Psychosocial consequences of head and neck cancer symptom burden after chemoradiation: a mixed-method study.

PURPOSE: Patients with head and neck cancer (HNC) experience significant symptom burden from combination chemotherapy and radiation (chemoradiation) that affects acute and long-term health-related quality of life (HRQOL). However, psychosocial impacts of HNC symptom burden are not well understood. This study examined psychosocial consequences of treatment-related symptom burden from the perspectives of survivors of HNC and HNC healthcare providers. METHODS: This was a cross-sectional, mixed-method study conducted at an NCI-designated comprehensive cancer center. Participants (N = 33) were survivors of HNC who completed a full course of chemoradiation (n = 20) and HNC healthcare providers (n = 13). Participants completed electronic surveys and semi-structured interviews. RESULTS: Survivors were M = 61 years old (SD = 9) and predominantly male (75%), White (90%), non-Hispanic (100%), and diagnosed with oropharynx cancer (70%). Providers were mostly female (62%), White (46%) or Asian (31%), and non-Hispanic (85%) and included physicians, registered nurses, an advanced practice nurse practitioner, a registered dietician, and a speech-language pathologist. Three qualitative themes emerged: (1) shock, shame, and self-consciousness, (2) diminished relationship satisfaction, and (3) lack of confidence at work. A subset of survivors (20%) reported clinically low social wellbeing, and more than one-third of survivors (35%) reported clinically significant fatigue, depression, anxiety, and cognitive dysfunction. CONCLUSION: Survivors of HNC and HNC providers described how treatment-related symptom burden impacts psychosocial identity processes related to body image, patient-caregiver relationships, and professional work. Results can inform the development of supportive interventions to assist survivors and caregivers with navigating the psychosocial challenges of HNC treatment and survivorship.

Safety outcomes of pembrolizumab with platinum agent chemotherapy combined with 5-fluorouracil or taxane derivative in head and neck cancer.

INTRODUCTION: For patients with metastatic head and neck squamous cell cancer (HNSCC), the outcomes of pembrolizumab in combination with a platinum agent and taxane as first-line therapy remain unknown. The purpose of this study is to characterize the impact of substituting the 5-fluorouracil (5-FU) backbone for a taxane in this chemoimmunotherapy regimen on safety/tolerability and survival outcomes. METHODS: This was an IRB-approved, single-center, retrospective, active comparator, new-user design study in adult patients with HNSCC treated between January 2018 and September 2021. The primary objective was to assess safety and tolerability of pembrolizumab in combination with a platinum agent and taxane against an active comparator arm of pembrolizumab in combination with a platinum agent and 5-FU. Safety and tolerability were evaluated by assessing differences in overall toxicities, with further secondary analysis evaluating differences in hematologic toxicities and pre-defined non-hematologic toxicities. RESULTS: There was no statistical difference demonstrated with the primary endpoint between the cohorts. Reduced toxicity rates were found in the taxane arm for mucositis and creatinine levels. No grade 4 non-hematologic toxicities were reported. Patients receiving 5-FU were more likely to have dose reductions upfront, discontinue treatment due to intolerances and had significantly higher mucositis. CONCLUSIONS: This study helps to characterize the safety profile and activity of pembrolizumab in combination with a platinum agent and taxane derivative in HNSCC patients. Within our study, substitution of 5-FU with a taxane did not show an increased risk of toxicities, worsened survival, or decreased odds of achieving a response. Mucositis and elevated creatinine rates were significantly reduced within the taxane arm.

Smoking Is Related to Worse Cancer-related Symptom Burden.

