cell therapies

2025-04-25 | Abstract CT058: Final results of a first-in-human (FIH) study of intratumoral pan-ErbB-targeted CAR-T cell therapy for head and neck squamous cell carcinoma (HNSCC): T4 immunotherapy

Abstract Background: Advanced HNSCC has a dismal prognosis despite multiagent treatment. Epidermal growth factor receptor (EGFR, ErbB-1) is upregulated in most tumors, although EGFR-targeted therapy yields modest benefit. Other ErbB family members are commonly co-expressed, providing a rationale for targeting of the extended ErbB network in HNSCC. We present final toxicity and response data for this FIH dose escalation trial of intratumorally administered pan-ErbB-targeting CAR-T cells (T4 immunotherapy) in patients (pts) with advanced HNSCC. Methods: Eligible pts had locally advanced, recurrent or metastatic HNSCC (excluding brain), accessible tumor site(s) for T4 administration and radiologically measurable disease. Peripherally harvested T cells were transduced to co-express pan-ErbB-targeting CAR T1E28ζ and chimeric IL-4/IL-2 receptor 4αβ. Cells were expanded ex vivo in IL-4 to generate T4 immunotherapy, which was injected as a fresh product into single or multiple locoregional tumor sites. Doses ranged from 1×107 to 1×109 cells across 7 cohorts, using 3+3 dose escalation in cohorts 1-5. Cohorts 6 and 7 received 1×108 cells preceded by lymphodepleting (LD) cyclophosphamide and fludarabine chemotherapy. Cohort 7 received additional nivolumab 480mg q4w for 3 cycles. Primary endpoint was dose limiting toxicity (DLT) within 28d. Secondary endpoints included radiologic response at 6w, presence of tumoral and circulating T4+ T cells and serum and tumoral immunomodulatory markers. Results: 19 pts (median age, 62; M:F,15:4) received T4 immunotherapy: 3 in each cohort 1-6 and 1 in cohort 7. Site of origin was oral cavity in 11 (57.9%), oropharynx, 4 (21.1%); nasopharynx, 2 (10.5%); hypopharynx and occult primary 1 each (5.3%). Pts had received a median of 2 (1-5) prior treatment lines. No DLTs were observed. All pts experienced TRAEs, largely G1/2; most common were local swelling, pain or infection, fever, CRS, chills, fatigue and nausea, with cytopenias in LD cohorts. Of 4 instances of CRS, 3 were G1 and 1 was G2. At 6 weeks, 10 pts (52.6%) had stable disease and 9 (47.4%) had progressed, with no association with T4 dose, LD or nivolumab. There were no radiologic responses though softer tumor consistency was noted in several pts. Median overall survival (mOS) was >10m. Subsequent treatments included palliative radiotherapy, chemotherapy +/- cetuximab, electrochemotherapy or trial in 8 pts; no treatment, 4; unknown, 3. One pt had a durable complete response to subsequent local injection of talimogene laherparepvec with pembrolizumab. Conclusions: Intratumoral pan-ErbB-directed CAR-T cell injection was well tolerated and associated with disease stability in heavily pretreated HNSCC. mOS was longer than that expected for this cohort. The lack of radiologic responses highlights the need for improved advanced cell therapies for solid tumors. Citation Format: Cienne Morton, Fiona Wang, Sophie Papa, Antonella Adami, Michael Metoudi, Daniela Achkova, Fiona Reid, Maria Elstad, Nicholas Beckley-Hoelscher, Abdel Douiri, Marc Delord, Mike Lyne, Dharshene Shivapatham, Aysar Al-Rawi, Christopher Fisher, Andrew Hope, Sakina Gooljar, Arindam Mitra, Linda Gomm, Ana C. Parente-Pareira, David M. Davies, Farzin Farzaneh, Teresa Guerrero-Urbano, Jean-Pierre Jeannon, James Spicer, John Maher. Final results of a first-in-human (FIH) study of intratumoral pan-ErbB-targeted CAR-T cell therapy for head and neck squamous cell carcinoma (HNSCC): T4 immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT058.

Open article ↗

2024-09-01 | 802. TECHNICAL DETAILS: FREE JEJUNAL GRAFT AND REVERSE SAPHENOUS VEIN GRAFT FOR RECONSTRUCTION AFTER TOTAL PHARYNGO-LARYNGECTOMY AND PROXIMAL ESOPHAGECTOMY

Abstract Background We would like to show our tips for free jejunal graft and vascular reconstruction after pharyngo-laryngectomy and proximal esophagectomy. Methods 65 years-old man with history of hypopharynx squamous cell carcinoma cT3 cN0 cM0 who underwent radical Qt/Rt with initially complete response. After 2 years follow-up, he presented dysphagia and recurrence of squamous cell carcinoma proven by histology. Upper endoscopy shows cervical esophageal stenosis due to tumor infiltration. Rescue surgery was decided after systemic dissemination was ruled out with PET-CT. Results Pharyngo-laryngectomy, total thyroidectomy and proximal esophagectomy was performed. Free margin tumor was confirmed by frozen section. Jejunal segment with adequate vascular supply is selected, preferable with a single artery and vein. Peristaltic direction of the jejunum is marked to avoid mistakes during graft transposition. Division of mesenteric branches to prevent postoperative bleeding. Before jejunal section we recommend administration of hyoscine butilbromide 20 mg iv to avoid jejunal spams. Measuring the length graft needed before dividing the jejunum to avoid redundant or short graft is recommended. We must carefully isolate the pedicle avoiding damaging blood supply. To reduce time of ischemia, jejunal graft pedicle should not be ligated until cervical dissection is completed and we have ruled out if venous graft may be needed. After cervical artery and vein dissection, we ensure adequate blood flow and heparinize vessels before clipping. When dividing the pedicle, artery should be divided before the vein to avoid venous congestion, posteriorly we must heparinize the vessels. Povidone-iodine intraluminal washing is recommended. Jejuno-jejunal anastomosis for GI tract restoration. GI reconstruction first is recommended to avoid unnecessary traction on the vascular anastomosis. After ensuring adequate direction of the jejunal graft jejuno-esophageal anastomosis is performed with interrupted suture. Pharyngo-jejunal anastomosis is performed with barbed 3-0 running suture for anterior and posterior layer. Methylene blue test is performed for check the anastomosis. Vascular reconstruction technique depends on the vascular anatomical variations and availability. In this case, superior thyroid artery and sublingual vein were available. Saphenous vein graft might be needed, this graft must be used in reverse way to avoid the vein valves and length must be adjusted. Venous anastomosis should be performed before than arterial reconstruction after heparinize solution in both vessels to avoid thrombosis. Conclusion Free jejunal graft is a highly complex procedure that must be extremely coordinated and protocolized to avoid longer time of ischemia and risk of thrombosis that might compromise the graft viability. https://1drv.ms/v/s!AmFrct07P6MP1Fbyh_7Ce_OK5bB8?e=OMSjsK

