ABSTRACT
Transparent and precise endpoint definitions are a crucial aspect of clinical trial conduct and reporting, and are used to communicate the benefit of an intervention. Previous studies have identified inconsistencies in endpoint definitions across oncological clinical trials. Here, the Head and Neck Cancer International Group assessed endpoint definitions from phase 3 trials or trials considered practice-changing for patients with recurrent or metastatic mucosal head and neck squamous cell carcinoma, published between 2008 and 2021. We identify considerable and global heterogeneity in endpoint definitions, which undermines the interpretation of results and development of future studies. We show how fundamental components of even incontrovertible endpoints such as overall survival vary widely, highlighting an urgent need for increased rigour in reporting and harmonisation of endpoints.
Subject(s)
Consensus , Endpoint Determination , Head and Neck Neoplasms , Neoplasm Recurrence, Local , Squamous Cell Carcinoma of Head and Neck , Humans , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/mortality , Squamous Cell Carcinoma of Head and Neck/secondary , Squamous Cell Carcinoma of Head and Neck/therapy , Neoplasm Recurrence, Local/pathology , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/therapy , Endpoint Determination/standards , Clinical Trials, Phase III as Topic , Neoplasm MetastasisABSTRACT
Robust time-to-event endpoint definitions are crucial for the assessment of treatment effect and the clinical value of trial interventions. Here, the Head and Neck Cancer International Group investigated endpoint use in phase 3 trials and trials considered potentially practice-changing published between 2008 and 2021 in the curative-intent setting for patients with mucosal head and neck squamous cell carcinoma. Of the 92 trials reviewed, we show that all core components of endpoint reporting were heterogeneous, including definitions of common terms, such as overall survival and progression-free survival. Our report highlights the urgent need for harmonisation of fundamental components of clinical trial endpoints and the engagement of all stakeholders to ensure the transparent reporting of endpoint details.
Subject(s)
Consensus , Endpoint Determination , Head and Neck Neoplasms , Squamous Cell Carcinoma of Head and Neck , Humans , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/therapy , Squamous Cell Carcinoma of Head and Neck/mortality , Head and Neck Neoplasms/therapy , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/mortality , Endpoint Determination/standards , Clinical Trials, Phase III as Topic , Progression-Free SurvivalABSTRACT
BACKGROUND: The health-care industry is a substantial contributor to global greenhouse gas emissions, yet the specific environmental impact of radiotherapy, a cornerstone of cancer treatment, remains under-explored. We aimed to quantify the emissions associated with the delivery of radiotherapy in the USA and propose a framework for reducing the environmental impact of oncology care. METHODS: In this multi-institutional retrospective analysis and simulation study, we conducted a lifecycle assessment of external beam radiotherapy (EBRT) for ten anatomical disease sites, adhering to the International Organization for Standardization's standards ISO 14040 and ISO 14044. We analysed retrospective data from Jan 1, 2017, to Oct 1, 2023, encompassing patient and staff travel, medical supplies, and equipment and building energy use associated with the use of EBRT at four academic institutions in the USA. The primary objective was to measure the environmental impacts across ten categories: greenhouse gases (expressed as kg of carbon dioxide equivalents [CO2e]), ozone depletion, smog formation, acidification, eutrophication, carcinogenic and non-carcinogenic potential, respiratory effects, fossil fuel depletion, and ecotoxicity. Human health effects secondary to these environmental impacts were also estimated as disability-adjusted life years. We also assessed the potential benefits of hypofractionated regimens for breast and genitourinary (ie, prostate and bladder) cancers on US greenhouse gas emissions using an analytic model based on the 2014 US National Cancer Database for fractionation patterns and patient commute distances. FINDINGS: We estimated that the mean greenhouse gas emissions associated with a standard 25-fraction EBRT course were 4310 kg CO2e (SD 2910), which corresponded to 0·0035 disability-adjusted life years per treatment course. Transit and building energy usage accounted for 25·73% (1110 kg CO2e) and 73·95% of (3190 kg CO2e) of total greenhouse gas emissions, respectively, whereas supplies contributed only 0·32% (14 kg CO2e). Across the other environmental impact categories, most of the environmental impact also stemmed from patient transit and energy use within facilities, with little environmental impact contributed by supplies used. Hypofractionated treatment simulations suggested a substantial reduction in greenhouse gas emissions-by up to 42% for breast and 77% for genitourinary cancer-and environmental impacts more broadly. INTERPRETATION: This comprehensive lifecycle assessment of EBRT delineates the environmental and secondary health impacts of radiotherapy, and underscores the urgent need for sustainable practices in oncology. The findings serve as a reference for future decarbonisation efforts in cancer care and show the potential environmental benefits of modifying treatment protocols (when clinical equipoise exists). They also highlight strategic opportunities to mitigate the ecological footprint in an era of escalating climate change and increasing cancer prevalence. FUNDING: Mount Zion Health Fund.