BACKGROUND: Cigarette smoking is related to greater cancer incidence, worse cancer-related clinical outcomes, and worse patient quality of life. Few studies have evaluated the role of smoking in patients' experiences of cancer-related symptom burden. This study examined relationships between smoking and total symptom burden as well as the incidence of severe symptoms among adult cancer patients. PATIENTS AND METHODS: Patients at Moffitt Cancer Center completed self-report surveys as part of routine cancer care. Symptom burden was evaluated as the sum of individual symptom ratings (total symptom burden) and the number of symptoms rated severe (incidence of severe symptoms). Zero-inflated negative binomial modeling was used to evaluate the relationships between smoking status (ever vs never smoker) and symptom burden outcomes controlling for relevant sociodemographic and clinical covariates and accounting for the proportion of participants reporting no symptom burden. RESULTS: This study included 12 571 cancer patients. More than half reported a history of cigarette smoking (n = 6771, 55%). Relative to never smokers, participants with a smoking history had 15% worse expected total symptom burden (ratio = 1.15, 95% confidence interval [CI] 1.11-1.20, P < .001) and 13% more expected severe symptoms (ratio = 1.13, 95% CI 1.05-1.21, P = .001) above and beyond the effects of relevant sociodemographic and clinical characteristics. CONCLUSION: Results provide support that smoking is associated with worse cancer symptom burden. More research is needed to evaluate how smoking history (ie, current vs former smoker) and smoking cessation influence cancer symptom burden.

Considerations for developing supportive care interventions for survivors of head and neck cancer: A qualitative study.

OBJECTIVE: This study aimed to describe considerations for developing supportive care interventions targeted to head and neck cancer (HNC) survivors. METHODS: One-time semi-structured interviews (N = 33) were conducted with HNC survivors who had recently finished treatment (n = 20) and HNC providers (e.g., physicians, nurses; n = 13). Interviews were transcribed verbatim and coded using inductive applied thematic analysis techniques to identify themes. RESULTS: HNC survivors (75% male; M = 61 years old) and providers (54% physicians; 62% female) were unanimously supportive of developing HNC-specific supportive care interventions. Participants described potential benefits of offering interventions at various points throughout the HNC treatment and survivorship trajectory rather than at a single critical time. Many participants preferred group-based interventions because of the high value of peer-support. Others described how group interventions may not be appropriate for all HNC survivors due to risks for negative social comparisons and exacerbated anxiety. Participants suggested topics that should be addressed in HNC-specific interventions including education about acute and long-term side effects, symptom management, nutritional support, relationship/social role changes, grief/loss, and fear of recurrence. CONCLUSIONS: HNC-specific supportive care interventions are critically needed, as survivors experience persistent symptoms and distinct psychosocial concerns that impact quality of life. Findings from this study can inform the development of supportive care interventions targeted to the unique psychosocial concerns of HNC survivors.

"I have cancer during COVID; that's a special category": a qualitative study of head and neck cancer patient and provider experiences during the COVID-19 pandemic.

PURPOSE: The COVID-19 pandemic has drastically changed cancer care delivery strategies. Patients with locally advanced head and neck cancer (LA-HNC) may be particularly affected by the COVID-19 pandemic, as they often undergo treatments that require daily clinic visits (e.g., radiation therapy). The goal of this study was to characterize the lived experience of LA-HNC patients and their healthcare providers during the COVID-19 pandemic. METHODS: LA-HNC patients who completed a full course of chemotherapy and radiation therapy during the COVID19 pandemic (N = 20) and LA-HNC healthcare providers (N = 13) participated in semi-structured interviews. Interviews were audio-recorded, transcribed verbatim, and analyzed for qualitative themes. RESULTS: The COVID-19 pandemic had a significant impact on patients' overall quality of life and health care. Results were organized in four main themes: (1) increased psychological distress; (2) exacerbated social isolation; (3) added stress in clinic for patients and providers; and (4) delays in health care. CONCLUSIONS: Findings highlight myriad ways LA-HNC patients and providers have been affected by the COVID-19 pandemic. Results can inform the development of supportive interventions to assist LA-HNC in managing COVID-19-related stress and unmet needs related to social isolation and in-clinic support.