Open article ↗

2024-06-30 | LARYNGOPHARYNGEAL RECONSTRUCTION IN A PREGNANT WOMAN: A CLINICAL CASE

Relevance: Cancer in pregnancy is a very serious clinical condition that seriously affects women and their families, as well as the medical staff who provide care. Diagnostic and therapeutic solutions must balance the appropriate treatment with the risk to the fetus. In developed countries, cancer in pregnant women has become more common over the past 30 years due to an increase in the number of older women giving birth. Melanoma, lymphoma, leukemia, and cancers of the breast, cervix, ovaries, gastrointestinal tract, and genitourinary system are the most common malignant neoplasms in pregnant women. Head and neck cancers are rare in pregnancy. A total of 3 cases of locally advanced laryngopharyngeal cancer were recorded in patients aged 23 to 28 years in 2017-2023 at the State Clinical Hospital of the Akimat of Astana Multidisciplinary Medical Center. This article describes a case of advanced squamous cell carcinoma of the laryngeal region in a young pregnant woman and also discusses the diagnosis and treatment of head and neck cancer in pregnant women. The study aimed to describe a clinical case of squamous cell carcinoma of the larynx in a pregnant patient. Methods: The description of a clinical case presents data from laboratory, instrumental, and physical research methods of a pregnant patient with hypopharynx squamous cell carcinoma, who was examined, treated, and followed up at the State Clinical Hospital of the Akimat of Astana Multidisciplinary Medical Center. The patient was diagnosed with IVA laryngopharyngeal cancer T4aN2cM0. Grade III dysphagia. Laryngeal stenosis. Grade II cachexia” and received three courses of neoadjuvant polychemotherapy. Then, she underwent surgical intervention in the volume of laryngopharyngectomy and reconstructive surgery using a free radial flap and was administered adjuvant external beam radiation therapy. Results: The article presents the results of laryngopharyngectomy for locally advanced squamous cell carcinoma of the hypopharynx. The postoperative period was without complications, the patient was discharged 14 days after surgery in satisfactory condition and continued adjuvant radiation therapy. Conclusions: The reviewed clinical case demonstrates the importance of an integrated approach to treating laryngopharyngeal cancer, including effective reconstruction of postoperative defects using free fasciocutaneous flaps.

Open article ↗

2021-04-15 | Free partial patch and partial tube jejunal graft transfers were used to reconstruct pharyngoesophageal defect: Our experience with three cases

Those patients with hypopharyngoesophageal cancer often sacrificed larynx before reconstruction using jejunum to restore the continuity of the digestive tract and allow oral alimentation. We retrospectively collected and analyzed three patients who underwent hypopharyngoesophageal reconstruction by free partial patch and partial tube jejunal graft transfer with reservation of laryngeal function caused by hypopharyngeal cancer invading the cervical esophagus. The partial patch and partial tube jejunal graft transfer survival rate was 100%(3/3). The larynx was reserved in the three patients. The partial patch and partial tube jejunal graft transfer is a safe and reliable choice for reconstruction of large and complex defects after pharyngectomy and cervical esophagectomy with larynx preserved.

Open article ↗

2017-12-01 | Efficacy of Tensed and Straight Free Jejunum Transfer for the Reduction of Postoperative Dysphagia

Background: Free jejunal transfer (FJT) is a standard method of reconstruction after total pharyngo-laryngo-cervical esophagectomy (TPLE) in patients with advanced head and neck cancer. However, it is related to various degrees of postoperative swallowing dysfunction. This study aimed to assess whether the tensed and straight FJT method results in a reduced rate of postoperative dysphagia compared with historical controls. Methods: Patients who were undergoing FJT after TPLE for squamous cell carcinoma of the hypopharynx or cervical esophagus were enrolled. The primary endpoint was the rate of not developing dysphagia within 6 months of the surgery, and we compared this value with that obtained from historical data of patients who underwent FJT. The secondary endpoint was the rate of developing surgical complications. Results: Although 128 patients were registered between August 2012 and July 2015, 7 were excluded based on the exclusion criteria. Of the remaining 121 patients, FJT with the craniocaudally tensed and straight method was performed in all patients. The rate of not developing dysphagia and its 95% confidence interval (CI) were 66.1% and 57.0–74.5%, respectively. The lower limit of the CI was higher than the prespecified threshold value of 50.0%. The rate of developing complications of total necrosis of the jejunum was 3.3%, cervical infection was 9.9%, and major anastomotic leakage was 4.1%. Conclusions: Our findings revealed that the proportion of postoperative dysphagia decreased in patients who underwent tensed and straight FJT. This method may become the standard surgical method in reconstruction of defects after TPLE.

Open article ↗

small molecules

2026-08-01 | Three-weekly Cisplatin versus Weekly Cisplatin Concurrently with Accelerated Radiotherapy Fractionation in Head and Neck Cancers: A Prospective Interventional Study

