Recurrent Head And Neck Cancer Research Articles

Spatial resolution of the head and neck cancer tumor microenvironment to identify tumor and stromal features associated with therapy response.

Head and neck cancer (HNC) is the seventh most common cancer globally, resulting in 440 000 deaths per year. While there have been advancements in chemoradiotherapy and surgery, relapse occurs in more than half of HNCs, and these patients have a median survival of 10 months and a 2-year survival of < 20%. Only a subset of patients displays durable benefits from immunotherapies in metastatic and recurrent HNC, making it critical to understand the tumor microenvironment (TME) underpinning therapy responses in HNC. To recognize biological differences within the TME that may be predictive of immunotherapy response, we applied cutting-edge geospatial whole-transcriptome profiling (NanoString GeoMx Digital Spatial Profiler) and spatial proteomics profiling (Akoya PhenoCycler-Fusion) on a tumor microarray consisting of 25 cores from 12 patients that included 4 immunotherapy-unresponsive (8 cores) and 2 immunotherapy-responsive patients (5 cores), as well as 6 immunotherapy naïve patients (12 cores). Through high-plex, regional-based transcriptomic mapping of the tumor and TME, pathways involved with the complement system and hypoxia were identified to be differentially expressed in patients who went on to experience a poor immunotherapy response. Single-cell, targeted proteomic analysis found that immune cell infiltration of the cancer cell mass and interactions of CD8 Tcells with tumor and other immune cells were associated with positive immunotherapy response. The relative abundance of specific tumor phenotypes and their interactions with various immune cells was identified to be different between response groups. This study demonstrates how spatial transcriptomics and proteomics can resolve novel alterations in the TME of HNC that may contribute to therapy sensitivity and resistance.

Head and neck cancer: pathogenesis and targeted therapy.

Head and neck cancer (HNC) is a highly aggressive type of tumor characterized by delayed diagnosis, recurrence, metastasis, relapse, and drug resistance. The occurrence of HNC were associated with smoking, alcohol abuse (or both), human papillomavirus infection, and complex genetic and epigenetic predisposition. Currently, surgery and radiotherapy are the standard treatments for most patients with early-stage HNC. For recurrent or metastatic (R/M) HNC, the first-line treatment is platinum-based chemotherapy combined with the antiepidermal growth factor receptor drug cetuximab, when resurgery and radiation therapy are not an option. However, curing HNC remains challenging, especially in cases with metastasis. In this review, we summarize the pathogenesis of HNC, including genetic and epigenetic changes, abnormal signaling pathways, and immune regulation mechanisms, along with all potential therapeutic strategies such as molecular targeted therapy, immunotherapy, gene therapy, epigenetic modifications, and combination therapies. Recent preclinical and clinical studies that may offer therapeutic strategies for future research on HNC are also discussed. Additionally, new targets and treatment methods, including antibody-drug conjugates, photodynamic therapy, radionuclide therapy, and mRNA vaccines, have shown promising results in clinical trials, offering new prospects for the treatment of HNC.

Local Control, Survival, and Toxicity Outcomes with High-Dose-Rate Peri-Operative Interventional Radiotherapy (Brachytherapy) in Head and Neck Cancers: A Systematic Review.

Background. Peri-operative interventional radiotherapy (POIRT) entails tumor resection, catheter implantation in the same surgery, and irradiation within the peri-operative period. It allows for maximal tumor burden reduction, better tumor bed identification, more flexible implant geometry, highly conformal irradiation, and treatment delay minimization. We reviewed the published local control, survival, toxicity, and quality of life (QOL) outcomes with POIRT for head and neck cancers (HNCs) in primary and re-irradiation settings. Materials and Methods. A systematic search of PubMed, Scopus, Science Direct, and other databases, supplemented by bibliography scanning and hand-searching, yielded 107 titles. Fifteen unique articles were eligible, five of which were merged with more updated studies. Of the ten remaining studies, four reported on primary POIRT, and seven reported on reirradiation POIRT. Given data heterogeneity, only qualitative synthesis was performed. Results. Primary POIRT in early tongue cancer results in 6-year recurrence-free (RFS) and overall survival (OS) of 92% for both; in advanced HNCs, the 9-year RFS and OS rates are 52% and 55%. Grade 1-2 toxicity is very common; grade 3-4 toxicity is rare, but grade 5 toxicity has been reported. POIRT re-irradiation for recurrent HNCs results in 5y RFS and OS rates of 37-55% and 17-50%; better outcomes are achieved with gross total resection (GTR). QOL data are lacking. Conclusions. Primary POIRT is safe and effective in early tongue cancers; its use in other HNC sites, especially in advanced disease, requires careful consideration. Re-irradiation POIRT is most effective and safe when combined with GTR; toxicity is significant and may be limited by careful case selection, implant planning and execution, use of smaller fraction sizes, and adherence to homogeneity constraints. Study Registration Number. PROSPERO Registry Number CRD42024548294.