Adrenal biopsy, as a diagnostic method, is associated with decreased overall survival in patients with T1/T2 adrenocortical carcinoma: A propensity score-matched analysis.

INTRODUCTION: The standard diagnosis for adrenocortical carcinoma (ACC) is clinical diagnosis (CD) based on radiographic and biochemical studies. Biopsy diagnosis (BD) is seldom required for the suspicion of secondary malignancy. We aim to study the impact of BD in the context of underlying T1/T2 ACC on overall survival (OS) compared with CD. METHODS: National Cancer Database (NCDB) for endocrine malignancies was utilized. Only patients with non-metastatic ACC, whose method of diagnosis and local disease extension were reported, and received a surgical adrenalectomy with curative intent were included. Patients were divided by disease stage into T1/T2, T3, and T4 groups. A propensity score match was applied to those with T1/T2 disease who received CD versus BD and the Kaplan-Meier method was used to compare OS. RESULTS: In total, 4000 patients with ACC were reported in the database, 1410 met selection criteria. Eight hundred and thirty patients had T1/T2, 365 had T3, and 162 had T4 ACC. Of patients with T1/T2 ACC, 742 (89.4%) received CD versus 88 (11.6%) with BD. A propensity score was calculated per a multivariable regression model with 79 patients matched from each group. Exact matching was applied for margin status and adjuvant therapies. Kaplan-Meier analysis showed a significant difference in median OS between CD versus BD patients in the matched data set (103.89 ± 15.65 vs. 54.93 ± 8.22 months; p = 0.001). In all comers, patients with T1/T2 ACC and BD had comparable median OS to that of patients with T3 ACC (52.21 ± 9.69 vs. 36.01 ± 3.33 months; p = 0.446). CONCLUSION: BD in T1/T2 ACC could be associated with disease upstaging and worse OS outcomes.

Emerging Therapies for Radioactive Iodine Refractory Thyroid Cancer.

OPINION STATEMENT: The landscape of treatment options for radioactive iodine refractory thyroid cancer is rapidly changing. While there are no curative options in this setting, tyrosine kinase inhibitors (TKIs) have revolutionized the management of radioiodine refractory disease to help delay progression of metastatic and life-threatening disease. Ongoing development of more selective targeted inhibitors will certainly improve medication tolerability and tumor specificity. In this review, we discuss the epidemiology of radioactive iodine refractory thyroid cancer and examine the definition of radioactive iodine refractory disease and the current systemic therapy options. We then discuss molecularly targeted strategies both approved by the FDA and currently under study in clinical trials. In particular, we examine the data relevant to specific targeted mutations in thyroid cancer. We also discuss novel approaches in development, such as immunotherapy, to the management of radioactive iodine refractory disease.

Transplant-Associated Thrombotic Microangiopathy Is a Multifactorial Disease Unresponsive to Immunosuppressant Withdrawal.

Transplant-associated thrombotic microangiopathy (TA-TMA) after allogeneic hematopoietic cell transplantation (HCT) has not been well characterized in large population studies with clinically adjudicated cases. We performed a retrospective cohort study of adults who underwent allogeneic HCT between 2006 and 2015 to determine the incidence of and risk factors for TA-TMA and to describe its natural history and response to immunosuppressant withdrawal management. Among 2145 patients in this study, 192 developed TA-TMA with a cumulative incidence of 7.6% by 100days post-transplant. Independent pretransplant risk factors included the receipt of a second (or third) allogeneic HCT, HLA-mismatched donor, and myeloablative conditioning with or without total body irradiation; post-transplant risk factors included the antecedent development of acute graft-versus-host disease, diffuse alveolar hemorrhage, bacteremia, invasive aspergillosis, BK viremia, and higher sirolimus trough level. Among TA-TMA patients 27% achieved hematologic resolution and 57% remained alive as of 90days after diagnosis. Antecedent risk factors stratified patients into different survival groups, and immunosuppressant withdrawal alone did not improve patient outcomes. In conclusion, TA-TMA is a heterogenous disease that occurs after allogeneic transplantation. Management with immunosuppressant withdrawal does not impact patient outcomes. Until further evidence becomes available, the management of TA-TMA should focus on the treatment of underlying diseases.