Subject(s)
Neoplasms , Humans , Retrospective Studies , Neoplasms/radiotherapy , United States , Greenhouse Gases/adverse effects , Greenhouse Gases/analysis , Radiotherapy/adverse effects , Environment , Computer SimulationABSTRACT
Detection of extranodal extension on histopathology in surgically treated head and neck squamous cell carcinoma indicates poor prognosis. However, there is no consensus on the diagnostic criteria, interpretation, and reporting of histology detected extranodal extension, which has contributed to conflicting evidence in the literature, and likely clinical inconsistency. The Head and Neck Cancer International Group conducted a three-round modified Delphi process with a group of 19 international pathology experts representing 15 national clinical research groups to generate consensus recommendations for histology detected extranodal extension diagnostic criteria. The expert panel strongly agreed on terminology and diagnostic features for histology detected extranodal extension and soft tissue metastasis. Moreover, the panel reached consensus on reporting of histology detected extranodal extension and on nodal sampling. These consensus recommendations, endorsed by 19 organisations representing 34 countries, are a crucial development towards standardised diagnosis and reporting of histology detected extranodal extension, and more accurate data collection and analysis.
Subject(s)
Consensus , Delphi Technique , Extranodal Extension , Head and Neck Neoplasms , Humans , Head and Neck Neoplasms/pathology , Extranodal Extension/pathology , Squamous Cell Carcinoma of Head and Neck/pathology , Terminology as TopicABSTRACT
Extranodal extension of tumour on histopathology is known to be a negative prognostic factor in head and neck cancer. Compelling evidence suggests that extranodal extension detected on radiological imaging is also a negative prognostic factor. Furthermore, if imaging detected extranodal extension could be identified reliably before the start of treatment, it could be used to guide treatment selection, as patients might be better managed with non-surgical approaches to avoid the toxicity and cost of trimodality therapy (surgery, chemotherapy, and radiotherapy together). There are many aspects of imaging detected extranodal extension that remain unresolved or are without consensus, such as the criteria to best diagnose them and the associated terminology. The Head and Neck Cancer International Group conducted a five-round modified Delphi process with a group of 18 international radiology experts, representing 14 national clinical research groups. We generated consensus recommendations on the terminology and diagnostic criteria for imaging detected extranodal extension to harmonise clinical practice and research. These recommendations have been endorsed by 19 national and international organisations, representing 34 countries. We propose a new classification system to aid diagnosis, which was supported by most of the participating experts over existing systems, and which will require validation in the future. Additionally, we have created an online educational resource for grading imaging detected extranodal extensions.