Dosimetric evaluation of intensity modulated photon versus proton reirradiation of head and neck cancer

BackgroundReirradiation of head and neck cancer (HNC) became more accessible in the last decade, owing to modern irradiation techniques which offer a reduction in treatment related toxicities. The aim of this paper was to comparatively evaluate the dosimetric aspects derived from intensity modulated photon vs. proton treatment planning in reirradiated HNC patients. MethodsSix recurrent HNC patients were enrolled in this retrospective study. For each patient two treatment plans were created: one IMRT/VMAT and one IMPT plan. The prescribed dose for the second irradiation was between 50 and 70 Gy RBE. The study comparatively analyzed the CTV coverage, doses to organs at risk (OARs) and low doses received by the healthy tissue (other than OAR). ResultsSimilar CTV coverage was achieved for photon vs proton plans, with the latter presenting better homogeneity in four cases. Maximum dose to CTV was generally higher for photon plans, with differences ranging from 0.3 to 1.9%. For parotid glands and body, the mean dose was lower for proton plans. A notable reduction of low dose to healthy tissue (other than OARs) could be achieved with protons, with an average of 60% and 64% for D10% and Dmean, respectively. ConclusionThe dosimetric comparison between photon and proton reirradiation of HNC showed a great need for treatment individualization, concluding that protons should be considered for reirradiation on an individual basis.

Real-world evaluation of nivolumab in patients with non-nasopharyngeal recurrent or metastatic head and neck cancer: A retrospective multi-center study by the Turkish Oncology Group (TOG).

e18004 Background: Head and neck cancers (HNCs) represent a significant global health concern due to high morbidity and mortality rates. The prognosis for advanced or recurrent cases remains challenging. Nivolumab obtained approval for recurrent or metastatic HNC based on the Phase III CheckMate 141 trial. This study aimed to evaluate the real-world outcomes of nivolumab in patients with non-nasopharyngeal HNC. Methods: In this multicenter retrospective study, we analyzed 124 patients with recurrent or metastatic non-nasopharyngeal HNC who received nivolumab in the second-line setting and beyond. Data were collected from 22 different cancer centers across Turkey. The effectiveness and safety of the treatment and survival outcomes were evaluated. Results: The median follow-up duration was 7.5 months (3-66.1 months). Overall survival (OS) and progression-free survival (PFS) were determined to be 11.8 and 3.8 months, respectively. Nivolumab exhibited clinical responses, yielding an objective response rate (ORR) of 29.9% and a disease control rate (DCR) of 55.7%. Safety assessments consistently revealed a well-tolerated profile, with no reported instances of treatment discontinuation or mortality attributed to adverse side effects. Notably, several factors, including performance status, neutrophil-to-lymphocyte ratio, tumor location, and p16 positivity, emerged as prognostic indicators significantly associated with OS. Conclusions: Nivolumab is an effective and safe treatment option for patient with recurrent or metastatic non-nasopharyngeal HNC in real-world setting. [Table: see text]

Stereotactic Body Radiotherapy in Recurrent and Oligometastatic Head and Neck Tumours.

The treatment of head and neck cancers (HNCs) encompasses a complex paradigm involving a combination of surgery, radiotherapy, and systemic treatment. Locoregional recurrence is a common cause of treatment failure, and few patients are suitable for salvage surgery. Reirradiation with conventional radiation techniques is challenging due to normal tissue tolerance limits and the risk of significant toxicities. Stereotactic body radiotherapy (SBRT) has emerged as a highly conformal modality that offers the potential for cure while limiting the dose to surrounding tissue. There is also growing research that shows that those with oligometastatic disease can benefit from curative intent local ablative therapies such as SBRT. This review will look at published evidence regarding the use of SBRT in locoregional recurrent and oligometastatic HNCs.

Post-treatment Neutrophil/Lymphocyte Ratio Is a Prognostic Factor in Head and Neck Cancers Treated With Nivolumab.