Racial and ethnic disparities in hematologic malignancies.

Racial and ethnic disparities in patients with solid malignancies have been well documented. Less is known about these disparities in patients with hematologic malignancies. With the advent of novel chemotherapeutics and targeted molecular, cellular, and immunologic therapies, it is important to identify differences in care that may lead to disparate outcomes. This review provides a critical appraisal of the empirical research on racial and ethnic disparities in incidence, survival, and outcomes in patients with hematologic malignancies. The review focuses on patients with acute myeloid leukemia, acute lymphocytic leukemia, multiple myeloma, non-Hodgkin lymphoma, Hodgkin lymphoma, myeloproliferative neoplasms, and myelodysplastic syndrome. The review discusses possible causes of racial and ethnic disparities and also considers future directions for studies to help decrease disparities.

Leaving footprints, not scars: a qualitative pilot study of Hispanic mothers' willingness to communicate with dependent children about an advanced cancer diagnosis.

PURPOSE: US Hispanics are more likely to be diagnosed with advanced cancer as parents than their non-Hispanic white counterparts but little is known about Hispanic parents' willingness to discuss a terminal cancer diagnosis with dependent children, potentially resulting in suboptimal child coping. Therefore, we investigated Hispanic mothers' willingness to communicate with dependent children about her actual or hypothetical advanced cancer diagnosis. METHODS: Two focus groups (n = 6 participants) and three one-on-one interviews (n = 3) were conducted in either Spanish or English among adult, Mexican-American mothers with a current cancer diagnosis of any stage residing in US-Mexico border communities. Participants reported their perceived concerns, parenting challenges, and openness to discussing an incurable cancer diagnosis with a dependent child. Audio files were transcribed into English and qualitatively coded using content analysis. RESULTS: Participants, most with breast cancer, ranged in age from 25 to 47. Five had considered the possibility of their own death from advanced cancer and three had previously discussed this with their children. While many expected their children would carry on well without them, seven expressed concern for the emotional/spiritual well-being of their children. Mothers anticipated physical and time-based parenting challenges but wanted the opportunity to focus on themselves and their children in advance of death. All but one would be willing to discuss an advance cancer diagnosis with dependent children; four expressed the value of doing so or the potential harm of abdicating this responsibility. CONCLUSIONS: If faced with an advanced cancer diagnosis, Mexican-American mothers are open to communicating with dependent children.

Phase Ib trial of IRX-2 plus durvalumab in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.

OBJECTIVES: IRX-2 is a multi-cytokine immune-activating agent with anti-tumor activity in non-metastatic head and neck squamous cell carcinoma (HNSCC). Here, we evaluated combined IRX-2 and durvalumab in patients with recurrent and/or metastatic HNSCC. MATERIALS AND METHODS: This was a phase Ib trial consisting of dose escalation and expansion. Primary endpoints were safety and biomarkers to assess the immune response in the tumor microenvironment including significant increases in PD-L1 expression and CD8 + tumor infiltrating lymphocytes (TIL) comparing pre- and on-treatment tumor biopsies. Secondary endpoints were objective response rates (ORR) and survival outcomes. RESULTS: Sixteen patients were evaluable for response, and nine patients were evaluable for biomarkers. Thirteen patients (68 %) had exposure to prior anti-PD-1 therapy. No dose-limiting or grade ≥ 3 treatment-related adverse events were observed. On-treatment biopsies showed significantly increased PD-L1 (p = 0.005), CD3+ (p = 0.020), CD4+ (p = 0.022), and CD8 + T cells (p = 0.017) compared to pre-treatment. Median overall survival and progression-free survival (PFS) were 6.18 months (95 % CI, 2.66-8.61) and 2.53 months (95 % CI, 1.81-4.04), respectively. One patient had an objective response (ORR, 5.3 %) with an ongoing PFS of > 25 months. Disease control rate was 42 %. The responder harbored an ARID1A variant of unknown significance (VUS) that was predicted to bind her HLA-I alleles with a higher affinity than the reference peptide. CONCLUSIONS: IRX-2 and durvalumab were safe and elicited the evidence of immune activation in the tumor microenvironment determined by increased PD-L1 expression and CD8+ TILs. CLINICAL TRIAL REGISTRATION NUMBER: NCT03381183.