Subject(s)
Consensus , Extranodal Extension , Head and Neck Neoplasms , Humans , Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/therapy , Extranodal Extension/diagnostic imaging , Extranodal Extension/pathology , Delphi Technique , Terminology as Topic , PrognosisABSTRACT
INTRODUCTION: The primary objective of this study was to determine whether workplace culture in academic oncology differed by gender, during the COVID-19 pandemic. MATERIALS AND METHODS: We used the Culture Conducive to Women's Academic Success (CCWAS), a validated survey tool, to investigate the academic climate at an NCI-designated Cancer Center. We adapted the CCWAS to be applicable to people of all genders. The full membership of the Cancer Center was surveyed (total faculty = 429). The questions in each of 4 CCWAS domains (equal access to opportunities, work-life balance, freedom from gender bias, and leadership support) were scored using a 5-point Likert scale. Median score and interquartile ranges for each domain were calculated. RESULTS: A total of 168 respondents (men = 58, women = 106, n = 4 not disclosed) submitted survey responses. The response rate was 39% overall and 70% among women faculty. We found significant differences in perceptions of workplace culture by gender, both in responses to individual questions and in the overall score in the following domains: equal access to opportunities, work-life balance, and leader support, and in the total score for the CCWAS. CONCLUSIONS: Our survey is the first of its kind completed during the COVID-19 pandemic at an NCI-designated Cancer Center, in which myriad factors contributed to burnout and workplace challenges. These results point to specific issues that detract from the success of women pursuing careers in academic oncology. Identifying these issues can be used to design and implement solutions to improve workforce culture, mitigate gender bias, and retain faculty.
Subject(s)
Academic Success , COVID-19 , Neoplasms , Humans , Female , Male , Sexism , Pandemics , Faculty, Medical , COVID-19/epidemiology , Neoplasms/epidemiologyABSTRACT
There is a significant unmet need and lack of treatment options for patients with resected, high-risk, cisplatin-ineligible locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). Xevinapant, a first-in-class, potent, oral, small-molecule IAP inhibitor, is thought to restore cancer cell sensitivity to chemotherapy and radiotherapy in clinical and preclinical studies. We describe the design of XRay Vision (NCT05386550), an international, randomized, double-blind, phase III study. Approximately 700 patients with resected, high-risk, cisplatin-ineligible LA SCCHN will be randomized 1:1 to receive 6 cycles of xevinapant or placebo, in combination with radiotherapy for the first 3 cycles. The primary end point is disease-free survival, and secondary end points include overall survival, health-related quality of life, and safety.
Squamous cell carcinoma is the most common form of head and neck cancer (SCCHN) and includes cancers of the lips, mouth, throat, tongue and voice box. It is called 'locally advanced' when the cancer has spread to nearby areas but not to other parts of the body. Few treatment options are available for people with locally advanced SCCHN who have had surgery and are unable to receive a type of chemotherapy called cisplatin. Xevinapant is being developed as a possible new type of cancer treatment. It is a liquid that is taken by mouth or given through a feeding tube. Adding xevinapant to the standard treatment called radiotherapy aims to make radiotherapy more effective against the cancer. Researchers have started a large, international, phase III study called XRay Vision to see if adding xevinapant to radiotherapy can help stop the cancer from coming back after surgery and help people live longer. Clinical Trial Registration: NCT05386550 (ClinicalTrials.gov).
Subject(s)
Antineoplastic Agents , Carcinoma, Squamous Cell , Head and Neck Neoplasms , Humans , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin , Head and Neck Neoplasms/drug therapy , Quality of Life , Randomized Controlled Trials as Topic , Squamous Cell Carcinoma of Head and Neck/drug therapy , X-Rays , Double-Blind Method , Clinical Trials, Phase III as TopicABSTRACT