Introduction: Concurrent chemoradiation is the standard of care for locally advanced head and neck squamous cell carcinoma. Cisplatin remains the primary radiosensitiser, enhancing tumour cell kill through multiple mechanisms. Altered fractionation, combined with concurrent chemotherapy, has demonstrated superior outcomes compared with conventional schedules. Accelerated fractionation is increasingly adopted; however, the optimal concurrent cisplatin schedule remains uncertain. Aim: To compare acute toxicity and early treatment response between three-weekly and weekly cisplatin concurrently with accelerated fractionation in Head and Neck Cancers (HNC). Materials and Methods: The present prospective interventional feasibility study was conducted in the Department of Radiation Oncology, Maharishi Markandeshwar Institute of Medical Sciences and Research (MMIMSR), Mullana, Ambala, Haryana, India. between 1st July 2021 and 30th June 2022. A total of 43 non-metastatic, histopathologically confirmed squamous cell carcinoma patients of the oropharynx, hypopharynx, and larynx (Stage II-IVB) were randomised using computer-based block randomisation into two arms. The three-weekly arm received accelerated radiotherapy (70 Gy in 35 fractions, six fractions per week) with cisplatin 100 mg/m² on days 1 and 22. The weekly arm received the same radiotherapy with cisplatin 40 mg/m² on days 1, 8, 15, 22, 29, and 36. Forty patients were analysed (20 per arm); Toxicities (dermatitis, mucositis, dysphagia, xerostomia, haematologic (using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0), renal parameters (using Kidney Disease: Improving Global Outcomes (KDIGO) criteria) and vomiting (using a predefined subjective clinical classification) were assessed and compared between the two arms. Response assessment was done and compared using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. For Quality of Life (QoL) assessment and comparisons, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Head and Neck Module (35 items) (EORTC QLQ-H&N35) questionnaires were used. For comparison, 3-month outcomes were considered. Pearson’s chi-square test was used to compare categorical variables. Continuous variables were compared using the unpaired Student’s t-test. A p-value of <0.05 was considered statistically significant. Results: The mean age of the study population was 54.50±8.4 years (42-70 years), 95% (38 out of 40) of patients were males. All patients in the three-weekly arm received 200 mg/m² cumulative cisplatin, whereas 90% in the weekly arm received >200 mg/m² (p=0.001). Radiotherapy interruptions occurred in 15% versus 5%, respectively. Median Overall Treatment Time (OTT) was similar (40.5 vs 41.5 days; p=0.98). At three months, complete response rates were 65% (three-weekly) and 50% (weekly) (p=0.66). Grade ≥3-mucositis was higher in the three-weekly arm (40% vs 25%; p=0.040). Xerostomia was significantly greater in the three-weekly arm at treatment completion and three months (p<0.05). Conclusion: Both regimens were effective. Weekly cisplatin arm achieved higher cumulative dosing with a more favourable toxicity profile. Although response rates numerically favoured the three-weekly arm, differences were not statistically significant.

Open article ↗

2026-05-29 | Current status and future perspectives of treatment de-escalation in localized head and neck cancer

Head and neck squamous cell carcinoma (HNSCC) often requires invasive multimodal therapy, including surgery, radiotherapy, and chemotherapy. Although these interventions have improved treatment outcomes, patients frequently experience long-term functional impairment and treatment-related morbidity. Consequently, clinical research has shifted toward treatment de-escalation, a paradigm aimed at preserving quality of life while maintaining oncologic control. This review summarizes the current evidence from prospective clinical trials on de-escalation strategies for HNSCC of the oropharynx, hypopharynx, larynx, and oral cavity, with a focus on radiotherapy-based approaches. Investigators have evaluated several de-escalation strategies, including total radiation dose reduction in definitive chemoradiotherapy, modification or omission of concurrent systemic therapy, de-intensification of prophylactic nodal irradiation, response-adapted treatment de-intensification, and minimally invasive approaches such as transoral surgery with risk-adapted postoperative therapy. These strategies target favorable-risk populations, particularly patients with human papillomavirus-associated oropharyngeal cancer. Although numerous phase II studies have reported encouraging clinical outcomes and acceptable toxicity profiles, definitive evidence supporting the safety and efficacy of de-escalation strategies remains unestablished in large-scale phase III trials. Unwarranted de-escalation for HNSCC should be avoided, particularly for medically fit patients, and promising strategies require validation in phase III trials before routine clinical adoption. Future challenges include prospective validation through clinical trials and the integration of predictive biomarkers to balance the delicate trade-off between toxicity reduction and oncologic safety.

Open article ↗

2026-05-28 | A phase II trial of a novel induction regimen: Polymeric micellar paclitaxel plus cisplatin for locally advanced head and neck squamous cell carcinoma.

e18067 Background: Induction chemotherapy with the TPF regimen is recommended by international guidelines for locally advanced head and neck squamous cell carcinoma. However, its significant toxicities lead to generally poor patient tolerance, limiting its widespread clinical application, particularly among elderly or medically unfit patients. By encapsulating paclitaxel within micelles, pm-Pac enhanced permeability and retention effect, thereby improving pharmacokinetics and tumor-targeted delivery. This study evaluated the efficacy and safety of induction therapy with polymeric micellar paclitaxel plus cisplatin in LA-SCCHN, aiming to determine whether its pharmacologic advantages translate into clinical benefit. Methods: According to clinical trail the Eligible patients were stage III to IVB HNSCC received polymeric micellar paclitaxel 230 mg/m² (Day 1) plus cisplatin 70 mg/m² (Day 1–2) every three weeks for 2–4 cycles. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), safety, adverse events (AEs), and completion of subsequent definitive therapy. Results: Thirty patients were enrolled (median age, 66 years), including five HPV-positive cases (16.7%). After induction therapy, 5 patients achieved complete response (CR) and 11 achieved partial response (PR), yielding an ORR of 53.3% and a DCR of 93.3%. ORR reached 80% in HPV-positive patients versus 48% in HPV-negative/unknown patients. Common AEs included myalgia/limb pain (60%), neutropenia (26.7%), and bone marrow suppression (33.3%). Grade ≥3 AEs were mainly hematologic; no solvent-related hypersensitivity reactions occurred. Conclusions: Polymeric micellar paclitaxel plus cisplatin demonstrated promising antitumor activity, high disease control, and favorable tolerability in patients with LA-SCCHN, particularly among elderly or TPF-intolerant individuals. Clinical trial information: ChiCTR2500110591. Variable Number (n=30) Percentage (%) Age, years Median 66 (range 35–77) — <65 12 40.0 ≥65 18 60.0 Sex Male 23 76.7 Female 7 23.3 Primary Tumor Site Hypopharynx 9 30.0 Larynx 8 26.7 Oropharynx 6 20.0 Oral cavity 4 13.3 Other* 3 10.0 Clinical Stage II 2 6.7 III 13 43.3 IVA 14 46.7 IVB 1 3.3 HPV Status Positive 5 16.7 Negative/Unknown 25 83.3 Response Number (n=30) Percentage (%)

Open article ↗

2026-05-27 | Inferring optimal detection of homozygous loss (homozygous deletion) in head and neck cancer: Associations with HPV status, primary disease site, and clinical outcomes.