Molecular characterization of the salivary adenoid cystic carcinoma immune landscape by anatomic subsites.

Adenoid cystic carcinoma (AdCC) is a slow-growing salivary gland malignancy that relapses frequently. AdCCs of the submandibular gland exhibit unique differences in prognosis and treatment response to adjuvant radiotherapy compared to other sites, yet the role of tumor anatomic subsite on gene expression and tumor immune microenvironment (TIME) composition remains unclear. We used 87 samples, including 48 samples (27 AdCC and 21 normal salivary gland tissue samples) from 4 publicly available AdCC RNA sequencing datasets, a validation set of 33 minor gland AdCCs, and 39 samples from an in-house cohort (30 AdCC and 9 normal salivary gland samples). RNA sequencing data were used for single sample gene set enrichment analysis and TIME deconvolution. Quantitative PCR and multiplex immunofluorescence were performed on the in-house cohort. Wilcoxon rank-sum, nonparametric equality-of-medians tests and linear regression models were used to evaluate tumor subsite differences. AdCCs of different anatomic subsites including parotid, submandibular, sublingual, and minor salivary glands differed with respect to expression of several key tumorigenic pathways. Among the three major salivary glands, the reactive oxygen species (ROS)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway signature was significantly underexpressed in AdCC of submandibular compared to parotid and sublingual glands while this association was not observed among normal glands. Additionally, the NRF2 pathway, whose expression was associated with favorable overall survival, was overexpressed in AdCCs of parotid gland compared to minor and submandibular glands. The TIME deconvolution identified differences in CD4+ T cell populations between AdCC of major and minor glands and natural killer (NK) cells among AdCC of minor, submandibular, and parotid glands while plasma cells were enriched in normal submandibular glands compared to other normal gland controls. Our data reveal key molecular differences in AdCC of different anatomic subsites. The ROS and NRF2 pathways are underexpressed in submandibular and minor AdCCs compared to parotid gland AdCCs, and NRF2 pathway expression is associated with favorable overall survival. The CD4+ T, NK, and plasma cell populations also vary by tumor subsites, suggesting that the observed submandibular AdCC tumor-intrinsic pathway differences may be responsible for influencing the TIME composition and survival differences.

Detecting HLA loss of heterozygosity within a standard diagnostic sequencing workflow for prognostic and therapeutic opportunities.

To enable interrogation of tumor HLA LOH as a clinical diagnostic for precision oncology, we developed and validated an assay that detects HLA LOH within the context of an FDA-approved clinical diagnostic test, Tempus xT CDx. Validation was conducted via: (1) analytical evaluation of 17 archival patient samples and 42 cell line admixtures and (2) independent clinical evaluation of LOH prevalence in the HLA-A gene (HLA-A LOH) across 10,982 patients. To evaluate the prognostic relevance of HLA-A LOH we assessed 256 immunotherapy-treated non-small cell lung cancer (NSCLC) patients. To determine the feasibility of prospectively identifying and enrolling HLA-A LOH patients into a clinical trial, we established BASECAMP-1 (NCT04981119). We observed a positive predictive agreement of 97% and a negative predictive agreement of 100% in samples with ≥ 40% tumor purity. We observed HLA-A LOH in 16.1% of patients (1771/10,982), comparable to previous reports. HLA-A LOH was associated with longer survival among NSCLC adenocarcinoma patients (HR = 0.60, 95% CI [0.37, 0.96], p = 0.032) with a trend towards shorter survival among squamous cell patients (HR = 1.64, 95% CI [0.80, 3.41], p = 0.183). In 20 months, we prospectively screened 1720 subjects using the Tempus AWARE program, identifying 26 HLA-A*02 LOH patients at 8 sites, with 14 (54%) enrolled into BASECAMP-1. In conclusion, we developed and validated an investigational assay that detects tumor HLA LOH within an FDA-approved clinical diagnostic test, enabling HLA LOH utilization in diagnostic, prognostic, and therapeutic applications.