BACKGROUND: Anaplastic thyroid cancer is a rare and aggressive cancer with no standard radiotherapy-based local treatment. Based on data suggesting synergy between pazopanib and paclitaxel in anaplastic thyroid cancer, NRG Oncology did a double-blind, placebo-controlled, randomised phase 2 clinical trial comparing concurrent paclitaxel and intensity-modulated radiotherapy (IMRT) with the addition of pazopanib or placebo with the aim of improving overall survival in this patient population. METHODS: Eligible patients were aged 18 years or older with a pathological diagnosis of anaplastic thyroid cancer, any TNM stage, Zubrod performance status of 0-2, no recent haemoptysis or bleeding, and no brain metastases. Patients were enrolled from 34 centres in the USA. Initially, a run-in was done to establish safety. In the randomised phase 2 trial, patients in the experimental group (pazopanib) received 2-3 weeks of weekly paclitaxel (80 mg/m2) intravenously and daily pazopanib suspension 400 mg orally followed by concurrent weekly paclitaxel (50 mg/m2), daily pazopanib (300 mg), and IMRT 66 Gy given in 33 daily fractions (2 Gy fractions). In the control group (placebo), pazopanib was replaced by matching placebo. Patients were randomly assigned (1:1) to the two treatment groups by permuted block randomisation by NRG Oncology with stratification by metastatic disease. All investigators, patients, and funders of the study were masked to group allocation. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered with Clinicaltrials.gov, NCT01236547, and is complete. FINDINGS: The safety run-showed the final dosing regimen to be safe based on two out of nine participants having adverse events of predefined concern. Between June 23, 2014, and Dec 30, 2016, 89 patients were enrolled to the phase 2 trial, of whom 71 were eligible (36 in the pazopanib group and 35 in the placebo group; 34 [48%] males and 37 [52%] females). At the final analysis (data cutoff March 9, 2020), with a median follow-up of 2·9 years (IQR 0·002-4·0), 61 patients had died. Overall survival was not significantly improved with pazopanib versus placebo, with a median overall survival of 5·7 months (95% CI 4·0-12·8) in the pazopanib group versus 7·3 months (4·3-10·6) in the placebo group (hazard ratio 0·86, 95% CI 0·52-1·43; one-sided log-rank p=0·28). 1-year overall survival was 37·1% (95% CI 21·1-53·2) in the pazopanib group and 29·0% (13·2-44·8) in the placebo group. The incidence of grade 3-5 adverse events did not differ significantly between the treatment groups (pazopanib 88·9% [32 of 36 patients] and placebo 85·3% [29 of 34 patients]; p=0·73). The most common clinically significant grade 3-4 adverse events in the 70 eligible treated patients (36 in the pazopanib group and 34 in the placebo group) were dysphagia (13 [36%] vs 10 [29%]), radiation dermatitis (8 [22%] vs 13 [38%]), increased alanine aminotransferase (12 [33%] vs none), increased aspartate aminotransferase (eight [22%] vs none), and oral mucositis (five [14%] vs eight [24%]). Treatment-related serious adverse events were reported for 16 (44%) patients on pazopanib and 12 (35%) patients on placebo. The most common serious adverse events were dehydration and thromboembolic event (three [8%] each) in patients on pazopanib and oral mucositis (three [8%]) in those on placebo. There was one treatment-related death in each group (sepsis in the pazopanib group and pneumonitis in the placebo group). INTERPRETATION: To our knowledge, this study is the largest randomised anaplastic thyroid cancer study that has completed accrual showing feasibility in a multicenter NCI National Clinical Trials Network setting. Although no significant improvement in overall survival was recorded in the pazopanib group, the treatment combination was shown to be feasible and safe, and hypothesis-generating data that might warrant further investigation were generated. FUNDING: National Cancer Institute and Novartis.
Subject(s)
Chemoradiotherapy , Thyroid Carcinoma, Anaplastic , Thyroid Neoplasms , Female , Humans , Male , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Double-Blind Method , Paclitaxel/adverse effects , Thyroid Carcinoma, Anaplastic/drug therapy , Thyroid Carcinoma, Anaplastic/therapy , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/radiotherapyABSTRACT
OBJECTIVES: To compare post-treatment neck and shoulder function between human papillomavirus-associated oropharynx squamous cell carcinoma (HPV + OPSCC) treatments. DESIGN: Prospective, repeated-measures study. SETTING: Tertiary care center. PARTICIPANTS: Treatment-naïve patients with American Joint Committee on Cancer eighth edition stage T0-3/N0-2 HPV+OPSCC. MAIN OUTCOME MEASURES: Patients completed the Neck Dissection Impairment Index (NDII) pre-treatment and 3-months and 1-year post-treatment. The NDII assesses 10 neck and shoulder functions scored 0-5 (total score 0-100), with higher scores suggesting better function. RESULTS: A total of 106 patients underwent: surgery alone (SA, n = 46, 43%), surgery with adjuvant radiation ± chemotherapy (S + a[C]XRT, n = 18, 17%), or definitive radiation ± chemotherapy (d[C]XRT, n = 42, 40%). cTN classification and pre-treatment NDII scores did not differ between groups. SA patients reported worsened 3-month post-treatment