470-2045(24)00100-1 -
Journal of Cancer Research and... Jan 2024Hepatocellular carcinoma (HCC) is a highly malignant tumor with frequent intrahepatic and extrahepatic metastases. Extrahepatic metastasis occurs in one-third of...
Hepatocellular carcinoma (HCC) is a highly malignant tumor with frequent intrahepatic and extrahepatic metastases. Extrahepatic metastasis occurs in one-third of patients with HCC and indicates a dismal prognosis. The head and neck region is an extremely uncommon site of metastatic HCC. Extrahepatic metastasis at first presentation, although uncommon, indicates advanced disease with a poor prognosis. Herein, we present the case of a 68-year-old male patient with a neck mass. Clinical examination and initial radiology were suggestive of an advanced primary pharyngeal malignancy. Biopsy showed neoplasm with large polygonal cells with clear/granular cytoplasm. The neoplastic cells showed positivity for Hep Par1, CD10, and CEA. A diagnosis of metastatic HCC was given. Subsequently, serum alpha-fetoprotein level was found to be markedly elevated and further imaging showed multiple mass lesions in the liver. It is necessary to recognize that the pharyngeal region is a potential site of HCC metastasis. Accurate diagnosis and risk stratification can help in avoiding unnecessary costs and delay in treatment.
Topics: Male; Humans; Aged; Carcinoma, Hepatocellular; Liver Neoplasms; Prognosis; Hypopharyngeal Neoplasms; Pharyngeal Neoplasms
PubMed: 38554358
DOI: 10.4103/jcrt.jcrt_1655_22 -
Journal of Ultrasound Mar 2024Masses in the parapharyngeal area are rare and often due to infectious phenomena arising from the oral cavity or pharynx which lead to abscess formation. Less...
Masses in the parapharyngeal area are rare and often due to infectious phenomena arising from the oral cavity or pharynx which lead to abscess formation. Less frequently, the lesion can be neoplastic. Tumours of the parapharyngeal space are rare, accounting for less than 1% of all head and neck neoplasms. We report the case of a patient who came to our observation for mandibular pain. Multiparametric diagnostic imaging was done thus showing a parapharyngeal mass. An ultrasound guided biopsy was performed by a transcutaneous route with a high median approach at neck level, to characterize the mass in the right tonsillar region. The histological examination reported the final histological diagnosis of sarcomatoid carcinoma.
PubMed: 38551781
DOI: 10.1007/s40477-024-00882-z -
Auris, Nasus, Larynx Jun 2024Transoral surgery is a minimally invasive treatment but may cause severe dysphagia at a lower rate than chemoradiotherapy.
OBJECTIVE
Transoral surgery is a minimally invasive treatment but may cause severe dysphagia at a lower rate than chemoradiotherapy.
METHODS
We compared clinical information, surgical complications, and swallowing function in patients who underwent transoral nonrobotic surgery for laryngo-pharyngeal squamous cell carcinoma between 2015 and 2021 in a multicenter retrospective study.
RESULTS
Six hundred and forty patients were included. Postoperative bleeding was observed in 20 cases (3.1%), and the risk factor was advanced T category. Postoperative laryngeal edema was observed in 13 cases (2.0%), and the risk factors were prior radiotherapy, advanced T stage, and concurrent neck dissection in patients with resected HPC. Dysphagia requiring nutritional support was observed in 29 cases (4.5%) at 1 month postoperatively and in 19 cases (3.0%) at 1 year postoperatively, respectively. The risk factors for long-term dysphagia were prior radiotherapy and advanced T category. Short-term risk factors for dysphagia were prior radiotherapy, advanced T category, and concurrent neck dissection, while long-term risk factors for dysphagia were only prior radiotherapy and advanced T category.
CONCLUSION
Prior radiotherapy, advanced T stage, and concurrent neck dissection increased the incidence of postoperative laryngeal edema and short-term dysphagia, but concurrent neck dissection did not affect long-term dysphagia. Such features should be considered when considering the indication for transoral surgery and postoperative management.