Pembrolizumab and cabozantinib in recurrent and/or metastatic head and neck squamous cell carcinoma (RMHNSCC): long-term survival update with a biomarker analysis.

PURPOSE: Anti-programmed cell death protein 1 (PD-1) therapy is a standard of care in recurrent and/or metastatic head and neck squamous cell carcinoma (RMHNSCC). Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) have immunomodulatory properties and improve clinical outcomes in combination with anti-PD-1 therapy. We report the long-term efficacy and safety of pembrolizumab and cabozantinib and include a correlative biomarker analysis. PATIENTS AND METHODS: This open-label, single-arm, multicenter, phase 2 study screened 50 patients with RMHNSCC, of whom 36 received pembrolizumab and cabozantinib. Primary endpoint was overall response rate (ORR), safety, and tolerability. Secondary endpoints included progression free survival (PFS), overall survival (OS), and correlative studies of tissue and blood. We report the long-term PFS, OS, safety, and describe correlative biomarkers. RESULTS: With median follow-up of 22.4 months, median PFS was 12.8 months 2-year PFS of 32.6% (95%CI 18.8-56.3%) and median OS of 27.7 months,2-year OS of 54.7% (95%CI 38.9-76.8%). Median duration of response was 12.6 months, with 2-year rate of 38.5% (95%CI 30.8-81.8%). Long-term TRAEs included manageable hypothyroidism (5.5%) and grade 1 elevated AST and ALT (2.8%). Baseline tumor p-MET expression correlated with ORR (p=0.0055). Higher density of CD8+, CD103+, and CSF1-R+ cells at baseline correlated with improved OS (hazard ratio [HR]=5.27, p=0.030; HR =8.79, p=0.017; HR =6.87, p=0.040, respectively). CONCLUSION: Pembrolizumab and cabozantinib provided prolonged encouraging long-term disease control and survival with a maintained favorable safety profile. The prognostic significance of increased CD8+, CD103+ and CSF1-R+ cell density in TIME deserve further evaluation in similar clinical settings.

T Cell Responses to Individualized Neoantigen Therapy mRNA-4157 (V940) Alone or in Combination With Pembrolizumab in the Phase 1 KEYNOTE-603 Study.

mRNA-4157 (V940) is an individualized neoantigen therapy (INT) targeting up to 34 patient-specific tumor neoantigens to induce T cell responses and potentiate anti-tumor activity. We report mechanistic insights into the immunogenicity of mRNA-4157 via characterization of T cell responses to neoantigens from the first-in-human phase 1, KEYNOTE-603 study (NCT03313778) in patients with resected non-small cell lung cancer (Part A: 1mg mRNA-4157, n = 4) or resected cutaneous melanoma (Part D: 1mg mRNA-4157 + 200mg pembrolizumab, n = 12). Safety, tolerability, and immunogenicity were assessed. All patients experienced ≥1 treatment-emergent adverse event (AE); there were no grade 4/5 AEs or dose-limiting toxicities. mRNA-4157 alone induced consistent de novo, and strengthened pre-existing, T cell responses to targeted neoantigens. Following combination therapy, sustained mRNA-4157-induced neoantigen-specific T cell responses and expansion of cytotoxic CD8 and CD4 T cells were observed. These findings show the potential of a novel mRNA INT approach in oncology.