versus pre-treatment self-care (4.6 vs. 5.0), lifting light (4.6 vs. 5.0) and heavy (4.2 vs. 4.8) objects, overhead reach (4.5 vs. 4.9), activity (4.5 vs. 4.9), socialization (4.7 vs. 4.9), recreation (4.6 vs. 4.9), and overall score (86.8 vs. 95.3) (all p < 0.05). One-year post-treatment scores (n = 34) were no different than pre-treatment in all domains. S + a[C]XRT patients reported worsened 3-month versus pre-treatment stiffness (4.0 vs. 4.8), lifting heavy objects (3.8 vs. 4.9), overhead reach (4.2 vs. 4.9), socialization (4.6 vs. 5.0), recreation (4.4 vs. 4.9) and overall score (82.4 vs. 96.0) (all p < 0.05). One-year post-treatment scores (n = 13) were no different than pre-treatment in all domains. d[C]XRT patients reported worsened 3-month versus pre-treatment difficulty lifting heavy objects (4.3 vs. 4.7) and recreation (4.3 vs. 4.7). One-year posttreatment scores (n = 21) were no different than pre-treatment in all domains. CONCLUSION: HPV + OPSCC patients may experience mild shoulder/neck dysfunction 3 months after treatment that usually resolves by 1 year, independent of treatment modality.
ABSTRACT
Head and neck cancer is the seventh most common type of cancer worldwide and comprise of a diverse group of tumours affecting the upper aerodigestive tract. Although many different histologies exist, the most common is squamous cell carcinoma. Predominant risk factors include tobacco use, alcohol abuse, and oncogenic viruses, including human papillomavirus and Epstein-Barr virus. Head and neck malignancies remain challenging to treat, requiring a multidisciplinary approach, with surgery, radiotherapy, and systemic therapy serving as key components of the treatment of locally advanced disease. Although many treatment principles overlap, treatment is generally site-specific and histology-specific. This Seminar outlines the current understanding of head and neck cancer and focuses on treatment principles, while also discussing future directions to improve the outcomes of patients with these malignancies.
Subject(s)
Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/therapy , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/virology , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/virology , Head and Neck Neoplasms/virology , Herpesvirus 4, Human , Humans , Papillomaviridae , Papillomavirus Infections/complications , Papillomavirus Infections/virologyABSTRACT
The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses. Occult primary cancer, salivary gland cancer, and mucosal melanoma (MM) are also addressed. The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's most recent recommendations regarding management of HPV-positive oropharynx cancer and ongoing research in this area.
Subject(s)
Head and Neck Neoplasms , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/therapy , HumansABSTRACT
Background: Several reports have suggested that radiotherapy after reconstructive surgery for head and neck cancer (HNC), could have deleterious effects on the flaps with respect to functional outcomes. To predict and prevent toxicities, flap delineation should be accurate and reproducible. The objective of the present study was to evaluate the interobserver variability of frequent types of flaps used in HNC, based on the recent GORTEC atlas.Materials and methods: Each member of an international working group (WG) consisting of 14 experts delineated the flaps on a CT set from six patients. Each patient had one of the five most commonly used flaps in HNC: a regional pedicled pectoralis major myocutaneous flap, a local pedicled rotational soft tissue facial artery musculo-mucosal (FAMM) (2 patients), a fasciocutaneous radial forearm free flap, a soft tissue anterolateral thigh (ALT) free flap, or a fibular free flap. The WG's contours were compared to a reference contour, validated by a surgeon and a radiologist specializing in HNC. Contours were considered as reproducible if the median Dice Similarity Coefficient (DSC) was > 0.7.Results: The median volumes of the six flaps delineated by the WG were close to the reference contour value, with approximately 50 cc for the pectoral, fibula, and ALT flaps, 20 cc for the radial forearm, and up to 10 cc for the FAMM. The volumetric ratio was thus close to the optimal value of 100% for all flaps. The median DSC obtained by the WG compared to the reference for the pectoralis flap, the FAMM, the radial forearm flap, ALT flap, and the fibular flap were 0.82, 0.40, 0.76, 0.81, and 0.76, respectively.Conclusions: This study showed that the delineation of four main flaps used for HNC was reproducible. The delineation of the FAMM, however, requires close cooperation between radiologist, surgeon and radiation oncologist because of the poor visibility of this flap on CT and its small size.