6071 Background: Validated detection of homozygous loss is becoming increasingly important in clinical practice. Examples include targeting the AKT pathway in breast cancer with PTEN loss and ongoing multi-tumor trials of PRMT5 and MAT2A inhibitors, with MTAP loss serving as a key biomarker. Homozygous losses are challenging to detect and require intentional next-generation sequencing assay design and validation. We evaluated the prevalence of the most common homozygous losses in advanced head and neck squamous cell carcinoma (HNSCC) and their associations with HPV status, primary site, and clinical outcomes on standard first-line (1L) therapies. Methods: This study used the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine head and neck cancer clinico-genomic database (FH-FMI CGDB), originating from approximately 280 US cancer clinics (~800 sites of care). Patients with advanced HNSCC who underwent tissue-based genomic profiling with FoundationOneCDx were included. First-line therapy included chemotherapy alone or in combination with cetuximab or immune checkpoint inhibitors (ICIs). Logistic regression assessed the associations of prior treatment, HPV status, and primary disease site with homozygous losses. Clinical outcomes were evaluated with Cox proportional hazards models. Results: Among 969 HNSCC specimens, homozygous losses were most frequent in CDKN2A (22.1%), CDKN2B (17.8%), MTAP (9.4%), and PTEN (5.3%). CDKN2A, CDKN2B and MTAP losses were enriched in tumors arising from the larynx and hypopharynx compared with the oral cavity and oropharynx and were largely mutually exclusive with HPV positivity. PTEN loss was most common in the oropharynx and was enriched in HPV-positive tumors and in metastatic liver biopsies. In univariable analysis, homozygous losses were not associated with outcomes after 1L therapy. In multivariable analysis, HPV negativity and higher ECOG scoring, but not PD-L1 status, were independently associated with worse overall survival. Conclusions: Using an assay that is FDA-approved to detect and report copy-number (CN) losses, homozygous losses of CDKN2A , CDKN2B , MTAP , and PTEN were frequently observed in HNSCC. These alterations were not directly associated with outcomes following 1L therapy. Similar to CDKN2A/B loss , MTAP loss was enriched in HPV-negative tumors and defines a clinically relevant subset of HNSCC (~10%) potentially eligible for emerging MTAP-targeted therapies.

Open article ↗

2026-05-03 | Lymphoepithelial carcinoma of the esophagus with primary squamous cell carcinoma of the hypopharynx: complete response was achieved by chemoradiation therapy.

A 52-year-old male presented with a 3-month history of dysphagia. Laryngological examination showed a left-sided hypopharyngeal tumor, and biopsy of biopsy the tumor revealed moderately differentiated squamous cell carcinoma (SCC). Computed tomography (CT) and esophagogastroduodenoscopy also revealed a 50 mm mass in the middle thoracic esophagus. Biopsy of the esophageal tumor revealed lymphoepithelial carcinoma (LEC), characterized by lymphoplasmacytic infiltration and atypical immunohistochemical markers: The infiltrated cells were positive for EMA, partially positive for cytokeratin (CK) AE1/AE3, slightly positive for p63, and negative for CK5/6, synaptophysin, chromogranin A, CK7, p40, S100, HMB45, Melan A, and EBER-ISH. The patient underwent chemoradiotherapy (CRT) with 50.4 Gy in 24 fractions and concurrent chemotherapy with cisplatin and 5-fluorouracil. After CRT, both the tumors showed complete resolution on CT and endoscopy. No recurrence has been observed for 17 months. LEC, often associated with Epstein-Barr virus (EBV), is extremely rare in the esophagus. To our knowledge, this is the first reported case of coexistence of esophageal LEC and primary hypopharyngeal SCC, in which complete response was achieved by CRT.

Open article ↗

antibodies

2026-08-12 | Impact of combined positive score in cetuximab plus chemotherapy in recurrent/metastatic head and neck cancer: A real-world study

Objectives: Head and neck cancers (HNCs) are a significant global health issue, particularly in India. Squamous cell carcinoma of the head and neck (SCCHN) accounts for 90% of all HNC cases and includes a diverse range of cancers originating from the lip, oral cavity, hypopharynx, nasopharynx, oropharynx, larynx, and salivary glands. This real-world study evaluated the impact of programmed cell death ligand-1 combined positive score (CPS) on treatment outcomes in Indian patients with recurrent/metastatic (R/M) SCCHN treated with cetuximab-based chemotherapy. Material and Methods: This retrospective real-world study analysed data from 139 patients with R/M SCCHN treated with cetuximab plus chemotherapy at three Indian oncology centres between May 2018 and September 2023. Patients were stratified into CPS <20 and CPS ≥20 groups, receiving either cetuximab with taxane-based or platinum–fluorouracil chemotherapy. Survival was estimated via the Kaplan-Meier method and compared using the log-rank test. Results: The overall objective response rate (ORR) was 80.6%, with similar rates across CPS groups (75.7% vs. 86.2%) and in the oral cavity subgroup. Median progression-free survival and overall survival were 9.0 and 20.0 months, respectively, with no significant differences between CPS groups in either the overall or oral cavity cohorts. Adverse events (AEs), primarily grade 3, were common and included dermatologic and gastrointestinal toxicities, with higher incidence in the oral cavity subgroup and CPS ≥20 group. However, the safety profile remained manageable. Conclusion: Cetuximab-based therapy may be appropriate for symptomatic patients with high tumour burden, regardless of CPS score, showing comparable survival benefits to existing data with manageable safety and no new AEs.

Open article ↗

2026-05-28 | Phase 1 study of induction chemoimmunotherapy (ICI) with cemiplimab in combination with cisplatin and docetaxel (TPI) in locally advanced squaous cell carcinoma of the head and neck (LA SCCHN).