Topics: Humans; Male; Retrospective Studies; Deglutition Disorders; Female; Laryngeal Neoplasms; Middle Aged; Aged; Postoperative Complications; Neck Dissection; Pharyngeal Neoplasms; Risk Factors; Squamous Cell Carcinoma of Head and Neck; Neoplasm Staging; Adult; Laryngeal Edema; Carcinoma, Squamous Cell; Postoperative Hemorrhage; Aged, 80 and over; Natural Orifice Endoscopic Surgery
PubMed: 38547566
DOI: 10.1016/j.anl.2024.03.005 -
Discovery Medicine Mar 2024Identifying the key molecular targets in hypopharynx squamous cell carcinoma (HSCC) is crucial for understanding this prevalent and highly fatal type of head and neck...
BACKGROUND
Identifying the key molecular targets in hypopharynx squamous cell carcinoma (HSCC) is crucial for understanding this prevalent and highly fatal type of head and neck tumor. The study aims to enhance comprehension of the HSCC process by accurately identifying these key molecular targets.
MATERIALS AND METHODS
In this study, we examined 47 clinical tissue samples from individuals diagnosed with HSCC using RNA-seq high-throughput assay. Quantitative real-time PCR (RT-PCR) was used to compare long non-coding RNA (lncRNA) bladder cancer-associated transcript 1 () expression in HSCC tissues versus adjacent non-tumor tissues. The influence of highly expressed lncRNA on prognostic survival was assessed. Subsequently, we cultured human pharynx squamous cell carcinoma FaDu cells. After reducing lncRNA expression, we assessed FaDu cell proliferation, invasion, and migration using Cell Counting kit-8 (CCK-8) assay, colony formation assay, EUD assay, Transwell assay, and scratch assay. Additionally, liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS) and western blotting analysis were used to analyze proteins that bind to lncRNA . During experiments, mice received subcutaneous injections of FaDu cells transfected with lncRNA shRNA or Scr plasmid (Control) in the dorsal region to observe and compare tumor growth. Lastly, tumor tissues underwent hematoxylin-eosin (HE) and immunohistochemical (IHC) staining.
RESULTS
lncRNA was screened as one of the most significant genes among the group of differentially expressed lncRNAs. RT-PCR exhibited elevated lncRNA expression in HSCC tissues when compared to non-tumor tissues ( < 0.001). Furthermore, increased lncRNA expression correlated with advanced clinical stages, heightened lymphatic invasion, and a poor prognosis. Subsequent experiments solidified our observations, demonstrating lncRNA 's promotion of HSCC cell proliferation ( < 0.05), migration ( < 0.01), and invasion ( < 0.01) compared with the control group. Moreover, LC-MS/MS identified signal transducer and activator of transcription 3 (STAT3) and Prohibitin 2 (PHB2) as lncRNA -binding proteins and sh-lncRNA inhibits STAT3/AKT phosphorylation ( < 0.01) and alters the subcellular distribution of PHB2 and P21 compared with the control group ( < 0.01). Moreover, experiments showed that lncRNA inhibition suppresses tumorigenicity in an HSCC xenograft model compared to the control group ( < 0.01).
CONCLUSIONS
lncRNA is highly expressed in HSCC tumor tissues and plays a crucial role in the development of HSCC and . This increased expression may be caused by STAT3/AKT pathway activation, consequently inhibiting P21 expression through PHB2.
Topics: Humans; Animals; Mice; RNA, Long Noncoding; Chromatography, Liquid; Hypopharynx; Proto-Oncogene Proteins c-akt; Tandem Mass Spectrometry; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Urinary Bladder Neoplasms; Cell Proliferation; Cell Line, Tumor; Cell Movement; Gene Expression Regulation, Neoplastic
PubMed: 38531795
DOI: 10.24976/Discov.Med.202436182.51