Subject(s)
Carcinoma , Free Tissue Flaps , Head and Neck Neoplasms , Plastic Surgery Procedures , Head and Neck Neoplasms/surgery , Humans , Melanoma , Plastic Surgery Procedures/methods , Reproducibility of Results , Skin Neoplasms , Melanoma, Cutaneous MalignantABSTRACT
The oral microbiome is a community of microorganisms, comprised of bacteria, fungi, viruses, archaea, and protozoa, that form a complex ecosystem within the oral cavity. Although minor perturbations in the environment are frequent and compensable, major shifts in the oral microbiome can promote an unbalanced state, known as dysbiosis. Dysbiosis can promote oral diseases, including periodontitis. In addition, oral dysbiosis has been associated with other systemic diseases, including cancer. The objective of this review is to evaluate the epidemiologic evidence linking periodontitis to oral, gastrointestinal, lung, breast, prostate, and uterine cancers, as well as describe new evidence and insights into the role of oral dysbiosis in the etiology and pathogenesis of the cancer types discussed. Finally, we discuss how antimicrobials, antimicrobial peptides, and probiotics may be promising tools to prevent and treat these cancers, targeting both the microbes and associated carcinogenesis processes. These findings represent a novel paradigm in the pathogenesis and treatment of cancer focused on the oral microbiome and antimicrobial-based therapies.
Subject(s)
Anti-Infective Agents , Microbiota , Mouth Neoplasms , Anti-Infective Agents/therapeutic use , Dysbiosis , Humans , Male , Mouth Neoplasms/drug therapyABSTRACT
The speed and scale of the global COVID-19 pandemic has resulted in unprecedented pressures on health services worldwide, requiring new methods of service delivery during the health crisis. In the setting of severe resource constraint and high risk of infection to patients and clinicians, there is an urgent need to identify consensus statements on head and neck surgical oncology practice. We completed a modified Delphi consensus process of three rounds with 40 international experts in head and neck cancer surgical, radiation, and medical oncology, representing 35 international professional societies and national clinical trial groups. Endorsed by 39 societies and professional bodies, these consensus practice recommendations aim to decrease inconsistency of practice, reduce uncertainty in care, and provide reassurance for clinicians worldwide for head and neck surgical oncology in the context of the COVID-19 pandemic and in the setting of acute severe resource constraint and high risk of infection to patients and staff.
Subject(s)
Coronavirus Infections/epidemiology , Head and Neck Neoplasms/surgery , Health Care Rationing , Pneumonia, Viral/epidemiology , Practice Guidelines as Topic , Surgical Oncology/standards , Betacoronavirus , COVID-19 , Consensus , Coronavirus Infections/prevention & control , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/pathology , Humans , International Cooperation , Occupational Health , Pandemics/prevention & control , Patient Safety , Pneumonia, Viral/prevention & control , SARS-CoV-2 , Surgical Oncology/organization & administrationABSTRACT
The addition of chemotherapy to radiation therapy (RT) has been established for decades to improve outcomes in patients with head and neck cancer (HNC). Concurrent chemoradiation increases both local control and overall survival but at the cost of significant toxicity, motivating extensive investigations to optimize the balance of clinical efficacy and adverse effects. This review discusses the rationale and seminal studies underlying the concurrent chemoradiation treatment paradigm in HNC, and describes attempts to better tailor systemic therapy beyond standard-of-care cisplatin, such as the use of alternate cytotoxic agents and nonstandard dosing regimens. Modern efforts to incorporate targeted therapies and immunotherapy are then summarized, particularly for patients unable to receive standard cytotoxic chemotherapy. Finally, mechanisms through which RT and systemic therapy cooperate to improve the therapeutic ratio are discussed, with a focus on the interaction between immunotherapy and RT, a rapidly emerging treatment paradigm. With increasing application of novel diagnostic and therapeutic approaches, determining the optimal concurrent systemic program to maximize RT efficacy will continue to evolve. Identification of patient- and tumor-specific factors will offer a unique opportunity to implement personalized oncologic care.