e18085 Background: Despite advances in therapy, overall survival for locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) remains suboptimal, with 5-year survival rates depending on HPV status which indicates a need for additional therapeutic approaches. We sought to improve outcomes by adding immunotherapy to induction chemotherapy with cisplatin and docetaxel (TP). ICI potentially is a less toxic and more efficacious alternative to traditional chemotherapy induction regimens. Methods: In this phase 1, non-randomized study (NCT05376553), patients with previously untreated stage IV LA SCCHN were enrolled into two cohorts. Cohort A received cisplatin (100 mg/m²) and docetaxel (75 mg/m²) on day 1 followed by cemiplimab (350 mg) on day 14 for three cycles; Cohort B received cemiplimab every 3 weeks starting on day −7. Patients then underwent standard-of-care surgery and/or concurrent chemoradiation, followed by adjuvant cemiplimab every 3 weeks for eight cycles. Cemiplimab was combined with TP using a standard 3+3 design without dose escalation. Dose-limiting toxicities attributable to cemiplimab were assessed in cycle 1. Twenty-four patients were enrolled with primary tumors in the oropharynx (15; HPV+ 9), larynx (2), oral cavity (3), nasopharynx (1; HPV+), and hypopharynx (3). Results: 24 eligible patients-initiated therapy and all completed ICI and have completed the study.1 death occurred during follow up period unrelated to study drug or disease. 2 deaths due to progression of disease; 4 patients experienced progression of disease, and 1 patient was lost to follow up. 16/24 (67%) of patients who completed the study remain alive in remission. Of among the 24 patients, that completed ICI the overall response rate (ORR) was 83.33% with 4 partial responses, 14 complete responses, and 6 progressions of disease. The disease control rate is 83.33%, with a relapse rate of 18.18%. 5/5 oral cancer patients underwent resection, 3 had complete pathological response, 1 with 85% pathological tumor necrosis and 1 had a minimal pathological response <10%. There was no dose limiting toxicities The median duration follow-up was 21 months. Conclusions: Induction with ICI with cemiplimab combined with cisplatin and docetaxel was feasible and demonstrated an acceptable safety profile in patients with LA SCCHN, indicating a high ORR and disease control rate. These phase I results support further investigation in larger studies. Clinical trial information: NCT05376553 .

Open article ↗

2026-05-28 | ERBIOTAX (TTCC-2022-02): A phase II, multicenter, randomized study of cetuximab with or without weekly paclitaxel after progression on first-line pembrolizumab plus platinum/5-FU in recurrent or metastatic head and neck squamous cell carcinoma.

TPS6131 Background: Pembrolizumab, with or without platinum–5FU (PF), is the current first-line (1L) standard of care for PD-L1–positive recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). However, no established standard of care exists after progression on immune checkpoint inhibitors (ICI). Emerging evidence suggests that cetuximab administered post-ICI achieves higher objective response rates (ORR) and longer progression-free (PFS) and overall survival (OS) compared with historical second-line (2L) cetuximab outcomes from the pre-ICI era. We hypothesize that 2L treatment with cetuximab +/- paclitaxel may be more effective after ICI failure than previously observed in the pre-ICI era. Methods: This is a multicenter, open-label, randomized, non-comparative, two-arm, investigator-initiated phase 2 trial. Patients will be randomized (2:1) to cetuximab plus paclitaxel (Arm A: ERBITAX) or cetuximab monotherapy (Arm B), administered on Days 1, 8 and 15 of 21-day cycles for 4 cycles, followed in both arms by biweekly cetuximab monotherapy until disease progression, death, unacceptable toxicity, or withdrawal of consent. A total of 65 evaluable patients will be enrolled: 41 in Arm A (H0: ORR 25%, H1: 45%, 80% power, two-sided alpha 0.05) and 24 in Arm B (H0: ORR 10%, H1: 30%, 80% power, two-sided alpha 0.05). The primary endpoint is ORR in each arm. Secondary endpoints include disease control rate (DCR), PFS, OS, health-related quality of life (EORTC QLQ-C30, EORTC QLQ-H&N35 and EuroQol EQ-5D) and safety. Baseline tumor tissue (all patients) and on-treatment samples (between cycles 2-5 in 50% of patients; optionally at progression), as well as serial plasma samples will be collected for translational exploratory studies. Patients must have histologically confirmed SCCHN of oral cavity, oropharynx (HPV-positive or HPV-negative), hypopharynx, or larynx, with confirmed progression per RECIST 1.1. on or after 1L pembro + PF. The study started enrollment in June 2025, with 7 patients enrolled by December 23, 2025. The total accrual period is 18 months. Clinical trial identifiers: NCT06856213; EUDRACT 2024-514953-31-00. Trial supported by Merck, S.L.U., Madrid, Spain, an affiliate of Merck KGaA, Darmstadt, Germany, providing study medication and financial support. Clinical trial information: NCT06856213 .

Open article ↗

2026-05-28 | NRG-HN015: A phase II randomized trial of neoadjuvant chemotherapy or chemo-immunotherapy in patients with recurrent/persistent PD-L1–positive squamous cell carcinoma of the head and neck undergoing salvage surgery.

TPS6128 Background: Treatment for locoregionally recurrent squamous cell carcinoma of the head and neck (SCCHN) remains a challenge. 30-40% of patients treated with definitive-intent therapy will recur, the majority locoregionally (Ang 2010, Galloway 2016, Tan 2010). Despite improvements in the effectiveness of palliative systemic therapy over the last decade (Vermorken 2008), salvage surgery (SS) remains the modality of choice to achieve cure in patients with locally recurrent disease particularly in patients who have previously received radiation. Thus, there is a pressing need to improve the therapeutic ratio by increasing the benefit of SS and improving oncologic outcomes. One promising means would be early introduction of systemic therapy with or without immune checkpoint inhibition for patients who are candidates for SS. NRG-HN015 proposes to investigate the effect on event-free survival (EFS) of pre-operative chemotherapy or chemo-immunotherapy in comparison to the standard SS approach. Methods: NRG-HN015 (NEOPOLIS) is a randomized, multicenter, controlled, 3-arm, superiority phase II study of neoadjuvant chemotherapy or chemo-immunotherapy in patients with recurrent/persistent PD-L1 enriched SCCHN who have planned SS. The primary objective is to compare investigator-assessed EFS of patients treated with neoadjuvant chemotherapy or chemo-immunotherapy prior to SS versus SS alone. The primary hypothesis is that neoadjuvant chemotherapy or chemo-immunotherapy added to SS will improve EFS. Enrolled patients will be randomized 1:1:1 to receive SS (Arm 1 - control), chemotherapy + SS (Arm 2), or chemo-immunotherapy + SS (Arm 3). Prior to randomization, patients will be stratified by primary tumor site (Oropharynx or oral cavity vs. larynx or hypopharynx, stage (rT4a or rN3a vs. other), and prior use of iPD1/PDL1 inhibitors in the definitive setting. Patients must have locally recurrent or persistent SCCHN arising within the oral cavity, oropharynx, larynx, or hypopharynx and are deemed candidates for salvage surgery. P16-positive oropharynx patients with T2, T3, T4, N0, N1, N2 and all other patients with T2, T3, T4a, N0, N1, N2a, N2b, N2c, N3a are eligible. Patients must have PDL1-positive and measurable disease, with no major vascular involvement (>180° involvement of the common carotid or internal carotid artery), jugular foramen involvement, or prevertebral, paraspinous muscle involvement precluding a curative resection. Patients who are candidates for salvage laryngectomy to treat recurrent laryngeal cancer and who are having SS for curative intent are eligible. The trial is opened to enrollment. Clinical trial information: NCT071953734 .

