Disparities in the Uptake of Telemedicine During the COVID-19 Surge in a Multidisciplinary Head and Neck Cancer Population by Patient Demographic Characteristics and Socioeconomic Status

This cohort study examines the association between patient demographic characteristics and socioeconomic status and engagement in telemedicine during the COVID-19 pandemic

Cetuximab and anemia prevention in head and neck cancer patients undergoing radiotherapy

BACKGROUND: Epidermal growth factor receptor (EGFR) activation is associated with increased production of interleukin 6 (IL6), which is intensified by radiotherapy (RT) induced inflammatory response. Elevated IL6 levels intensifies RT-induced anemia by upregulating hepcidin causing functional iron deficiency. Cetuximab, an EGFR inhibitor, has been associated with lower rates of anemia for locally advanced head and neck squamous cell carcinoma (HNSCC). We hypothesized that concomitant cetuximab could prevent RT-induced anemia. METHODS: We queried our institutional head and neck cancers database for non-metastatic HNSCC cases that received RT with concomitant cetuximab or RT-only between 2006 and 2018. Cetuximab was administered for some high-risk cases medically unfit for platinum agents per multidisciplinary team evaluation. We only included patients who had at least one complete blood count in the 4 months preceding and after RT. We compared the prevalence of anemia (defined as hemoglobin (Hb) below 12 g/dL in females and 13 g/dL in males) and mean Hb levels at baseline and after RT. Improvement of anemia/Hb (resolution of baseline anemia and/or an increase of baseline Hb ≥1 g/dL after RT), and overall survival (OS) in relation to anemia/Hb dynamics were also compared. RESULTS: A total of 171 patients were identified equally distributed between cetuximab-plus-RT and RT-only groups. The cetuximab-plus-RT group had more locally-advanced stage, oropharyngeal and high grade tumors (p \u3c 0.001 for all). Baseline anemia/Hb were similar, however anemia after RT conclusion was higher in the cetuximab-plus-RT vs RT-only (63.5% vs. 44.2%; p = 0.017), with a mean Hb of 11.98 g/dL vs. 12.9 g/dL; p = 0.003, for both respectively. This contributed to significantly worse anemia/Hb improvement for cetuximab-plus-RT (18.8% vs. 37.2%; p = 0.007). This effect was maintained after adjusting for other factors in multivariate analysis. The prevalence of iron, vitamin-B12 and folate deficiencies; and chronic kidney disease, was non-different. Baseline anemia was associated with worse OS (p = 0.0052) for the whole study cohort. Nevertheless, improvement of anemia/Hb was only marginally associated with better OS (p = 0.068). CONCLUSIONS: In contrast to previous studies, cetuximab was not associated with lower rates of anemia after RT for nonmetastatic HNSCC patients compared to RT-alone. Dedicated prospective studies are needed to elucidate the effect of cetuximab on RT-induced anemia

Assessing Oral Intake Outcomes in Head and Neck Cancer Patients Treated with Definitive Radiation with or Without Chemotherapy