Inflammation and nutrition-based biomarkers, such as the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), C-reactive protein/albumin ratio (CAR), prognostic nutritional index (PNI), systemic immune inflammation index (SII), and systemic inflammation response index (SIRI), have prognostic value for several types of malignancies. Markers that precisely reflect the prognosis of patients with head and neck cancers (HNCs) treated with immune-checkpoint inhibitors remain unclear. This retrospective study aimed to investigate the prognostic value of hematological markers before and after treatment with nivolumab in patients with recurrent or metastatic HNC (RM-HNC). We evaluated the clinical data of 44 patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab between April 2017 and April 2023 at Shinshu University Hospital. Values of hematological biomarkers (NLR, LMR, PLR, CAR, PNI, SII, and SIRI) were calculated before and 4-6 weeks after nivolumab initiation. Receiver operating characteristic curves were constructed to determine the cutoff values of pre- and post-treatment markers for overall survival (OS) and progression-free survival (PFS). Among all pre- and post-treatment markers, post-treatment NLR showed the highest area under the curve (AUC=0.702). A high post-treatment NLR (cutoff value, 4.01) was associated with a poor OS (p=0.027) and a tendency for shorter PFS (p=0.117). Multivariate analysis showed that a high post-treatment NLR was significantly associated with poor OS (p=0.026). A high post-treatment NLR was associated with poor response to nivolumab in head and neck cancers.

Stereotactic Body Radiation Therapy in Recurrent Head and Neck Cancer: Where Do We Stand?

This review explores the difficulties encountered in the management of head and neck cancer(HNC), with special attention to the challenges presented by locoregional recurrences, which impact a substantial number of patients. While maximal surgical resection remains the gold standard for treatment, surgery is often not feasible due to various factors. In such cases, reirradiation has emerged as a potential strategy, albeit with a heightened risk of severe toxicity. Stereotactic Body Radiation Therapy(SBRT) is introduced as a promising approach for unresectable recurrent HNC. SBRT offers precise radiation doses and shorter treatment durations, making it a potentially optimal treatment modality. Despite the growing interest in SBRT, there is a lack of consensus guidelines for its use in HNC, particularly in India. Nevertheless, recommendations are provided for the benefit of SBRT in reirradiation settings, considering factors like tumour size, dose, and treatment duration. The article highlights the safety and effectiveness of SBRT-based reirradiation with existing evidence. The literature review discusses various studies and their findings, emphasizing the importance of high-dose SBRT for improved overall survival. The article also explores the combination of SBRT with systemic therapy as a potential synergistic approach to enhance patient outcomes. In conclusion, SBRT shows promise as a valuable therapeutic tool for patients with inoperable recurrent HNC, offering acceptable safety. However, further research and well-designed trials are needed to optimize its use and identify the most suitable patient cohorts. Establishing comprehensive working guidelines and a nationwide prospective database will be crucial in advancing this treatment approach.

Head and neck cancers: epidemiology, diagnosis and treatments

Introduction: Head and neck cancers (HNC) affect many subsites in the upper aero-digestive tract. The risk factors include tobacco smoking, chewing betel nut/paan, excessive alcohol consumption, hereditary factors and viruses such as human papillomavirus (HPV) and Epstein–Barr virus (EBV). Early diagnosis, lifestyle changes and HPV vaccination will improve survival. Epidemiology: Globally, recent estimates from GLOBOCAN shows there are 890,000 cases of head and neck cancers annually and 450,000 deaths annually (1). There is an increasing incidence of oral cavity, lip, buccal cancers in the developing world due to higher consumption of tobacco, alcohol and chewing areca nut. There has been an increasing incidence of some HNC due to high-risk strains of human papillomavirus (HPV) (2). Cancers caused by HPV include tonsil cancer, tongue base cancer and unknown primary cancers. The EBV causes nasopharyngeal cancers especially in the Far East. There is a decreasing incidence of some cancers caused by smoking such as laryngeal and hypopharyngeal cancers mainly due to the reduction in smoking rates in some developed countries. Overall, there is a predicted increase in HNC of up to 30% annually by 2030 (2). The HPV-associated cancers affect mainly younger males, who do not necessarily smoke or drink alcohol. The HPV is a strong prognostic factor so patients with HPV positive cancers respond better to treatment as there are less genetic mutations when compared to cancers driven by tobacco smoking. These trends are alarming with socioeconomic impacts. Diagnosis: Symptoms of HNC include difficulty swallowing, persistent sore throat, difficulty breathing, hoarseness, neck lumps, referred pain to the ear, weight loss, and systemic symptoms in advanced disease. A full ENT examination is performed of the oral cavity, oropharynx, neck and ideally flexible nasendoscopy. Ultrasound-guided FNAC or core biopsy of neck lumps are performed. Cross-sectional imaging with CT or MRI scans followed by tumour biopsies either under local or general anaesthetic. Tumour biopsies are assessed using H&amp;E stains, and tests for HPV detection (p. 16 immunohistochemistry, in situ hybridisation or polymerase chain reaction). A PETCT scan is useful for staging cancers, identifying the origin of unknown primary cancers and for surveillance. Treatments: The head and neck cancer multidisciplinary team reviews all investigations and recommends either curative or palliative treatment options that are in every patient’s best interests. Surgery can be open, endoscopic or with the use of a robot. Microvascular reconstruction with flaps is performed as necessary to improve function and quality of life. Oncologic treatments include intensity-modulated radiotherapy (IMRT), which can be combined with chemotherapy. Immunotherapy is a second-line treatment for recurrent HNC currently. Advanced cancers can be treated with palliative intent or best supportive care especially if the patients are frail and have significant comorbidities. There are ongoing clinical trials and research studies exploring better, less-toxic treatments. Multiomics approach and artificial intelligence are exciting developments. Conclusion: There is an increasing incidence of some HNC especially cancers driven by tobacco smoking, alcohol consumption and high-risk human papillomaviruses. Smoking cessation, HPV vaccination, early diagnosis and improvements in treatments are important factors in ensuring good outcomes.