Open article ↗

2026-05-28 | A multicenter, randomized, double-blind, phase 2/3 study of ficerafusp alfa (BCA101) or placebo in combination with pembrolizumab for first-line treatment of HPV-negative, PD-L1–positive, recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): FORTIFI-HN01.

TPS6129 Background: HPV-negative HNSCC is an aggressive disease characterized by high rates of recurrence, metastasis, and resistance to standard treatments. Most HPV-negative HNSCC tumors overexpress tumorigenic factors EGFR and TGF-β. In a phase 1/1b trial (NCT04429542), ficerafusp alfa demonstrated promising efficacy and a manageable safety profile in first-line R/M HNSCC. FORTIFI-HN01 (NCT06788990) is an ongoing randomized, double-blind, placebo-controlled, phase 2/3 trial designed to assess the efficacy and safety of ficerafusp alfa combined with pembrolizumab vs placebo plus pembrolizumab in patients with PD-L1-positive first-line R/M HPV-negative HNSCC. Methods: Eligible patients must have histologically confirmed R/M HNSCC with primary lesions in the oral cavity, larynx, or hypopharynx, or HPV-negative OPSCC confirmed by central laboratory testing. Additional eligibility criteria include no prior systemic therapy for R/M disease, PD-L1-positive tumor (CPS ≥1), measurable disease per RECIST v1.1, and ECOG performance status 0 or 1. The phase 2 objective was to determine the optimal biological dose (OBD) of ficerafusp alfa through an integrated analysis of safety, tolerability, PK, PD, and efficacy. Following OBD determination (1500 mg QW), the trial transitioned seamlessly into the phase 3 portion with 2:1 randomization (ficerafusp alfa:control). Randomization is stratified by PD-L1 CPS (1-19 vs ≥20) and disease extent (local/regional recurrence only, distant metastasis only, or both). Patients receive pembrolizumab (200 mg IV every 3 weeks for up to 35 cycles) and either ficerafusp alfa or placebo IV QW until disease progression or unacceptable toxicity. Tumor imaging occurs every 6 weeks during the first year and every 9 weeks thereafter. The primary endpoints are objective response rate (ORR) per RECIST v1.1 (blind independent committee review) and overall survival. An interim analysis evaluating ORR is planned. Secondary endpoints include safety, duration of response, progression free survival, clinical benefit rate, and patient-reported outcomes. The trial is actively recruiting, with planned enrollment of ~650 subjects. Clinical trial information: NCT06788990 .

Open article ↗

oligonucleotides

2025-05-28 | Randomized phase I trial of adjuvant personalized cancer vaccine TG4050 in resected locally advanced (LA) head and neck squamous cell carcinoma (HNSCC) patients (pts).

6016 Background: Approximately one third of pts with resected LA HNSCC recur. T-cells targeting tumor specific mutations drive anti-tumor immune responses. TG4050 is a viral-based personalized cancer vaccine, encoding up to 30 tumor-specific DNA sequences bearing in-silico predicted class I and class II epitopes. We hypothesized that TG4050 prime an adaptive immune response against tumor antigens and prevent relapse in pts with resected LA HNSCC after treatment with curative intent ( NCT04183166 ). Methods: The multicenter, open label, randomized, 2-arm Phase I trial evaluated TG4050 in LA HNSCC pts achieving complete remission following surgery and adjuvant radiotherapy +/- chemotherapy. Pts were randomized to receive (Arm A) weekly doses of TG4050 for 6 weeks followed by a maintenance period of one dose every 3 weeks for up to 20 doses or no vaccine (Arm B, vaccination at relapse in combination with SOC). Safety, efficacy and immunogenicity were evaluated. In selected pts, exploratory characterization of the T cell response was performed using tetramer staining, bulk and single-cell (sc)TCR sequencing. Results: 33 pts were randomized between January 2021 and April 2023, 17 pts to Arm A and 16 pts to Arm B. Median age was 61 years (26-79 years), tumor location was oral cavity in 24 pts (72.7%), hypopharynx and oropharynx in 4 pts (12.1%), respectively and larynx in one pt (3.0%). TG4050 was safe and well tolerated with only grade 1 or 2 treatment-related adverse events (AEs). The most frequently reported were injection site reactions. After a median follow-up of 28.5 months, all 16 pts receiving TG4050 in Arm A remained disease-free whereas 3 out of 16 pts in Arm B relapsed. Disease Free Survival (DFS) data at 24 months for all patients will be presented. Exploratory qualitative analyses of the neoantigen-specific T cell response by ELISpot were presented previously. In-depth characterization of the neoantigen-specific T cells including clonal expansion by TCR sequencing and longitudinal analysis by tetramer staining will be presented. Conclusions: TG4050 is safe and induces immune responses in pts with resected LA HNSCC. No relapse occurred in the vaccine arm as opposed to 19% in the control arm. With the evolution of the landscape, adjuvant anti-PD1 therapy may become standard in resected LA HNSCC. TG4050 warrants further evaluation in combination with anti-PD1 therapy in phase III trials. Clinical trial information: NCT04183166 .

Open article ↗

2024-03-20 | Unlocking the Therapeutic Potential of LncRNA BLACAT1 in Hypopharynx Squamous Cell Carcinoma.

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 (BLACAT1) expression in HSCC tissues versus adjacent non-tumor tissues. The influence of highly expressed lncRNA BLACAT1 on prognostic survival was assessed. Subsequently, we cultured human pharynx squamous cell carcinoma FaDu cells. After reducing lncRNA BLACAT1 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 BLACAT1. During in vivo experiments, mice received subcutaneous injections of FaDu cells transfected with lncRNA BLACAT1 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 BLACAT1 was screened as one of the most significant genes among the group of differentially expressed lncRNAs. RT-PCR exhibited elevated lncRNA BLACAT1 expression in HSCC tissues when compared to non-tumor tissues (p < 0.001). Furthermore, increased lncRNA BLACAT1 expression correlated with advanced clinical stages, heightened lymphatic invasion, and a poor prognosis. Subsequent in vitro experiments solidified our observations, demonstrating lncRNA BLACAT1's promotion of HSCC cell proliferation (p < 0.05), migration (p < 0.01), and invasion (p < 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 BLACAT1-binding proteins and sh-lncRNA BLACAT1 inhibits STAT3/AKT phosphorylation (p < 0.01) and alters the subcellular distribution of PHB2 and P21 compared with the control group (p < 0.01). Moreover, in vivo experiments showed that lncRNA BLACAT1 inhibition suppresses tumorigenicity in an HSCC xenograft model compared to the control group (p < 0.01). Conclusions: lncRNA BLACAT1 is highly expressed in HSCC tumor tissues and plays a crucial role in the development of HSCC in vitro and in vivo. This increased expression may be caused by STAT3/AKT pathway activation, consequently inhibiting P21 expression through PHB2.