Background: Head and neck cancer treatment modalities can significantly impact functional outcomes of patients, especially oral intake (Brizel, et al N Engl J Med 1998; Kamal, et al Support Care Cancer 2019). Radiation therapy in particular has been associated with posttreatment xerostomia and dysphagia (Adelstein, et al J Clin Oncol 2003; Hutcheson, et al Cancer 2013) which can affect quality of life and impair weight gain, contributing to worse long-term outcomes (Payakachat, et al Head Neck, 2013). Early speech-language pathology intervention has shown to be effective in improving these functional outcomes in this population (Greco, et al Int J Radiat Oncol Biol Phys 2018). Objectives: The purpose of this study is to evaluate oral intake outcomes of patients undergoing definitive radiation therapy with or without chemotherapy for head and neck squamous cell carcinoma. Methods: A cohort of patients with stage III or IV squamous cell carcinoma of the oropharynx, larynx, and hypopharynx treated with definitive radiation therapy with or without chemotherapy were extracted from system database. Patients with evidence of distant metastases were excluded. Swallow function was assessed both pre- and post-treatment (within four months of treatment initiation or conclusion) with the Functional Oral Intake Scale (FOIS) (Crary et al, Arch Phys Med Rehabil, 2005) as measured by a Speech-Language Pathologist (SLP) involved in the patient\u27s care. Body mass index (BMI) was evaluated within four months of treatment initiation and one year after treatment completion. The use of enteral feeding at one-year post-treatment was also assessed. Data was analyzed with descriptive statistical methods, Wilcoxon sign rank tests, and [chi]2d tests. Results: The sample included 152 patients. Table 1 highlights patient baseline characteristics, tumor location, and treatment. FOIS scores decreased from pre-treatment to post-treatment, with 75% of patients having a FOIS of 7 at pre-treatment compared with only 13.8% at the post-treatment time point (Table 1). Median BMI also decreased from pre-treatment to one-year post-treatment (Table 2). At one-year post-treatment, 23.7% patients (n=33) required enteral feeding. Conclusions: Definitive radiation therapy with or without chemotherapy in the treatment of head and neck cancer is associated with impaired oral intake. Treatment is also associated with decreases in BMI and longer use of enteral feeding, which may reflect sequelae of impaired oral intake. These factors have a negative impact on quality of life and can lead to long-term morbidity. Integrative treatment plans would therefore benefit from speech-language pathology interventions throughout the treatment process

Assessing Oral Intake Outcomes in Head and Neck Cancer Patients Treated with Definitive Radiation with or Without Chemotherapy

Background: Head and neck cancer treatment modalities can significantly impact functional outcomes of patients, especially oral intake (Brizel, et al N Engl J Med 1998; Kamal, et al Support Care Cancer 2019). Radiation therapy in particular has been associated with posttreatment xerostomia and dysphagia (Adelstein, et al J Clin Oncol 2003; Hutcheson, et al Cancer 2013) which can affect quality of life and impair weight gain, contributing to worse long-term outcomes (Payakachat, et al Head Neck, 2013). Early speech-language pathology intervention has shown to be effective in improving these functional outcomes in this population (Greco, et al Int J Radiat Oncol Biol Phys 2018). Objectives: The purpose of this study is to evaluate oral intake outcomes of patients undergoing definitive radiation therapy with or without chemotherapy for head and neck squamous cell carcinoma. Methods: A cohort of patients with stage III or IV squamous cell carcinoma of the oropharynx, larynx, and hypopharynx treated with definitive radiation therapy with or without chemotherapy were extracted from system database. Patients with evidence of distant metastases were excluded. Swallow function was assessed both pre- and post-treatment (within four months of treatment initiation or conclusion) with the Functional Oral Intake Scale (FOIS) (Crary et al, Arch Phys Med Rehabil, 2005) as measured by a Speech-Language Pathologist (SLP) involved in the patient\u27s care. Body mass index (BMI) was evaluated within four months of treatment initiation and one year after treatment completion. The use of enteral feeding at one-year post-treatment was also assessed. Data was analyzed with descriptive statistical methods, Wilcoxon sign rank tests, and [chi]2d tests. Results: The sample included 152 patients. Table 1 highlights patient baseline characteristics, tumor location, and treatment. FOIS scores decreased from pre-treatment to post-treatment, with 75% of patients having a FOIS of 7 at pre-treatment compared with only 13.8% at the post-treatment time point (Table 1). Median BMI also decreased from pre-treatment to one-year post-treatment (Table 2). At one-year post-treatment, 23.7% patients (n=33) required enteral feeding. Conclusions: Definitive radiation therapy with or without chemotherapy in the treatment of head and neck cancer is associated with impaired oral intake. Treatment is also associated with decreases in BMI and longer use of enteral feeding, which may reflect sequelae of impaired oral intake. These factors have a negative impact on quality of life and can lead to long-term morbidity. Integrative treatment plans would therefore benefit from speech-language pathology interventions throughout the treatment process