Palliative care interventions for patients with head and neck cancer: protocol for a scoping review

IntroductionA head and neck cancer (HNC) diagnosis significantly impacts a patient’s quality of life (QOL). Palliative care potentially improves their QOL. We will conduct a scoping review to identify existing...

Therapeutic Drug Monitoring of 5-Fluorouracil in Head and Neck Cancer Patients: An Interventional Pilot Study

Abstract Introduction 5-fluorouracil (5-FU) is a crucial agent in treating various types of cancer, particularly recurrent head and neck cancers (HNCs). According to prior studies, individuals who underwent therapeutic drug monitoring (TDM) based 5-FU dosage adjustments showed significantly higher response rates and experienced fewer adverse events compared with those who received the standard 5-FU administration. This study aims to enhance our understanding of the overall clinical outcomes in patients with recurrent HNCs who received 500 mg of 5-FU through a pharmacokinetic (PK) analysis. Objectives Our objectives are to conduct TDM in selected HNC patients and observe individual PK responses, efficacy, tolerability, and drug toxicity. Materials and Methods We enrolled a total of 12 patients with recurrent metastatic HNC, and all of them received a fixed dose of 500 mg with cisplatin in a 21-day cycle. During cycle II or III, we analyzed the blood concentrations and PK parameters of 5-FU using the liquid chromatography and mass spectrometry (LC–MS) technique. Notably, we calculated the Concentration maximum (Cmax), time at which the concentration reaches maxiumum (Tmax), Half life of the drug (T1/2), and area under the curve (AUC) for the 500-mg dose of 5-FU, as the PK data for this particular dose were unavailable, making our study uniquely valuable for assessing efficacy and toxicity. Results Within the study group, 83.33% obtained an average AUC range of 1,000 to 3,000 h/µg/mL. Out of this group, 41.66% showed a partial response, 33.33% experienced disease progression, and 25% remained stable during the therapy. One patient had an AUC below the expected value (832.21 h/µg/mL), while another had an overexposed AUC value (5726.87 h/µg/mL), resulting in a poor clinical outcome. After interpreting the results, suggestions for dosage adjustments were made to the clinician. Conclusion From our interventional study, it is evident that at a flat dose of 500 mg, PK-based individual dosage regimens play a superior role in managing advanced cancer patients with minimal toxicities. This PK analysis showed us clarity on the outcomes of 5-FU at a 500-mg dose.

Two novel stereotactic radiotherapy methods for locally advanced, previously irradiated head and neck cancers patients