Open article ↗

2023-05-03 | Pharmacological impact of microRNAs in head and neck squamous cell carcinoma: Prevailing insights on molecular pathways, diagnosis, and nanomedicine treatment

Head and neck squamous cell carcinoma is a disease that most commonly produce tumours from the lining of the epithelial cells of the lips, larynx, nasopharynx, mouth, or oro-pharynx. It is one of the most deadly forms of cancer. About one to two percent of all neo-plasm-related deaths are attributed to head and neck squamous cell carcinoma, which is responsible for about six percent of all cancers. MicroRNAs play a critical role in cell proliferation, differentiation, tumorigenesis, stress response, triggering apoptosis, and other physiological process. MicroRNAs regulate gene expression and provide new diagnostic, prognostic, and therapeutic options for head and neck squamous cell carcinoma. In this work, the role of molecular signaling pathways related to head and neck squamous cell carcinoma is emphasized. We also provide an overview of MicroRNA downregulation and overexpression and its role as a diagnostic and prognostic marker in head and neck squamous cell carcinoma. In recent years, MicroRNA nano-based therapies for head and neck squamous cell carcinoma have been explored. In addition, nanotechnology-based alternatives have been discussed as a promising strategy in exploring therapeutic paradigms aimed at improving the efficacy of conventional cytotoxic chemotherapeutic agents against head and neck squamous cell carcinoma and attenuating their cytotoxicity. This article also provides information on ongoing and recently completed clinical trials for therapies based on nanotechnology.

Open article ↗

2018-02-07 | Silencing Ras-Related C3 Botulinum Toxin Substrate 1 Inhibits Growth and Migration of Hypopharyngeal Squamous Cell Carcinoma via the P38 Mitogen-Activated Protein Kinase Signaling Pathway

BACKGROUND Ras-related C3 botulinum toxin substrate 1 (Rac1) is implicated in a variety of cellular functions and is related to tumor growth and metastasis. This study aimed to explore the role of Rac1 in hypopharyngeal squamous cell carcinoma (HSCC). MATERIAL AND METHODS The Rac1 expression in HSCC tissues was determined by quantitative real-time polymerase chain reaction and Western blot analysis. The level of Rac1 in HSCC cells was downregulated by a Rac1-specific shRNA. Then, the growth and metastasis of HSCC cells were assessed in vitro by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, flow cytometry, Hoechst staining, and Transwell assay. Moreover, cells transfected with Rac1 shRNA or negative control were injected subcutaneously into the right axilla of mice, and then the effects of Rac1 silencing on the growth of HSCC were also explored in vivo. Additionally, activation of the P38 mitogen-activated protein kinase (MAPK) signaling pathway was assessed by Western blot. RESULTS Rac1 was highly expressed in HSCC tissues. Silencing Rac1 inhibited the proliferation and cell cycle progress of HSCC cells, and induced their apoptosis. Rac1 silencing also suppressed the migration and invasion of HSCC cells. In vivo study showed that silencing Rac1 suppressed the growth of tumor bodies. Moreover, the P38 MAPK signaling pathway was implicated in the tumor-suppressing effect of Rac1 silencing in vitro and in vivo. CONCLUSIONS Silencing Rac1 suppressed the growth and migration of HSCC through the P38 MAPK signaling pathway. Due to its contribution in HSCC, Rac1 has the potential to become a promising antitumor therapeutic target for HSCC.

Open article ↗

2016-07-29 | CD271 regulates the proliferation and motility of hypopharyngeal cancer cells

CD271 (p75 neurotrophin receptor) plays both positive and negative roles in cancer development, depending on the cell type. We previously reported that CD271 is a marker for tumor initiation and is correlated with a poor prognosis in human hypopharyngeal cancer (HPC). To clarify the role of CD271 in HPC, we established HPC cell lines and knocked down the CD271 expression using siRNA. We found that CD271-knockdown completely suppressed the cells' tumor-forming capability both in vivo and in vitro. CD271-knockdown also induced cell-cycle arrest in G0 and suppressed ERK phosphorylation. While treatment with an ERK inhibitor only partially inhibited cell growth, CDKN1C, which is required for maintenance of quiescence, was strongly upregulated in CD271-depleted HPC cells, and the double knockdown of CD271 and CDKN1C partially rescued the cells from G0 arrest. In addition, either CD271 depletion or the inhibition of CD271-RhoA signaling by TAT-Pep5 diminished the in vitro migration capability of the HPC cells. Collectively, CD271 initiates tumor formation by increasing the cell proliferation capacity through CDKN1C suppression and ERK-signaling activation, and by accelerating the migration signaling pathway in HPC.

Open article ↗

other

2026-05-28 | Empegfilgrastim for primary febrile neutropenia prophylaxis during induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil in head and neck squamous cell carcinoma.