Subject(s)
Antineoplastic Agents , Carcinoma, Squamous Cell , Head and Neck Neoplasms , Antineoplastic Agents/therapeutic use , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy , Head and Neck Neoplasms/therapy , Humans , ImmunotherapyABSTRACT
Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.
Subject(s)
Head and Neck Neoplasms , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/therapy , Humans , Medical Oncology , Practice Guidelines as TopicABSTRACT
PURPOSE: To compare the outcomes of Sinonasal Mucosal Melanomas (SNMM) treated with endoscopic and open resection. METHODS: A retrospective case review of 20 patients with SNMM treated surgically at UCSF. Kaplan-Meier analyses were calculated to determine outcome differences in endoscopic vs. open resections. RESULTS: From 2005 to 2014, 20 cases of SNMM were confirmed and treated at UCSF. All cases underwent surgical resection, with 10 cases by open resection and 10 cases by endoscopic resection. Using Kaplan-Meier analyses, the open resection group had a 1-year survival of 30% whereas endoscopic resection group was 80% (p = 0.032). Endoscopic resection showed improved survival at all time points after surgery compared to open resection. CONCLUSION: SNMM is a rare and aggressive tumor that is associated with low survival rates. In this small case series, endoscopic resection had improved survival outcomes compared to open resection.
Subject(s)
Endoscopy/mortality , Melanoma/surgery , Nasal Mucosa/surgery , Neoplasm Recurrence, Local/surgery , Paranasal Sinus Neoplasms/surgery , Aged , Aged, 80 and over , Endoscopy/methods , Female , Follow-Up Studies , Humans , Male , Melanoma/pathology , Middle Aged , Nasal Mucosa/pathology , Neoplasm Recurrence, Local/pathology , Paranasal Sinus Neoplasms/pathology , Prognosis , Retrospective Studies , Survival RateABSTRACT
BACKGROUND: Radiation Therapy Oncology Group (RTOG)-0129 recursive partitioning analysis was the basis for risk-based therapeutic intensification trials for oropharyngeal cancer (OPC). To the authors' knowledge, the question of whether RTOG-0129 overall survival (OS) estimates for low-risk, intermediate-risk, and high-risk groups are similar in other data sets or applicable to progression-free survival (PFS) is unknown. Therefore, the authors evaluated whether survival differences between RTOG-0129 risk groups persist at 5 years, are reproducible in an independent clinical trial, and are applicable to PFS, and whether toxicities differ across risk groups. METHODS: Prospective randomized clinical trials were analyzed retrospectively. RTOG-0129 evaluated standard versus accelerated fractionation radiotherapy concurrent with cisplatin. RTOG-0522 compared the combination of cisplatin and accelerated fractionation with or without cetuximab. Patients with OPC with available p16 status and tobacco history were eligible. RESULTS: There was a total of 260 patients and 287 patients, respectively, from RTOG-0129 and RTOG-0522, with median follow-ups for surviving patients of 7.9 years (range, 1.7-9.9 years) and 4.7 years (range, 0.1-7.0 years), respectively. Previous OS differences in RTOG-0129 persisted at 5 years. In RTOG-0522, the 5-year OS rates for the low-risk, intermediate-risk, and high-risk groups were 88.1%, 69.9%, and 45.1%, respectively (P for trend, <.001). The 5-year PFS rates for the same 3 groups were 72.9%, 56.1%, and 42.2%, respectively. In RTOG-0522 among a subgroup of patients considered to be at very good risk (p16-positive disease, smoking history of ≤10 pack-years, and classified with T1-T2 disease with ipsilateral lymph nodes measuring ≤6 cm or T3 disease without contralateral or >6 cm lymph nodes), the 5-year OS and PFS rates were 93.8% and 82.2%, respectively. Overall rates of acute and late toxicities were similar by risk group. CONCLUSIONS: RTOG-0129 risk groups persisted at 5 years and were reproducible in RTOG-0522. However, there was variability in the estimates. These data underscore the importance of long-term follow-up and appropriate patient selection in therapeutic deintensification trials.