To determine the feasibility and utility of conebeam CT-guided stereotactic radiotherapy for locally recurrent, previously irradiated head and neck cancer (HNC) patients on the Halcyon, a ring delivery system (RDS). This research aims to quantify plan quality, treatment delivery accuracy, and overall efficacy by comparing against novel clinical TrueBeam HyperArc method. Ten recurrent HNC patients who were treated at our institution on TrueBeam (6MV-FFF) for 30 to 40 Gy in 3 to 5 fractions with noncoplanar HyperArc plans were re-planned on Halcyon (6MV-FFF). These plans were re-planned with the same Acuros-based dose engine. Additionally, we used site-specific full/partial coplanar VMAT arcs. PTV coverage, mean dose to GTV, maximum dose to organs-at-risk (OAR), beam-on time (BOT), and quality assurance (QA) results were investigated and compared. Halcyon provided highly conformal HNC SRT plans with slightly superior mean PTVD99 coverage (96.7% vs 95.5%, p = 0.071), and slightly lower mean GTV dose (37.8 Gy vs 38.2 Gy, p = 0.241) when compared to the HyperArc plans. Differences in plan conformality and maximum dose to OARs were statistically insignificant. Due to Halcyon's coplanar geometry, D2cm was significantly higher (p = 0.001) but Halcyon did result in a reduced normal brain dose by 1 Gy on average and up to 5.2 Gy in some cases. Halcyon provided similar patient-specific QA pass rates with a 2%/2mm gamma criteria (98.2% vs 98.5%) and independent in-house Monte Carlo second check results (97.7% vs 98.2%), suggesting identical treatment delivery accuracy. Halcyon plans resulted in slightly longer beam-on time (3.16 vs 2.30 minutes, p = 0.010), however door-to-door patient time is expected to be <10 minutes. Compared to clinical TrueBeam HyperArc, Halcyon SRT plans provided similar plan quality and treatment delivery accuracy with a potentially faster overall treatment using fully automated patient setup and verification. Rapid delivery of recurrent HNC SRT may reduce intrafraction motion errors while also improving patient compliance and comfort. To provide high-quality of HNC SRT similar to HyperArc, we recommend Halcyon users consider commissioning this novel method. This method will be useful for remote and underserved patient cohorts including Halcyon-only clinics as well.

Outcomes of Patients Treated with Re-Irradiation for Recurrent Head and Neck Cancer Using Pencil Beam Scanning Proton Therapy

Re-irradiation (re-RT) for recurrent head and neck cancer (HNC) after prior HNC radiation therapy (RT) is clinically challenging given prior radiation of nearby organs at risk (OARs). We describe clinical outcomes and toxicity of pencil beam scanning proton therapy (PBS-PT) for recurrent HNC. We performed a retrospective analysis of recurrent HNC patients treated at a single institution with PBS-PT. Baseline demographic, disease and treatment characteristics were recorded. Local control (LC), locoregional control (LRC), progression free survival (PFS), distant metastasis free survival (DMFS), and overall survival (OS) were estimated using the Kaplan-Meier method. UVA was completed using logistic regression, and MVA was performed using a backward elimination model. We also report acute and late grade 3+ toxicity outcomes, graded per CTCAE v5.0. A total of 89 patients treated with PBS-PT for recurrent HNC between 2016 and 2022 were included. Primary sites included oropharynx (30.0%), oral cavity (22.5%), sinonasal cavity (15.7%), larynx (12.4%) and nasopharynx (6.7%). The most common tumor histology was SCC (73.0%). Median time to re-RT was 47 months. Median dose of PBS-PT was 60 Gy (range: 40-72) with 50.6% receiving BID treatment. Median GTV volume was 30cc (range 4.8-1083cc). 24% of patients received concurrent systemic therapy (46% cytotoxic, 4.5% immunotherapy). Median follow-up after PBS-PT was 8 months (range: 0-71), and median OS was 13 months (95% CI: 9.3-16.7). The median PFS and DMFS were 7 months (95% CI 5.0-9.0) and 9 months (95% CI 5.3-12.7) respectively. The 1- and 2-year LC rates were 80.8% (95% CI: 70.8-90.8) and 66.2% (95% CI: 50.7-81.7). The 1- and 2-year DMFS were 41.0% (95% CI: 30.0-52.0) and 26.3% (95% CI: 15.7-36.9). On UVA and MVA, smaller GTV volume was associated with improved OS (HR 1.002, p = .004), DMFS (HR 1.002, p = 0.004) and PFS (HR 1.002, p = 0.014). In addition, shorter time to re-RT was associated with worse LRC (HR 1.003, p = 0.002), and higher KPS was associated with improved PFS (HR 0.57, p = 0.04). There were 31 acute grade 3 toxicity events (21 patients), the most common being odynophagia (9.0%) followed mucositis (5.6%), dehydration and dermatitis (both 4.5%). One patient had grade 4 toxicity, laryngeal edema requiring intubation 40 days after completion of re-RT. One patient had acute grade 5 toxicity, an oropharyngeal bleed 74 days after completion of re-RT. There were 35 late toxicity events (n = 27), the most common being dysphagia (n = 7, 7.9%). One patient suffered late grade 5 osteoradionecrosis, which resulted in sepsis. PBS-PT for recurrent HNC results in effective disease control and favorable toxicity. Patients with smaller GTV volume appear to have improved OS, PFS and DMFS, and may be better candidates. Those with shorter time to re-RT also have worse LRC. However, distant failure (DF) comprises a major failure pattern, and biomarkers to identify patients at risk for DF may improve clinical decision making.