A differential response to cetuximab in patients with recurrent unresectable or metastatic head and neck cancer following immunotherapy (IO) exposure: An institutional experience

Background: Metastatic head and neck cancer is a diagnosis with poor prognosis and very little in terms of available active therapy. Until recently the mainstay of therapy was chemotherapy with or without cetuximab. The regimen of cetuximab (C), platinum (P) and 5FU has a response rate(RR) of 36% in the first line setting, and a PFS of 5.6 months and OS of 10.1 months. In the setting of post first line therapy immunotherapeutic agents (IO) have average RR of 15% and median OS of 8 months. Methods: We studied all patients with metastatic or recurrent head and neck cancer who were treated with an IO at our institution between May 2016 and July 2018 evaluating their entire history of therapy. 19 patient were treated with IO at our institution in the designated period of whom 9 received nivolumab (N) and 10 received pembrolizumab ( P ). Patients treated on trials were excluded. Patients who received less than 1 cycle of therapy were also excluded. 7 of the 19 patients received an IO in the first line setting after being refractory or resistant to platinum containing definitive therapy, 7 received the IO after a cetuximab (C) containing first line regimen, 1 patient received IO in second line but was naive to C and 4 received IO in the third line setting. Results: 3 of 19 patients treated with IO had partial response, there were no complete responses, 6 patients had stable disease as their best response and 10 patients progressed at the time of their first evaluation. 11 of 19 patients received additional therapy post IO. 10 patients received taxane based therapy 5 of whom the taxane was combined with C. Of the 5 patients who received a taxane and C combination 2 had CR, 2 had PR and one had PD. Of the 5 who received other taxane regimens, 1 had PR 1 had SD and 1 had PD, 2 expired prior to their first evaluation. The patient who received a non taxane regimen all had progressive disease. Of the 4 responding patients to C regimens 1 had SD during IO therapy and 3 had PD. The longest response duration to a C regimen post IO was 628 days. Conclusions: We observe an unusual response rate among patients treated with a combination of taxanes and cetuximab after IO therapy. This finding may relate to a modifying effect of IO on sensitivity to subsequent therapy. This observation merits further investigation

Does Cetuximab Reduce the Risk of Anemia in Patients Undergoing Radiation Therapy for Head and Neck Cancers?