Subject(s)
Carcinoma, Squamous Cell/mortality , Chemoradiotherapy/mortality , Clinical Trials as Topic/standards , Oropharyngeal Neoplasms/mortality , Papillomavirus Infections/complications , Patient Selection , Risk Assessment/methods , Adult , Aged , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/virology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Oropharyngeal Neoplasms/pathology , Oropharyngeal Neoplasms/therapy , Oropharyngeal Neoplasms/virology , Papillomaviridae/isolation & purification , Papillomavirus Infections/virology , Prognosis , Prospective Studies , Retrospective Studies , Survival RateABSTRACT
OPINION STATEMENT: Standard-of-care treatment for the majority of patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) is either upfront surgery followed by adjuvant treatment as indicated by intraoperative or pathologic findings or concurrent chemoradiation reserving surgical salvage for non-responsive disease. An attempt at upfront complete resection should be pursued if feasible in patients with oral cavity or paranasal sinus primary tumors. Given multimodality treatment paradigms, patients with locoregionally advanced SCCHN should be managed in a multidisciplinary setting. Modern radiation therapy, whether postoperative or definitive in intent, is based on target delineation guided by high-quality imaging, using an intensity-modulated radiation technique to spare organs at risk. In select groups of low-risk patients, most notably those with HPV-associated oropharyngeal SCC (OPSCC), several treatment deintensification approaches are currently under investigation. Major experimental strategies within this non-surgical organ preservation domain include reductions in the intensity of the chemotherapy or radiation therapy components of the chemoradiation program, use of induction chemotherapy, or imaging-based selection of patients eligible for deintensified radiation-based treatment. Of note, recent efforts to substitute cetuximab for cisplatin in low-risk HPV-associated OPSCC have demonstrated the inferiority of cetuximab to cisplatin in cisplatin-eligible patients, re-confirming cisplatin as the standard systemic therapy of choice in HNSCC. In patients who are not candidates for any type of cisplatin administration, carboplatin-based therapy or cetuximab remain options, and other non-cisplatin therapies are under investigation. Altered fractionation may be considered in patients who are not candidates for any type of systemic therapy. The role of immunotherapy in the management of locoregional SCCHN remains investigational.
Subject(s)
Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/therapy , Organ Preservation , Combined Modality Therapy , Head and Neck Neoplasms/etiology , Humans , Multimodal Imaging/methods , Neoplasm Metastasis , Neoplasm Staging , Papillomavirus Infections/complications , Papillomavirus Infections/virology , Standard of Care , Treatment OutcomeABSTRACT
PURPOSE: This study sought to evaluate the effect of early extractions on the timing of postoperative radiation (PORT) for patients with advanced oral cavity squamous cell carcinoma. MATERIALS AND METHODS: All patients with oral cavity squamous cell carcinoma who required resection, free flap reconstruction, and dental extractions in a 10-year period were retrospectively reviewed. The study included patients who preoperatively had advanced disease that indicated the need for adjuvant radiation as defined by an advanced clinical T category (T3 or T4a) or clinical N category (N2a or above). Multivariate logistic regression models were created to estimate the risk factors for initiation of PORT greater than 6 weeks after surgery. RESULTS: Thirty-four patients were included. Thirteen patients underwent early extractions (before or at the time of surgery). Twenty-one patients underwent extractions after surgery. Extractions included all teeth with periodontal disease within the expected field of radiation. Most patients underwent full-mouth extractions (91.1%). PORT was initiated at greater than 6 weeks in 30.8% of patients in the early cohort, whereas 72.4% of patients in the late group experienced a delay (P = .02). Early extractions were significantly associated with a decreased risk of PORT delay. No increase in operating room time occurred for patients who underwent same-day extractions. CONCLUSIONS: Early involvement of the dental oncology department and oral-maxillofacial surgeons can aid in the timely delivery of care for patients with advanced oral cavity cancer.