Toxicity and Dosimetric Analysis of Reirradiation of Head and Neck Cancers with High Dose Rate Brachytherapy

Reirradiation (reRT) of recurrent or second primary head and neck cancers (HNC) after prior curative-intent external beam radiotherapy (EBRT) has historically achieved local control (LC) rates of 40-50% and been associated with high grade toxicity rates estimated at 25-50%. This study evaluated the hypothesis that patients with small reRT target volumes could be selected for high dose rate brachytherapy (HDR-BT) reRT and achieve similar LC without excess toxicity. Included were all patients with HNC squamous cell carcinoma treated with HDR-BT after having previously received curative-intent EBRT for primary HNC from 2000-2021. Patients were selected by a multidisciplinary tumor board to be appropriate candidates for HDR-BT reRT without EBRT generally for definitive or adjuvant treatment of small primary tumors without neck nodal metastases. Univariate analysis was performed using the logistic regression model. Survival outcomes were estimated with the Kaplan Meier method. Twenty-three patients were evaluated. Median follow up time was 19mo. Median age at time of HDR-BT was 64 years. Thirteen patients (57%) were treated for recurrent HNC, of which 7 were in the oral cavity (OC) and 6 were the oropharynx (OPX). Ten patients (43%) were treated for a second primary HNC, of which 5 were in the OC and 5 were in the OPX. Median time from completion of EBRT to HDR-BT was 41 (IQR 14-73) mo. Within their reRT course, 11 patients (48%) were treated with HDR-BT after resection, 9 patients (39%) received concurrent hyperthermia, and 7 patients (30%) received chemotherapy. HDR-BT regimens included 600cGy x5 (N = 11), 600cGy x6 (N = 6), 450cGy x8 (N = 1), 1500cGy x1 (N = 1),1000cGy x1 (N = 1), 500cGy x8 (N = 1), and 700cGy x5 (N = 1). One patient who was treated with two implants received 450cGy x 3 followed by 475cGy x5. A median of 5 brachytherapy catheters were used. Actuarial 2-year LC and overall survival rate was 68% and 62%, respectively. Of the 17 HDR-BT reRT plans available for review, median (IQR) target volume was 15.8 (10.6-34.9) cc. Median (IQR) target V100% was 90.6 (89.4-90.0)%, V150% was 50.5 (49.7-54.4)%, and V200% was 25.4 (23.8-29.0)%. Median (IQR) target D90% was 30.1 (29.8-35.5) Gy, and median D1cc was 116.4 (100.5-171.4) Gy. The mandible dose [median (IQR)] was D2cc:15.1(9.48-18.9) Gy; D1cc:16.9(11.1-21.3) Gy; and D1%:18.8(13.4-22.7) Gy. Nine of the 23 patients (39%) experienced ≥G3 toxicity including fistula, soft tissue necrosis, osteoradionecrosis, ulcer, hemorrhage, and dysphagia requiring a chronic feeding tube. Target D90% was associated with ≥G3 toxicity (p = 0.045). For D90% greater than the median of 30Gy, 45% ≥G3 toxicity was observed. This study suggests that HDR-BT for reRT of small recurrent or second primary HNC can provide similar LC without excess high-grade toxicities as compared to historical outcomes with EBRT reRT. Delivery of equivalent doses higher than 30Gy in 5 fractions should be approached with caution.

Immunotherapy in Head and Neck Cancer: Where Do We Stand?

Head and neck cancer (HNC) comprises a group of malignancies, amongst which squamous cell carcinoma accounts for more than 90% of the cases. HNC has been related to tobacco use, alcohol consumption, human papillomavirus, Epstein-Barr virus, air pollution, and previous local radiotherapy. HNC has been associated with substantial morbidity and mortality. This review aims to summarize the recent findings regarding immunotherapy in HNC. The recent introduction of immunotherapy, with the use of programmed death 1 (PD-1) inhibitors pembrolizumab and nivolumab, which have been FDA approved for the treatment of metastatic or recurrent head and neck squamous cell carcinoma, has changed the field in metastatic or recurrent disease. There are many ongoing trials regarding the use of novel immunotherapeutic agents, such as durvalumab, atezolizumab, avelumab, tremelimumab, and monalizumab. In this review, we focus on the therapeutic potential of novel immunotherapy treatment modalities, such as combinations of newer immune-checkpoint inhibitors; the use of tumor vaccines such as human papillomavirus-targeted vaccines; the potential use of oncolytic viruses; as well as the latest advances regarding adoptive cellular immunotherapy. As novel treatment options are still emerging, a more personalized approach to metastatic or recurrent HNC therapy should be followed. Moreover, the role of the microbiome in immunotherapy, the limitations of immunotherapy, and the various diagnostic, prognostic, and predictive biomarkers based on genetics and the tumor microenvironment are synopsized.