Purpose/Objective(s): Epidermal growth factor receptor (EGFR) activation is associated with increased production of interleukin 6 (IL6), which is intensified by radiotherapy (RT) induced inflammatory response. Elevated IL6 levels promote RT-induced anemia by upregulating hepcidin causing functional iron deficiency. Cetuximab, an EGFR inhibitor, resulted in significantly lower rates of RT induced anemia for locally advanced head and neck squamous cell carcinoma (HNSCC) patients receiving definitive RT vs RT-alone according to Bonner et al; and other studies compared to concomitant chemotherapy. However, little is known for cases receiving cetuximab with RT in the adjuvant setting. Materials/Methods: We queried our institutional HNSCC database for surgically staged non-metastatic cases that received adjuvant RT with or without concomitant cetuximab between 2006-2018. Cetuximab was administered for some high-risk cases medically unfit for platinum agents per multidisciplinary team evaluation. All included patients need to have at least one complete blood count pre- and post-RT end. We compared RT-cetuximab vs RT-alone for prevalence of baseline and post-RT anemia, defined as Hb below 12g/dL in females and 13g/dL in males, and mean hemoglobin (Hb) levels. We also assessed the improvement in Hb level post-RT (resolution of baseline anemia or Hb increase of at least 1g/dL above baseline), in addition to overall survival (OS) in relation to anemia/Hb dynamics. Results: We were able to identify 66 patients who fit our inclusion criteria, of which 27 (41%) received RT-cetuximab, with the remaining receiving RT-alone (n=39, 59%). Median age was 62.5 years (range, 34-88 years), males 80%, black 29%, and 85% had a smoking history. The majority of cases (73%) were locally advanced. Oral cavity and oropharynx were the most common subsites (37.5% each), with HPV+ve cases representing 52% of the later. The study groups were well-balanced, except for higher rates of positive final surgical margins, and extracapsular space invasion and median RT dose (p\u3c0.05). Baseline anemia was diagnosed in 70.4% in RT-cetuximab vs 76.9% in the RT-alone, p=0.76; with similar mean Hb level (11.7g/dL in both). Meanwhile, baseline iron, vitamin-B12 and folate deficiencies, and chronic kidney disease were non-different. After completion of RT, mean Hb was significantly higher in the RT-alone (12.9±1.4 g/dL) compared to RT-Cetuximab (11.9±2.1 g/dL), p=0.02. Nevertheless, higher anemia levels (70% vs 51%) and lower improvement of Hb post-RT (81.5% vs 92.3%) were both non-significant for RT-cetuximab vs RT-alone respectively, p\u3e0.05 for both. On multivariate analysis, baseline anemia was associated with worse OS (p=0.0052), unlike improvement of Hb post-RT (p=0.14) with a corresponding better improvement of Hb (56.4% vs. 25.9%, p=0.014), albeit lower anemia levels (70% vs. 51%), was non significant (p=0.195). On multivariate analysis, lack of baseline anemia was associated with better OS (p=0.0052), whereas improvement of Hb post-RT was only marginal (p=0.068). Conclusion: In a homogenous cohort of HNSCC patients treated postoperatively, concomitant cetuximab was not associated with lower RT-induced anemia, in contrast to previous studies

Randomized Phase III, Double-Blind, Placebo-Controlled Study of Prophylactic Gabapentin for the Reduction of Radiation Therapy-Induced Pain During the Treatment of Oropharyngeal Squamous Cell Carcinoma

Purpose/Objective(s): We sought to determine if prophylactic gabapentin usage in patients undergoing definitive concurrent chemoradiotherapy (chemoRT) for oropharyngeal cancer improves patient-reported quality of life (QOL) metrics, opioid analgesic requirements, and feeding tube (FT) placement. Materials/Methods: This double-blind, randomized phase III study for patients with AJCC 7th ed stage III-IV oropharyngeal squamous cell carcinoma undergoing concurrent chemoRT randomly allocated patients to prophylactic gabapentin (600 mg TID) or placebo, stratified by smoking status. All patients received 70 Gy in 35 fx using IMRT. The primary endpoint was change in Patient-Reported Oral Mucositis Symptom (PROMS) scores from baseline over the study period. Opioid requirements (average over the entire study period and change from baseline, converted to daily morphine equivalents [DME]), FT placement, and other patient-reported QOL metrics (FACT-HN and PRO-CTCAE) were assessed. Questionnaires were administered at baseline, weekly during RT treatments, and at 6-week post-RT follow-up (f/u). Patients were considered compliant if they took at least 12 doses in any given week (self-reported). Repeated measures ANOVA was used to detect differences in PROMS scores and change in opioid use from baseline. Wilcoxon-rank sum tests were used to compare average opioid use, FACT-HN, and PRO-CTCAE scores. Chi-square test was used to compare FT placement. A P value less than 0.05 was considered statistically significant. Results: There were 65 patients enrolled in the study and 7 withdrew consent, leaving 58 patients to be analyzed. Baseline characteristics were well-balanced, and only 1 patient was considered non-compliant. All patients completed RT as planned. No significant difference was found in PROMS scores between the two groups (P = 0.130). FT placement was significantly higher in the gabapentin vs placebo arm (64.3% vs 33.3%, P = 0.003). Of the FTs placed, 96% were Dobhoff tubes. There was no significant difference in terms of average opioid use (median 22.8 DME [IQR 12.8-36.5] vs 15.8 DME [IQR 8.3-32.4], P = 0.412) or change in opioid use (P = 0.818) for gabapentin vs placebo, respectively. For the FACT-HN questionnaire, the only significant difference noted was in the functional well-being index with the gabapentin arm having a significant decrease in scores from baseline to f/u (median -6 [IQR -10 to -1.5] vs -1 [IQR -5.75 to 5], P = 0.017) with lower scores suggesting poorer QOL. PRO-CTCAE scores increased significantly at f/u from baseline for gabapentin vs placebo (median 6 [IQR 3 to 11] vs 1 [IQR -2 to 6.5], P = 0.014) with higher scores suggesting worse QOL. Conclusion: This study suggests that prophylactic gabapentin is not effective in improving pain related to mucositis during chemoRT in patients with oropharyngeal squamous cell carcinoma, and other strategies should be evaluated to minimize opioid usage in this patient population