Demographic disparities in receipt of care at a comprehensive cancer center.

BACKGROUND: National Cancer Institute cancer centers (NCICCs) provide specialized cancer care including precision oncology and clinical treatment trials. While these centers can offer novel therapeutic options, less is known about when patients access these centers or at what timepoint in their disease course they receive specialized care. This is especially important since precision diagnostics and receipt of the optimal therapy upfront can impact patient outcomes and previous research suggests that access to these centers may vary by demographic characteristics. Here, we examine the timing of patients' presentation at Moffitt Cancer Center (MCC) relative to their initial diagnosis across several demographic characteristics. METHODS: A retrospective cohort study was conducted among patients who presented to MCC with breast, colon, lung, melanoma, and prostate cancers between December 2008 and April 2020. Patient demographic and clinical characteristics were obtained from the Moffitt Cancer Registry. The association between patient characteristics and the timing of patient presentation to MCC relative to the patient's cancer diagnosis was examined using logistic regression. RESULTS: Black patients (median days = 510) had a longer time between diagnosis and presentation to MCC compared to Whites (median days = 368). Black patients were also more likely to have received their initial cancer care outside of MCC compared to White patients (odds ratio [OR] and 95% confidence interval [CI] = 1.45 [1.32-1.60]). Furthermore, Hispanics were more likely to present to MCC at an advanced stage compared to non-Hispanic patients (OR [95% CI] = 1.28 [1.05-1.55]). CONCLUSIONS: We observed racial and ethnic differences in timing of receipt of care at MCC. Future studies should aim to identify contributing factors for the development of novel mitigation strategies and assess whether timing differences in referral to an NCICC correlate with long-term patient outcomes.

Psychosocial characteristics of patients undergoing cellular immunotherapies and their caregivers across time.

Chimeric antigen receptor T-cells and other immunotherapies have markedly changed the paradigm of treatment for patients with relapsed or refractory hematologic malignancies. While notable in efficacy, immunotherapy is characterized by a significant possibility of life-threatening side effects. Consequently, patients are often required to have informal family caregivers present and to stay near the treating center for several weeks after cell infusion. Further, the responsibility of managing a great deal of physical care and emotional support falls to these caregivers. Given the novelty of immunotherapy treatment, there is a need to better understand the psychosocial experience of patients receiving this treatment and their caregivers. This article describes the psychosocial characteristics of patients undergoing cellular immunotherapies and their caregivers across time, including patient/caregiver distress, coping, and caregiver burden and preparedness.

Monitoring Adverse Effects of Radiation Therapy in Patients With Head and Neck Cancer: The FACT-HN-RAD Patient-Reported Outcome Measure.