Patterns of recurrence in head and neck squamous cell carcinoma to inform personalized surveillance protocols.

Development of evidence-based post-treatment surveillance guidelines in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is limited by comprehensive documentation of patterns of recurrence and metastatic spread. A retrospective analysis of patients diagnosed with R/M HNSCC at a National Cancer Institute-designated cancer center between 1998- 2019 was performed (n=447). Univariate and multivariate analysis identified patterns of recurrence and predictors of survival. Median overall survival (mOS) improved over time (6.7months in 1998-2007 to 11.8months in 2008-2019, p= .006). Predictors of worse mOS included human papillomavirus (HPV) negativity (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.2-2.6), high neutrophil/lymphocyte ratio (HR, 2.1 [1.4-3.0], disease-free interval (DFI) ≤6months (HR, 1.4 [1.02-2.0]), and poor performance status (Eastern Cooperative Oncology Group, ≥2; HR, 1.91.1-3.4). In this cohort, 50.6% of recurrences occurred within 6months of treatment completion, 72.5% occurred within 1year, and 88.6% occurred within 2years. Metachronous distant metastases were more likely to occur in patients with HPV-positive disease (odds ratio [OR], 2.3 [1.4-4.0]), DFI >6months (OR, 2.4 [1.5-4.0]), and body mass index ≥30 (OR, 2.3 [1.1-4.8]). Oligometastatic disease treated with local ablative therapy was associated with improved survival over polymetastatic disease (HR, 0.36; 95% CI, 0.24-0.55). These data regarding patterns of distant metastasis in HNSCC support the clinical utility of early detection of recurrence. Patterns of recurrence in this population can be used to inform individualized surveillance programs as well as to risk-stratify eligible patients for clinical trials. After treatment for head and neck cancer (HNC), patients are at risk of recurrence at prior sites of disease or at distant sites in the body. This study includes a large group of patients with recurrent or metastatic HNC and examines factors associated with survival outcomes and recurrence patterns. Patients with human papillomavirus (HPV)-positive HNC have good survival outcomes, but if they recur, this may be in distant regions of the body and may occur later than HPV-negative patients. These data argue for personalized follow-up schedules for patients with HNC, perhaps incorporating imaging studies or novel blood tests.

Novel Immunotherapeutic Approaches to Treating HPV-Related Head and Neck Cancer.

Head and neck cancer (HNC) is the seventh most common malignancy, with oropharyngeal squamous cell carcinoma (OPSCC) accounting for a majority of cases in the western world. While HNC accounts for only 5% of all cancers in the United States, the incidence of a subset of OPSCC caused by human papillomavirus (HPV) is increasing rapidly. The treatment for OPSCC is multifaceted, with a recently emerging focus on immunotherapeutic approaches. With the increased incidence of HPV-related OPSCC and the approval of immunotherapy in the management of recurrent and metastatic HNC, there has been rising interest in exploring the role of immunotherapy in the treatment of HPV-related OPSCC specifically. The immune microenvironment in HPV-related disease is distinct from that in HPV-negative OPSCC, which has prompted further research into various immunotherapeutics. This review focuses on HPV-related OPSCC, its immune characteristics, and current challenges and future opportunities for immunotherapeutic applications in this virus-driven cancer.