Randomized Phase III, Double-Blind, Placebo-Controlled Study of Prophylactic Gabapentin for the Reduction of Radiation Therapy-Induced Pain During the Treatment of Oropharyngeal Squamous Cell Carcinoma

Purpose/Objective(s): We sought to determine if prophylactic gabapentin usage in patients undergoing definitive concurrent chemoradiotherapy (chemoRT) for oropharyngeal cancer improves patient-reported quality of life (QOL) metrics, opioid analgesic requirements, and feeding tube (FT) placement. Materials/Methods: This double-blind, randomized phase III study for patients with AJCC 7th ed stage III-IV oropharyngeal squamous cell carcinoma undergoing concurrent chemoRT randomly allocated patients to prophylactic gabapentin (600 mg TID) or placebo, stratified by smoking status. All patients received 70 Gy in 35 fx using IMRT. The primary endpoint was change in Patient-Reported Oral Mucositis Symptom (PROMS) scores from baseline over the study period. Opioid requirements (average over the entire study period and change from baseline, converted to daily morphine equivalents [DME]), FT placement, and other patient-reported QOL metrics (FACT-HN and PRO-CTCAE) were assessed. Questionnaires were administered at baseline, weekly during RT treatments, and at 6-week post-RT follow-up (f/u). Patients were considered compliant if they took at least 12 doses in any given week (self-reported). Repeated measures ANOVA was used to detect differences in PROMS scores and change in opioid use from baseline. Wilcoxon-rank sum tests were used to compare average opioid use, FACT-HN, and PRO-CTCAE scores. Chi-square test was used to compare FT placement. A P value less than 0.05 was considered statistically significant. Results: There were 65 patients enrolled in the study and 7 withdrew consent, leaving 58 patients to be analyzed. Baseline characteristics were well-balanced, and only 1 patient was considered non-compliant. All patients completed RT as planned. No significant difference was found in PROMS scores between the two groups (P = 0.130). FT placement was significantly higher in the gabapentin vs placebo arm (64.3% vs 33.3%, P = 0.003). Of the FTs placed, 96% were Dobhoff tubes. There was no significant difference in terms of average opioid use (median 22.8 DME [IQR 12.8-36.5] vs 15.8 DME [IQR 8.3-32.4], P = 0.412) or change in opioid use (P = 0.818) for gabapentin vs placebo, respectively. For the FACT-HN questionnaire, the only significant difference noted was in the functional well-being index with the gabapentin arm having a significant decrease in scores from baseline to f/u (median -6 [IQR -10 to -1.5] vs -1 [IQR -5.75 to 5], P = 0.017) with lower scores suggesting poorer QOL. PRO-CTCAE scores increased significantly at f/u from baseline for gabapentin vs placebo (median 6 [IQR 3 to 11] vs 1 [IQR -2 to 6.5], P = 0.014) with higher scores suggesting worse QOL. Conclusion: This study suggests that prophylactic gabapentin is not effective in improving pain related to mucositis during chemoRT in patients with oropharyngeal squamous cell carcinoma, and other strategies should be evaluated to minimize opioid usage in this patient population