Importance: Patients undergoing radiation therapy (RT) for head and neck squamous cell carcinoma (HNSCC) experience a range of debilitating adverse effects (AEs). Patient-reported outcome (PRO) measures to quantify these AEs are a necessary and important component of health care; however, currently available PRO options often measure only disease-related symptoms or AEs of non-RT treatments. Objective: To develop a brief PRO measure of the most common AEs associated with RT for HNSCC. Design, Setting, and Participants: This was a qualitative study that followed the US Food and Drug Administration guidelines to develop a brief measure of patient-reported RT-related AEs (the Functional Assessment of Cancer Therapy-Head and Neck Radiotherapy [FACT-HN-RAD] measure). The study included (1) a literature review of clinical trials; (2) secondary analysis of retrospective concept elicitation interviews (CEIs); (3) electronic surveys of practicing radiation oncologists; (4) mapping of existing items to inform the development of the draft version of the measure; and (5) validation of content and face validity via patient cognitive interviews. Analysis was performed of CEI data and interviews with practicing radiation oncologists. Data analysis was conducted from July 1, 2022, to April 21, 2023. Exposures: Surveys and qualitative interviews. Main Outcomes and Measures: The most common patient-reported RT-related AEs among patients with HNSCC. Results: Of 19 CEI participants, 14 (mean [range] age, 67 [49-86] years; 12 [86%] men and 2 [14%] women) described RT-related AEs and were included in the secondary analysis. Eleven (79%) patients reported difficulty swallowing; 8 (57%), oral pain; 7 (50%), dry mouth; 7 (50%), weight loss; 6 (43%), skin burning; 5 (36%), loss of taste; 5 (36%), voice changes (36%); and 5 (36%), fatigue. Nine radiation oncologists (mean [range] time in practice, 8 [1-42] years; 5 [56%] men and 4 [44%] women) reported the most common AEs: 9 (100%) reported dysgeusia; 7 (78%), xerostomia; 7 (78%), mucositis or oral pain; 8 (89%), dysphagia or odynophagia; 6 (67%), dermatitis; and 3 (33%), fatigue. Together these data informed the development of an 8-item AE-focused measure of pain, dysphagia, xerostomia, dysgeusia, voice changes, dermatitis, fatigue, and weight loss. Cognitive interviews with 10 patients (mean [range] age, 61 [29-84] years; 8 [80%] men and 2 [20%] women) demonstrated strong face validity; all (100%) reported that the measure reflected their experience with RT and stated that the length of the questionnaire was "just right." Conclusions and Relevance: The 8-item FACT-HN-RAD measure captures the most common patient- and physician-reported AEs related to RT for HNSCC. This measure offers a means to serially monitor patient-reported treatment-related AEs and recovery over time in both clinical and research settings. Future work will evaluate the psychometric validity of the measure.

Phase 1 Dose Escalation of Stereotactic Body Radiation Therapy and Concurrent Cisplatin for Reirradiation of Unresectable, Recurrent Squamous Cell Carcinoma of the Head and Neck.

PURPOSE: Patients with locoregional recurrence of squamous cell carcinoma of the head and neck (SCCHN) have relatively poor outcomes; therefore, stereotactic body radiation therapy (SBRT) has been investigated for this patient population. We performed a phase 1 clinical trial to establish a maximum tolerated dose of SBRT with concurrent cisplatin in previously irradiated locoregional SCCHN. METHODS AND MATERIALS: Patients with recurrent SCCHN who had previously undergone radiation therapy to doses ≥45 Gy to the area of recurrence ≥6 months before enrollment and who were not surgical candidates or refused surgery were eligible. SBRT was delivered every other day for 5 fractions. Starting dose level was 6 Gy × 5 fractions, followed by 7 Gy × 5 fractions and 8 Gy × 5 fractions. Chemotherapy consisted of cisplatin given before every SBRT fraction at a dose of 15 mg/m2. Patients were monitored for dose-limiting toxicities (DLT) that occurred within 3 months from the start of SBRT. Secondary endpoints included locoregional failure, distant metastasis, and overall survival. RESULTS: Twenty patients were enrolled, with 18 patients evaluable for endpoints. One patient at dose level 1 (30 Gy) died of unknown causes 2 weeks following completion of treatment. Therefore, an additional 3 patients were accrued to the 30-Gy dose level, with no further DLTs observed. Three patients were then accrued at dose level 2 (35 Gy) and 9 patients at dose level 3 (40 Gy) without DLTs. At a median follow-up of 9.5 months, cumulative incidence of locoregional failure at 2 years was 61% (95% confidence interval [CI], 12%-66%), cumulative incidence of distant metastasis was 11% (95% CI, 74%-100%) at 2 years, and overall survival was 22% (95% CI, 9%-53%) at 2 years. CONCLUSIONS: Concurrent cisplatin and reirradiation with an SBRT dose of ≤40 Gy was safe and feasible in patients with locoregionally recurrent or second primary SCCHN.