Impact of cetuximab plus cisplatin alone and cetuximab plus cisplatin and paclitaxel regimen on humanistic outcome in head and neck cancer

BackgroundThe prevalence of head and neck cancer (HNC) is increasing rapidly, and the prognosis is poor in the advance stage. For the patient suffering from advance stage HNC, the improvement in quality of life and decrease mortality remain as the mainstay of treatment. The aim was to assess the change in quality-adjusted life-years (QALYs) in recurrent or metastatic HNC patients receiving cetuximab plus cisplatin and cetuximab plus cisplatin-paclitaxel.MethodsIt was a single-centric prospective-observational study. Patients were divided into two cohorts based on the chemotherapy regimens they were prescribed. Patients in cohort 1 were prescribed with cetuximab and cisplatin and in cohort 2 were prescribed with cetuximab, cisplatin, and paclitaxel. The QALYs were the primary outcome of the study, and it was calculated using EQ-5D-5L instrument. Patients were followed until the completion of the therapy, i.e., six chemotherapy cycles. The statistical analysis was carried out using SPSS for descriptive and inferential analysis.ResultsAmongst 175 patients screened, 100 patients were enrolled which further distributed in cohorts 1 and 2 equally. The mean QALYs were 0.016 and 0.017 at the time of diagnosis, i.e., before initiation of chemotherapy for patients in cohorts 1 and 2, respectively. At every chemotherapy cycle, the QALYs were calculated. After the completion of six chemotherapy cycles, the mean QALYs were 0.029 and 0.032 for patients in cohorts 1 and 2, respectively.ConclusionThe three-drug therapy consisting of cetuximab, cisplatin, and paclitaxel has shown significant improvement in patients’ QALYs compared to two-drug regimens of cetuximab and cisplatin. Thus, if the therapy consisted of three-drug regimen is used instead of two-drug regimen, it will have a positive impact on humanistic outcome in recurrent or metastatic HNC patients.

The role of the speech and language therapist in the rehabilitation of speech, swallowing, voice and trismus in people diagnosed with head and neck cancer.

Head and neck cancer (HNC) and its treatment can have a significant impact on physical and psychosocial wellbeing. A multidisciplinary team (MDT) approach is critical to reduce the potential acute, long-term and late effects of treatment by optimising function at baseline, supporting people during treatment and with rehabilitation post treatment. The key focus for speech and language therapists is to support the holistic needs of people with a focus on speech, swallowing, voice and mouth opening. Effective management is reliant on working with MDT members and interventions are implemented against the background of robust multidimensional baseline evaluation. There have been significant advances in treatment modalities for both primary and recurrent HNC. These include highly conformal radiotherapy modalities, including: image-guided radiotherapy; parotid-sparing and dysphagia-optimised intensity-modulated radiotherapy; and the introduction of intensity-modulated proton therapy, as well as immunotherapy, transoral robotic surgery and surgery with advanced reconstructive techniques. Such treatment advances coupled with a changing patient demographic means that people with HNC are now living longer. However, this is not always without consequences and late treatment effects are a new challenge facing MDTs, requiring high levels of support and rehabilitation.

Intraoperative radiation therapy for locally advanced and recurrent head and neck cancer.

The purpose of the present study was to present a single institution experience with intraoperative radiation therapy (IORT) for patients with head and neck cancer (HNC). The present study included all patients with HNC treated consecutively with IORT at Loyola University Medical Center between January 2014 and December 2018. Charts were reviewed for patient and tumor characteristics, IORT technical details, IORT-induced adverse events and treatment outcomes. The study included 23 eligible patients. Median patient age was 66 years (range, 34-91 years). Tumor sites included the parotid gland (43%), lymph nodes (43%), oral tongue (9%) and ear (4%). A total of 48% of patients received IORT upfront with or without postoperative adjuvant external beam radiation therapy (EBRT), whereas 52% received salvage IORT after local tumor recurrence. The median prescribed IORT dose was 7.5 Gy (range, 5-14 Gy) in a single fraction prescribed to 5 mm depth with flat applicators (median diameter, 5 cm). A total of 92% of patients did not experience wound healing complications. One patient (4%) developed postoperative acute thromboembolic stroke and a second patient (4%) experienced protracted wound healing. At a median follow up of 36 months (range, 2-81 months), overall survival was 52%. In addition, 48% of patients were reported to have no evidence of disease, and although two had died of unrelated causes, 13% of patients were alive with disease and 39% died with the disease. The local-regional recurrence rate was 39% (median time to local recurrence, 11 months; range, 1-34 months), the rate of distant metastasis was 35% (median time to distant metastasis, 16 months; range, 4-40 months), and 21% of patients had both local-regional recurrence and distant metastases. The percentages of local-regional recurrence and distant metastases among patients receiving salvage IORT were 58 and 50% respectively, compared with 18 and 18% respectively in those receiving upfront IORT with or without adjuvant EBRT. In the present single institution retrospective study, it was concluded that IORT for patients with locally advanced and recurrent HNC was a safe treatment modality, with tumor control comparable to historical IORT data. Larger prospective studies are needed to further assess the utility of IORT in the management of locally advanced and recurrent HNC.