e18030 Background: Induction chemotherapy (CT) with docetaxel, cisplatin, and 5fluorouracil (DCF) before chemoradiotherapy can improve disease control in advanced head and neck squamous cell carcinoma (HNSCC) but is associated with a high risk of severe hematologic toxicity, including febrile neutropenia (FN). Empegfilgrastim is a long-acting granulocyte colony stimulating factor (GCSF) designed to reduce chemotherapy-induced neutropenia and FN. This single-center retrospective study evaluated the incidence of neutropenic complications in HNSCC patients (pts) receiving DCF induction CT with primary FN prophylaxis using empegfilgrastim. Methods: This was a retrospective, single-center cohort of pts with unresectable stage III/IVA hypopharyngeal, laryngeal, or oropharyngeal squamous cell carcinoma treated with 3 cycles of DCF induction CT (docetaxel 75 mg/m² day 1, cisplatin 75 mg/m² day 1, 5fluorouracil 1000 mg/m²/day as a continuous infusion on days 1–4, every 3 weeks), followed by empegfilgrastim 7.5 mg subcutaneously on days 4–8 of each cycle. The primary endpoint was the incidence of grade 3–4 neutropenia (CTCAE v5.0). Secondary endpoints included incidence of FN, nonhematologic adverse events (AEs) grade ≥3, and tumor response after induction CT. Results: A total of 55 pts with unresectable stage III/IVA HNSCC were included: hypopharynx (n=33), larynx (n=8), and oropharynx (n=14). The median age was 60 years (range 39–77); 83% had ECOG performance status 0–1 and 85% were male. Most pts (48/55, 89%) completed all 3 planned DCF cycles. Objective response was assessable in 32 pts, of whom 70% achieved an objective response, including 13 complete responses; the median change in target lesion size was −60% (range −84% to −28%). Grade 3–4 neutropenia occurred in 6 pts (11%), and FN in 4 pts (7.3%). The incidence of any nonhematologic AE grade ≥3 was 3/55 (5%). Conclusions: Primary prophylaxis with empegfilgrastim during DCF induction CT was associated with a relatively low incidence of grade 3–4 neutropenia and FN in pts with advanced HNSCC, while allowing the majority to complete planned treatment. Further analyses are planned to compare the efficacy and safety of empegfilgrastim administration on day 2 versus day 3 of the DCF regimen.

Open article ↗

2025-05-28 | VERSATILE-003: A phase 3, randomized, open-label trial of PDS0101 and pembrolizumab compared with pembrolizumab for first-line treatment of patients with HPV16-positive recurrent/metastatic head and neck squamous cell carcinoma.

TPS6111 Background: Human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) has surpassed cervical cancer as the most common HPV-related cancer in the US, with the majority being caused by HPV16. Persistent expression of HPV16 oncoproteins E6 and E7 by host genome may promote HNSCC. HPV16-positive HNSCC may be associated with poor clinical outcomes in the recurrent/metastatic (R/M) setting. PDS0101 (Versamune HPV) is an HPV16-immunotherapy that generates a potent, targeted T cell attack against HPV16 E6 & E7. In a Phase 2 study, PDS0101 plus pembrolizumab has shown encouraging safety and survival benefit in patients with HPV16-positive R/M HNSCC. (Weiss J et al. ESMO 2024. Poster 879P. NCT04260126). Methods: VERSATILE-003 is a global Phase 3, randomized, controlled, open-label study evaluating PDS0101 plus pembrolizumab vs. pembrolizumab in patients with HPV16-positive R/M HNSCC with PD-L1 positive disease (CPS ≥1). Key eligibility criteria include age ≥18-years-old, histologically- or cytologically-confirmed diagnosis of R/M HNSCC with primary tumor location of oropharynx, oral cavity, hypopharynx, or larynx and no prior systemic anticancer treatment in the R/M setting, HPV16 tumor positivity (centrally tested), PD-L1 positivity defined as CPS ≥ 1 using FDA-approved PD-L1 IHC 22C3 pharmDx kit, and measurable disease based on RECIST 1.1 confirmed by blinded independent central review (BICR). Patients will be randomized 2:1 to receive pembrolizumab 200 mg IV Q3W with PDS0101 1 mL SC administered concurrently during Cycles 1, 2, 3, 4, and 12 (investigational arm), or pembrolizumab 200 mg IV Q3W alone (control arm). The primary objective is to compare overall survival (OS) between the investigational and control arms. Secondary objectives include objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and progression-free survival (PFS) using RECIST 1.1 and assessed by BICR. Exploratory objectives include tumor response assessed by investigator and by irRECIST, PFS2, quality of life as assessed by EQ-5D, QLQ-C30, and QLQ H&N35, and assessment of ctHPVDNA. Updated enrollment data will be provided. Clinical trial information: NCT06790966 .

Open article ↗

2012-04-05 | Analysis and results of Ku and XRCC4 expression in hypopharyngeal cancer tissues treated with chemoradiotherapy

DNA double-strand break (DSB) is one of the most serious forms of damage induced by ionizing irradiation. Non-homologous end-joining (NHEJ) is a key mechanism of DNA DSB repair. The immunohistochemical analysis of proteins involved in NHEJ may have potential as a predictive assay for tumor radiosensitivity. We examined the correlation between the expression of proteins involved in DNA DSB in biopsy specimens and the results of chemoradiotherapy in hypopharyngeal cancers. Fifty-seven patients with previously untreated squamous cell carcinoma of the hypopharynx were treated between March 2002 and December 2009. Most patients (75%) had stage III or IV disease. The chemotherapy consisted of cisplatin plus 5FU or S-1. A tumor dose of 50 Gy was usually administered to the primary tumor and regional lymph nodes. Doses of 10-20 Gy were usually added to the primary tumor with reduced fields after 50 Gy. The 5-year disease-free survival rate was 100% for patients in stage I, 90% in stage II, 64% in stage III and 50% in stage IV. In stages I-III, patients with a lower expression of Ku70 or XRCC4 tended to have better locoregional control. These results indicated that a lower expression of Ku70 or XRCC4 may be correlated with higher radiosensitivity. Two patients had distant metastasis alone, of which one had 0% expression of Ku70 and the other had 0% expression of Ku86. The absence of Ku70 or Ku86 expression indicates low DNA-PK activity. Low DNA-PK activity due to a low expression of Ku may result in the genetic alteration of cancer cells, leading to a higher tendency of distant metastasis. This finding suggests that proteins involved in NHEJ may have an impact on the treatment results of chemoradiotherapy in hypopharyngeal cancer.

Open article ↗

2001-01-01 | The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients

The effect of an adjuvant mistletoe extract treatment was tested in a prospective, randomised controlled clinical trial involving 477 patients with head and neck squamous cell carcinoma. The patients were stratified into two treatment groups that underwent surgery or surgery followed by radiotherapy and both groups were randomised for additional treatment with mistletoe extract. Patients treated with a mistletoe lectin-1 (ML-1) standardised mistletoe preparation had no lower risk of local/locoregional recurrences, distant metastases or second primaries. In the main analysis based on 202 patients treated with surgery and 275 patients treated with surgery and radiotherapy the adjusted hazard ratio for the disease-free survival (DFS) was 0.959 (95% confidence interval (CI) 0.725–1.268). The 5-year survival rates of patients from the mistletoe group were no better than the survival rates of patients from the control group. Furthermore, no significant changes in the cellular immune reaction or in quality of life could be detected. We conclude that the used mistletoe preparation has no indication in the adjuvant treatment of patients with head and neck cancer.

Open article ↗